Search results for: toxicity studies

Authors: Hakima Althalb

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Petroleum contamination of sandy soils is a severe environmental problem in Libya, but relatively little work has been carried out to optimize the bioremediation of such heavily contaminated soil, particularly at a pilot scale. The purpose of this research was to determine the potential for the microbial-based bioremediation of hydrocarbon-contaminated soil obtained from an oil refinery in Libya and to assess the potential of both ozonation and phytoremediation (both applied after initial bioremediation) to reduce residual hydrocarbon levels. Plots containing 500 kg soil (triplicates) (contaminated soil diluted with clean soil 50% volume) were set up, (designated as Land Treatment Units; LTUs) containing five different nutrient levels and mixtures (Urea + NPK (nitrogen; phosphor; potassium) mixtures) to obtain C:N:P ratios 100:10:1, and monitored for 90 days. Hydrocarbon levels, microbial numbers, and toxicity (EC50 using luminescent microbial based tests) were assessed. Hydrocarbon levels in non-diluted and diluted soil ranged from 20 733-22 366 mg/kg and from 16 000-17 000 mg/kg respectively. Although all the land treatment units revealed a significant hydrocarbon reduction over time, the highest reduction in hydrocarbon levels obtained was around 60%. For example, 63% hydrocarbon removal was observed using a mixture of urea and NPK with a C:N:P ratio of 100:10:1). Soil toxicity (as assessed using luminescence based toxicity assays) reduced in line with the reduction in total petroleum hydrocarbons observed. However, as relatively high residual TPH (total petroleum hydrocarbon) levels (ranging from 6033-14166mg/kg) were still present after initial bioremediation two ‘post-treatments’ (phytoremediation and ozonation) were attempted to remove residual hydrocarbons remaining. Five locally grown (agriculturally important) plant species were tested. The germination of all plants examined was strongly inhibited (80-100%) and seedlings failed to grow well in the contaminated soil, indicating that the previously bioremediated soils were still toxic to the plants. Subsequent ozonation followed by another bioremediation of soil was more successful than phytoremediation. But even the most promising successful treatment in this study (ozonation for 6 hours at 25ppm followed by bioremediation) still only removed approximately 31% of the residual hydrocarbons. Overall, this work showed that the bioremediation of such highly contaminated soils is difficult and that a combination of treatments would be required to achieve successful remediation. Even after initial dilution and bioremediation the soils remained toxic to plant growth and were therefore not suitable for phytoremediation.

Keywords: bioremediation, petroleum hydrocarbons, ozone, phytoremediation

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Authors: Anjana Aggarwal, Sheilja Walia

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Prevalence of obesity and overweight is increasing due to sedentary lifestyles and busy schedules of people that spend less time on physical exercise. To reduce weight, people are finding easier and more convenient ways. The easiest solution is the use of dietary supplements and fat burners. These are products that decrease body weight by increasing the basal metabolic rate. Various reports have been published on the consumption of fat burners leading to heart palpitations, seizures, anxiety, depression, psychosis, bradycardia, insomnia, muscle contractions, hepatotoxicity, and even liver failure. Case reports and series are reporting that the ingredients present in the fat burners caused acute liver failure (ALF) and hepatic toxicity in many cases. Another contributing factor is the absence of regulations from the Food and Drug Administration on these products, leading to increased consumption and a higher risk of liver diseases among the population. This systematic review aims to attain a better understanding of the dietary supplements used globally to reduce weight and document the case reports/series of acute liver failure caused by the consumption of fat burners. Electronic databases like PubMed, Cochrane, Google Scholar, etc., will be systematically searched for relevant articles. Various websites of dietary products and brands that sell such supplements, Journals of Hepatology, National and international projects launched for ALF, and their reports, along with the review of grey literature, will also be done to get a better understanding of the topic. After discussing with the co-author, the selection and screening of the articles will be performed by the author. The studies will be selected based on the predefined inclusion and exclusion criteria. The case reports and case series that will be included in the final list of the studies will be assessed for methodological quality using the CARE guidelines. The results from this study will provide insights and a better understanding of fat burners. Since the supplements are easily available in the market without any restrictions on their sale, people are unaware of their adverse effects. The consumption of these supplements causes acute liver failure. Thus, this review will provide a platform for future larger studies to be conducted.

Keywords: acute liver failure, dietary supplements, fat burners, weight loss supplements

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Authors: Chikang Wang, Jhongjheng Jian, Poming Huang

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Among a wide variety of pharmaceutical compounds, tetracycline antibiotics are one of the largest groups of pharmaceutical compounds extensively used in human and veterinary medicine to treat and prevent bacterial infections. Because it is water soluble, biologically active, stable and bio-refractory, release to the environment threatens aquatic life and increases the risk posed by antibiotic-resistant pathogens. In practice, due to its antibacterial nature, tetracycline cannot be effectively destructed by traditional biological methods. Hence, in this study, two advanced oxidation processes such as ozonation and sono-Fenton processes were conducted individually to degrade the tetracycline for investigating their feasibility on tetracycline degradation. Effect of operational variables on tetracycline degradation, release of nitrogen and change of toxicity were also proposed. Initial tetracycline concentration was 50 mg/L. To evaluate the efficiency of tetracycline degradation by ozonation, the ozone gas was produced by an ozone generator (Model LAB2B, Ozonia) and introduced into the reactor with different flows (25 - 500 mL/min) at varying pH levels (pH 3 - pH 11) and reaction temperatures (15 - 55°C). In sono-Fenton system, an ultrasonic transducer (Microson VCX 750, USA) operated at 20 kHz combined with H₂O₂ (2 mM) and Fe²⁺ (0.2 mM) were carried out at different pH levels (pH 3 - pH 11), aeration gas and flows (air and oxygen; 0.2 - 1.0 L/min), tetracycline concentrations (10 - 200 mg/L), reaction temperatures (15 - 55°C) and ultrasonic powers (25 - 200 Watts), respectively. Sole ultrasound was ineffective on tetracycline degradation, where the degradation efficiencies were lower than 10% with 60 min reaction. Contribution of Fe²⁺ and H₂O₂ on the degradation of tetracycline was significant, where the maximum tetracycline degradation efficiency in sono-Fenton process was as high as 91.3% followed by 45.8% mineralization. Effect of initial pH level on tetracycline degradation was insignificant from pH 3 to pH 6 but significantly decreased as the pH was greater than pH 7. Increase of the ultrasonic power was slightly increased the degradation efficiency of tetracycline, which indicated that the hydroxyl radicals dominated the oxidation of tetracycline. Effects of aeration of air or oxygen with different flows and reaction temperatures were insignificant. Ozonation showed better efficiencies in tetracycline degradation, where the optimum reaction condition was found at pH 3, 100 mL O₃/min and 25°C with 94% degradation and 60% mineralization. The toxicity of tetracycline was significantly decreased due to the mineralization of tetracycline. In addition, less than 10% of nitrogen content was released to solution phase as NH₃-N, and the most degraded tetracycline cannot be full mineralized to CO₂. The results shown in this study indicated that both the sono-Fenton process and ozonation can effectively degrade the tetracycline and reduce its toxicity at profitable condition. The costs of two systems needed to be further investigated to understand the feasibility in tetracycline degradation.

Keywords: degradation, detoxification, mineralization, ozonation, sono-Fenton process, tetracycline

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Authors: Dagikhudo Dagiev

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This paper is a thorough contribution to the analysis of Russian, Soviet and post-Soviet scholarship on the study of Ismailism in Central Asia. It focuses on the lengthy development of Russian studies on Ismailism from the Russian colonial domination to the entire period of Soviet rule, down to the collapse of the Soviet Union and the last two decades of post-Soviet history. These studies, conducted along the lines of various disciplines in the span of more than one hundred years, have resulted in a large amount of scholarly contributions. This paper aims at probing the virtues and shortcoming of such scholarship. Particularly, our investigation of the specialised fields in the Russian-Soviet Studies has required laborious researches in Russian and Central Asian libraries, which have enabled us to provide a guide through this literature, assessing its ideological leanings and qualities, institutions and level of scholarship. Despite some shortcomings, due to Marxism and the authoritarian rule of the Communist Party over the socio-religious life of the people and religious communities, Soviet studies have produced many positive insights on Ismailis studies. These captured almost every aspects of the life of the Ismaili community from anthropology to archaeology, ethnography, history, philosophy, ritual practice and, most importantly, collection and preservation of Ismaiili manuscripts, which will be examined and assessed in this study.

Keywords: Central Asian Studies, Ismailism, Russian Studies, Soviet Studies

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Authors: Inna Kornienko, Svetlana Guryeva, Natalia Danilova, Elena Petersen

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Drug toxicity often goes undetected until clinical trials, the most expensive and dangerous phase of drug development. Both human cell culture and animal studies have limitations that cannot be overcome by improvements in drug testing protocols. Tissue engineering is an emerging alternative approach to creating models of human malignant tumors for experimental oncology, personalized medicine, and drug discovery studies. This new generation of bioengineered tumors provides an opportunity to control and explore the role of every component of the model system including cell populations, supportive scaffolds, and signaling molecules. An area that could greatly benefit from these models is cancer research. Recent advances in tissue engineering demonstrated that decellularized tissue is an excellent scaffold for tissue engineering. Decellularization of donor organs such as heart, liver, and lung can provide an acellular, naturally occurring three-dimensional biologic scaffold material that can then be seeded with selected cell populations. Preliminary studies in animal models have provided encouraging results for the proof of concept. Decellularized Organs preserve organ microenvironment, which is critical for cancer metastasis. Utilizing 3D tumor models results greater proximity of cell culture morphological characteristics in a model to its in vivo counterpart, allows more accurate simulation of the processes within a functioning tumor and its pathogenesis. 3D models allow study of migration processes and cell proliferation with higher reliability as well. Moreover, cancer cells in a 3D model bear closer resemblance to living conditions in terms of gene expression, cell surface receptor expression, and signaling. 2D cell monolayers do not provide the geometrical and mechanical cues of tissues in vivo and are, therefore, not suitable to accurately predict the responses of living organisms. 3D models can provide several levels of complexity from simple monocultures of cancer cell lines in liquid environment comprised of oxygen and nutrient gradients and cell-cell interaction to more advanced models, which include co-culturing with other cell types, such as endothelial and immune cells. Following this reasoning, spheroids cultivated from one or multiple patient-derived cell lines can be utilized to seed the matrix rather than monolayer cells. This approach furthers the progress towards personalized medicine. As an initial step to create a new ex vivo tissue engineered model of a cancer tumor, optimized protocols have been designed to obtain organ-specific acellular matrices and evaluate their potential as tissue engineered scaffolds for cultures of normal and tumor cells. Decellularized biomatrix was prepared from animals’ kidneys, urethra, lungs, heart, and liver by two decellularization methods: perfusion in a bioreactor system and immersion-agitation on an orbital shaker with the use of various detergents (SDS, Triton X-100) in different concentrations and freezing. Acellular scaffolds and tissue engineered constructs have been characterized and compared using morphological methods. Models using decellularized matrix have certain advantages, such as maintaining native extracellular matrix properties and biomimetic microenvironment for cancer cells; compatibility with multiple cell types for cell culture and drug screening; utilization to culture patient-derived cells in vitro to evaluate different anticancer therapeutics for developing personalized medicines.

Keywords: 3D models, decellularization, drug discovery, drug toxicity, scaffolds, spheroids, tissue engineering

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Authors: K. Rasool

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Sulfate-reducing bacteria (SRBs) induced biofilm formation is a global industrial concern due to its role in the development of microbial-induced corrosion (MIC). Herein, we have developed a biodegradable chitosan/lignosulfonate nanocomposite (CS@LS) as an efficient green biocide for the inhibition of SRBs biofilms. We investigated in detail the inhibition mechanism of SRBs by CS@LS in seawater media. Stable CS@LS-1:1 with 150–200 nm average size and zeta potential of + 34.25 mV was synthesized. The biocidal performance of CS@LS was evaluated by sulfate reduction profiles coupled with analysis of extracted extracellular polymeric substances (EPS) and lactate dehydrogenase (LDH) release assays. As the nanocomposite concentration was increased from 50 to 500 µg/mL, the specific sulfate reduction rate (SSRR) decreased from 0.278 to 0.036 g-sulfate/g-VSS*day showing a relative sulfate reduction inhibition of 86.64% as compared to that of control. Similarly, the specific organic uptake rate (SOUR) decreased from 0.082 to 0.039 0.036 g-TOC/g-VSS*day giving a relative co-substrate oxidation inhibition of 52.19% as compared to that of control. The SRBs spiked with 500 µg/mL CS@LS showed a reduction in cell viability to 1.5 × 106 MPN/mL. To assess the biosafety of the nanocomposite on the marine biota, the 72-hours acute toxicity assays using the zebrafish embryo model revealed that the LC50 for the CS@LS was 103.3 µg/mL. Thus, CS@LS can be classified as environmentally friendly. The nanocomposite showed long-term stability and excellent antibacterial properties against SRBs growth and is thus potentially useful for combating the problems of biofilm growth in harsh marine and aquatic environments.

Keywords: green biocides, chitosan/lignosulfonate nanocomposite, SRBs, toxicity

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Authors: Wilfred A. Abiaa, Chibundu N. Ezekiel, Benedikt Warth, Michael Sulyok, Paul C. Turner, Rudolf Krska, Paul F. Moundipa

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Mycotoxins are a wide range of toxic secondary metabolites of fungi that contaminate various food commodities worldwide especially in sub-Saharan Africa (SSA). Such contamination seriously compromises food safety and quality posing a serious problem for human health as well as to trade and the economy. Their concentrations depend on various factors, such as the commodity itself, climatic conditions, storage conditions, seasonal variances, and processing methods. When humans consume foods contaminated by mycotoxins, they exert toxic effects to their health through various modes of actions. Rural populations in sub-Saharan Africa, are exposed to dietary mycotoxins, but it is supposed that exposure levels and health risks associated with mycotoxins between SSA countries may vary. Dietary exposures and health risk assessment studies have been limited by lack of equipment for the proper assessment of the associated health implications on consumer populations when they eat contaminated agricultural products. As such, mycotoxin research is premature in several SSA nations with product evaluation for mycotoxin loads below/above legislative limits being inadequate. Few nations have health risk assessment reports mainly based on direct quantification of the toxins in foods ('external exposure') and linking food levels with data from food frequency questionnaires. Nonetheless, the assessment of the exposure and health risk to mycotoxins requires more than the traditional approaches. Only a fraction of the mycotoxins in contaminated foods reaches the blood stream and exert toxicity ('internal exposure'). Also, internal exposure is usually smaller than external exposure thus dependence on external exposure alone may induce confounders in risk assessment. Some studies from SSA earlier focused on biomarker analysis mainly on aflatoxins while a few recent studies have concentrated on the multi-biomarker analysis of exposures in urine providing probable associations between observed disease occurrences and dietary mycotoxins levels. As a result, new techniques that could assess the levels of exposures directly in body tissue or fluid, and possibly link them to the disease state of individuals became urgent.

Keywords: mycotoxins, biomarkers, exposure assessment, health risk assessment, sub-Saharan Africa

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Authors: Haile Nega Mulata, Seifu Daniel, Umeta Melaku, Wendwesson Ergete, Natesan Gnanasekaran

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Background: In Ethiopia, medicinal plants have been used for various human and animal diseases. In this study, we have examined the potential effect of hydroethanolic extract of Calpurnia aurea seed against hepatotoxicity and haematotoxicity induced by Highly Active Antiretroviral Therapy (HAART) drugs in Albino Wistar rats. Methods: We collected Matured dried seeds of Calpurnia aurea from northern Ethiopia (south Tigray and south Gondar) in June 2013. The powder of the dried seed sample was macerated with 70% ethanol and dried using rotavapor. We have investigated the Preliminary phytochemical tests and in-vitro antioxidant properties. Then, we induced toxicity with HAART drugs and gave the experimental animals different doses of the crude extract orally for thirty-five days. On the 35th day, the animals were fasted overnight and sacrificed by cervical dislocation. We collected the blood samples by cardiac puncture. We excised the liver and brain tissues for further histopathological studies. Subsequently, we analysed serum levels of the liver enzymes- Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase, Total Bilirubin, and Serum Albumin, using commercial kits in Cobas Integra 400 Plus Roche Analyzer Germany. We have also assessed the haematological profile using an automated haematology Analyser (Sysmex KX-2IN). Results: A significant (P<0.05) decrease in serum enzymes (ALT and AST) and total bilirubin were observed in groups that received the highest dose (300mg/kg) of the seed extract. And significant (P<0.05) elevation of total red blood cell count, haemoglobin, and hematocrit percentage was observed in the groups that received the seed extract compared to the HAART-treated groups. The WBC count mean values showed a statistically significant increase (p<0.05) in groups that received HAART and 200 and 300mg/kg extract, respectively. The histopathological observations also showed that the oral administration of varying doses of the crude extract of the seed reversed to a normal state. Conclusion: The hydroethanolic extract of the Calpurnia aurea seed lowered the hepatotoxicity and haematotoxicity in a dose-dependent manner. The antioxidant properties of the Calpurnia aurea seed extract may have possible protective effects against the drug's toxicity.

Keywords: calpurnia aurea, hepatotoxicity, haematotoxicity, antioxidant, histopathology, HAART

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Authors: Nasrin Hosseinzad, Ramin Ghasemi Shayan

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Chemotherapy is the most common procedure in the treatment of advanced cancers but is justsoberlyoperativeand toxic. Nevertheless, the efficiency of chemotherapy is restrictedowing to multiple drug resistance(MDR). Lately, plentiful preclinical experiments have revealedthatPaclitaxel-Curcumin could be an ultimateapproach to converse MDR and synergistically increase their efficiency. The connotationsamongst B-cell-lymphoma2(BCL-2) and multi-drug-resistance-associated-P-glycoprotein(MDR1) consequence of patients forecast the efficiency of paclitaxel-built chemoradiotherapy. There are evidences of the efficacy of paclitaxel in the treatment of surface-transmission of bladder-cell-carcinoma by manipulating bio-adhesive microspheres accomplishedthroughout measured release of drug at urine epithelium. In Genetically-Modified method, muco-adhesive oily constructionoftricaprylin, Tween 80, and paclitaxel group showed slighter toxicity than control in therapeutic dose. Postoperative chemotherapy-Paclitaxel might be more advantageous for survival than adjuvant chemo-radio-therapy, and coulddiminish postoperative complications in cervical cancer patients underwent a radical hysterectomy.HA-Se-PTX(Hyaluronic acid, Selenium, Paclitaxel) nanoparticles could observablyconstrain the proliferation, transmission, and invasion of metastatic cells and apoptosis. Furthermore, they exhibitedvast in vivo anti-tumor effect. Additionally, HA-Se-PTX displayedminor toxicity on mice-chef-organs. Briefly, HA-Se-PTX mightprogress into a respectednano-scale agentinrespiratory cancers. To sum up, Paclitaxel is considered a profitable anti-cancer drug in the treatment and anti-progress symptoms in malignant cancers.

Keywords: cancer, paclitaxel, chemotherapy, tumor

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Authors: Dilek Ozturk, Narin Ozturk, Zeliha Pala Kara, Engin Kaptan, Serap Sancar Bas, Nurten Ozsoy, Alper Okyar

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Most physiological processes oscillate in a rhythmic manner in mammals including metabolism and energy homeostasis, locomotor activity, hormone secretion, immune and endocrine system functions. Endocrine body rhythms are tightly regulated by the circadian timing system. The hypothalamic-pituitary-thyroid (HPT) axis is under circadian control at multiple levels from hypothalamus to thyroid gland. Since circadian timing system controls a variety of biological functions in mammals, circadian rhythms of biological functions may modify the drug tolerability/toxicity depending on the dosing time. Selective mTOR (mammalian target of rapamycin) inhibitor everolimus is an immunosuppressant and anticancer agent that is active against many cancers. It was also found to be active in medullary thyroid cancer. The aim of this study was to investigate the dosing time-dependent toxicity of everolimus on the thyroid gland and hormones in mice. Healthy C57BL/6J mice were synchronized with 12h:12h Light-Dark cycle (LD12:12, with Zeitgeber Time 0 – ZT0 – corresponding to Light onset). Everolimus was administered to male (5 mg/kg/day) and female mice (15 mg/kg/day) orally at ZT1-rest period- and ZT13-activity period- for 4 weeks; body weight loss, clinical signs and possible changes in serum thyroid hormone levels (TSH and free T4) were examined. Histological alterations in the thyroid gland were evaluated according to the following criteria: follicular size, colloid density and viscidity, height of the follicular epithelium and the presence of necrotic cells. The statistical significance between differences was analyzed with ANOVA. Study findings included everolimus-related diarrhea, decreased activity, decreased body weight gains, alterations in serum TSH levels, and histopathological changes in thyroid gland. Decreases in mean body weight gains were more evident in mice treated at ZT1 as compared to ZT13 (p < 0.001, for both sexes). Control tissue sections of thyroid glands exhibited well-organized histoarchitecture when compared to everolimus-treated groups. Everolimus caused histopathological alterations in thyroid glands in male (5 mg/kg, slightly) and female mice (15 mg/kg; p < 0.01 for both ZT as compared to their controls) irrespective of dosing-time. TSH levels were slightly decreased upon everolimus treatment at ZT13 in both males and females. Conversely, increases in TSH levels were observed when everolimus treated at ZT1 in both males (5 mg/kg; p < 0.05) and females (15 mg/kg; slightly). No statistically significant alterations in serum free T4 levels were observed. TSH and free T4 is clinically important thyroid hormones since a number of disease states have been linked to alterations in these hormones. Serum free T4 levels within the normal ranges in the presence of abnormal serum TSH levels in everolimus treated mice may suggest subclinical thyroid disease which may have repercussions on the cardiovascular system, as well as on other organs and systems. Our study has revealed the histological damage on thyroid gland induced by subacute everolimus administration, this effect was irrespective of dosing time. However, based on the body weight changes and clinical signs upon everolimus treatment, tolerability for the drug was best following dosing at ZT13 in both male and females. Yet, effects of everolimus on thyroid functions may deserve further studies regarding their clinical importance and chronotoxicity.

Keywords: circadian rhythm, chronotoxicity, everolimus, thyroid gland, thyroid hormones

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Authors: Nesrine Benarous, Hassiba Bougueria, Nabila Moussa Slimane, Aouatef Cherouana

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Crystal polymorphism is important for the synthesis of more potent and bioactive pharmaceutical compounds, including their different properties, such as packing arrangement and conformation. In fact, polymorphism plays a vital role in drug development. Different parameters affect the crystallization and give their degree of freedom. Severalproperties affected polymorphism, like kinetics, thermodynamics, spectroscopy, and mechanical property. Various techniques are used for characterizing polymorphs, are crystallography, morphology, phase transitions, molecular motion, and chemical environment. In this work, crystal structures of two polymorphs (I and II) of the Schiff base (SB) title compound were prepared by condensation reaction. The crystal structures of both polymorphs were determined by single X-ray analysis. The two polymorphs crystallize in two different space groups: P21/c for I and Pbca for II. The dihedral angles between the two phenyl rings are 4.81º for I and 82.27º for II. Both crystal structures are built on the basis of moderate and weak hydrogen bonds, 𝜋-stacking, and halogen⋯halogeninteractions. On the other hand, Hirshfeld surface (HS) analysis indicates that the most important contributions to the crystal packing for the two polymorphs are from Cl⋯H/H⋯Cl, H⋯H, and N⋯H/H⋯N contacts. These are followed by C⋯H/H⋯C for compound I and C⋯C and by C⋯H/H⋯C contacts for compound II. Afterwards, the in vitro antibacterial activity revealed that the SB have been found effective against G- bacteria Klebsiella pneumonia andG+ bacteria Staphylococcus aureuswith MIC value of14.37μg/mL. Moreover, the SBexhibited moderate toxicity against Brine Shrimp with LC50 value of 44.19μg/mL.

Keywords: polymorph, crystal structure, hirshfeld surface analysis, in vitro antibacterial activity, toxicity

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Authors: Walaa G. Hozayen, Osama M. Ahmed, Haidy T. Abo Sree

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The clinical usefulness of anthracycline antineoplastic antibiotic, doxorubicin (DOX) is restricted since it has several acute and chronic side effects. The effect of doxorubicin (4 mg/kg b.w/week) without or with oral administration of purslane (Portulaca oleracea) shoot ethanolic extract (50mg/kg b.w./day) and purslane seed ethanolic extract (50mg/kg b.w./day) co-treatments for 6 weeks was evaluated in adult male rats. Serum testosterone luteinizing hormone (LH), follicle stimulating hormone (FSH) level were assayed. Testis lipid peroxidation (indexed by MDA) and antioxidants like glutathione (GSH), glutathione-S-transferase (GST), peroxidase (POX), superoxide dismutase (SOD), catalase (CAT) levels in testis were assessed. The data revealed a significant decrease in serum levels concentration of testosterone, LH and FSH levels in doxorubicin-injected rats. In addition, testis glutathione, glutathione transferase, peroxidase, SOD and CAT levels were decreased while lipid peroxidation concentration in the testis was increased as a result of doxorubicin injection. Co-administration of ethanolic purslane and seed extracts potentially improved the adverse changes in serum testosterone, luteinizing hormone (LH), follicle stimulating hormone (FSH) levels with an increase in testis antioxidants levels and reduction in lipid peroxidation. In conclusion, it can be suggested that dietary purslane extract supplementation may provide a cushion for a prolonged therapeutic option against DOX testicular toxicity without harmful side effects.

Keywords: doxorubicin, purslane, testis function, antioxidants

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Authors: Ashleigh Williams

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Micro- and nanoplastics’ (MNLPs) omnipresence and ecological accumulation is evident when surveying recent environmental impact studies. For example, in 2014 it was estimated that at least 52.3 trillion plastic microparticles are floating at sea, and scientists have even found plastics present remote Arctic ice and snow (5,6). Plastics have even found their way into precipitation, with more than 1000 tons of microplastic rain precipitating onto the Western United States in 2020. Even more recent studies evaluating the chemical safety of reusable plastic bottles found that hundreds of chemicals leached into the control liquid in the bottle (ddH2O, ph = 7) during a 24-hour time period. A consequence of the increased abundance in plastic waste in the air, land, and water every year is the bioaccumulation of MNLPs in ecosystems and trophic niches of the animal food chain, which could potentially cause increased direct and indirect exposure of humans to MNLPs via inhalation, ingestion, and dermal contact. Though the detrimental, toxic effects of MNLPs have been established in marine biota, much less is known about the potentially hazardous health effects of chronic MNLP ingestion in humans. Recent data indicate that long-term exposure to MNLPs could cause possible inflammatory and dysbiotic effects. However, toxicity seems to be largely dose-, as well as size-dependent. In addition, the transcytotic uptake of MNLPs through the intestinal epithelia in humans remain relatively unknown. To this point, the goal of the current study was to investigate the mechanisms of micro- and nanoplastic uptake and transcytosis of Polystyrene (PE) in human stem-cell derived, physiologically relevant in vitro intestinal model systems, and to compare the relative effect of particle size (30 nm, 100 nm, 500 nm and 1 µm), and concentration (0 µg/mL, 250 µg/mL, 500 µg/mL, 1000 µg/mL) on polystyrene MNLP uptake, transcytosis and intestinal epithelial model integrity. Observational and quantitative data obtained from confocal microscopy, immunostaining, transepithelial electrical resistance (TEER) measurements, cryosectioning, and ELISA cytokine assays of the proinflammatory cytokines Interleukin-6 and Interleukin-8 were used to evaluate the localization and transcytosis of polystyrene MNPs and its impact on epithelial integrity in human-derived intestinal in vitro model systems. The effect of Microfold (M) cell induction on polystyrene micro- and nanoparticle (MNP) uptake, transcytosis, and potential inflammation was also assessed and compared to samples grown under standard conditions. Microfold (M) cells, link the human intestinal system to the immune system and are the primary cells in the epithelium responsible for sampling and transporting foreign matter of interest from the lumen of the gut to underlying immune cells. Given the uptake capabilities of Microfold cells to interact both specifically and nonspecific to abiotic and biotic materials, it was expected that M- cell induced in vitro samples would have increased binding, localization, and potentially transcytosis of Polystyrene MNLPs across the epithelial barrier. Experimental results of this study would not only help in the evaluation of the plastic toxicity, but would allow for more detailed modeling of gut inflammation and the intestinal immune system.

Keywords: nanoplastics, enteroids, intestinal barrier, tissue engineering, microfold (M) cells

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Authors: M. Al Zallouha, Y. Landkocz, J. Brunet, R. Cousin, J. M. Halket, E. Genty, P. J. Martin, A. Verdin, D. Courcot, S. Siffert, P. Shirali, S. Billet

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Toluene is one of the most used Volatile Organic Compounds (VOCs) in the industry. Amongst VOCs, Benzene, Toluene, Ethylbenzene and Xylenes (BTEX) emitted into the atmosphere have a major and direct impact on human health. It is, therefore, necessary to minimize emissions directly at source. Catalytic oxidation is an industrial technique which provides remediation efficiency in the treatment of these organic compounds. However, during operation, the catalysts can release some compounds, called byproducts, more toxic than the original VOCs. The catalytic oxidation of a gas stream containing 1000ppm of toluene on Pd/α-Al2O3 can release a few ppm of benzene, according to the operating temperature of the catalyst. The development of new catalysts must, therefore, include chemical and toxicological validation phases. In this project, A549 human lung cells were exposed in air/liquid interface (Vitrocell®) to gas mixtures derived from the oxidation of toluene with a catalyst of Pd/α-Al2O3. Both exposure concentrations (i.e. 10 and 100% of catalytic emission) resulted in increased gene expression of Xenobiotics Metabolising Enzymes (XME) (CYP2E1 CYP2S1, CYP1A1, CYP1B1, EPHX1, and NQO1). Some of these XMEs are known to be induced by polycyclic organic compounds conventionally not searched during the development of catalysts for VOCs degradation. The increase in gene expression suggests the presence of undetected compounds whose toxicity must be assessed before the adoption of new catalyst. This enhances the relevance of toxicological validation of such systems before scaling-up and marketing.

Keywords: BTEX toxicity, air/liquid interface cell exposure, Vitrocell®, catalytic oxidation

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Authors: Pei-Ying Lo, Jing-Hao Ciou, Kai-Cheng Yang, Jia-Huei Zheng, Shih-Hsiang Huang, Kuen-Chan Lee, Er-Chieh Cho

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As-produced CNTs are insoluble in all organic solvents and aqueous solutions have imposed limitations to the use of CNTs. Therefore, how to debundle carbon nanotubes and to modify them for further uses is an important issue. There are several methods for the dispersion of CNTs in water using covalent attachment of hydrophilic groups to the surface of tubes. These methods, however, alter the electronic structure of the nanotubes by disrupting the network of sp2 hybridized carbons. In order to keep the nanotubes’ intrinsic mechanical and electrical properties intact, non-covalent interactions are increasingly being explored as an alternative route for dispersion. Apart from conventional surfactants such as sodium dodecylsulfate (SDS) or sodium dodecylbenzenesulfonate (SDBS) which are highly effective in dispersing CNTs, biopolymers have received much attention as dispersing agents due to the anticipated biocompatibility of the dispersed CNTs. Also, The pyrenyl group is known to interact strongly with the basal plane of graphene via π-stacking. In this study, a highly re-dispersible biopolymer is reported for the synthesis of pyrene-modified poly-L-lysine (PBPL) and poly(D-Glu, D-Lys) (PGLP). To provide the evidence of the safety of the PBPL/CNT & PGLP/CNT materials we use in this study, H1299 and HCT116 cells were incubated with PBPL/CNT & PGLP/CNT materials for toxicity analysis, MTS assays. The results from MTS assays indicated that no significant cellular toxicity was shown in H1299 and HCT116 cells. Furthermore, the fluorescence marker fluorescein isothiocyanate (FITC) was added to PBPL & PGLP dispersions. From the fluorescent measurements showed that the chemical functionalisation of the PBPL/CNT & PGLP/CNT conjugates with the fluorescence marker were successful. The fluorescent PBPL/CNT & PGLP/CNT conjugates could find application in medical imaging. In the next step, the GFP gene is immobilized onto PBPL/CNT conjugates by introducing electrostatic interaction. GFP-transfected cells that emitted fluorescence were imaged and counted under a fluorescence microscope. Due to the unique biocompatibility of PBPL modified CNTs, the GFP gene could be transported into H1299 cells without using antibodies. The applicability of such soluble and chemically functionalised polypeptide/CNT conjugates in biomedicine is currently investigated. We expect that this polypeptide/CNT system will be a safe and multi-functional nanomedical delivery platform and contribute to future medical therapy.

Keywords: carbon nanotube, nanotoxicology, GFP transfection, polypeptide/CNT hybrids

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Authors: Carlos E. Rodríguez-Rodríguez, Karla Ruiz-Hidalgo, Kattia Madrigal-Zúñiga, Juan Salvador Chin-Pampillo, Mario Masís-Mora, Elizabeth Carazo-Rojas

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One of the main causes of contamination linked to agricultural activities is the spillage and disposal of pesticides, especially during the loading, mixing or cleaning of agricultural spraying equipment. One improvement in the handling of pesticides is the use of biopurification systems (BPS), simple and cheap degradation devices where the pesticides are biologically degraded at accelerated rates. The biologically active core of BPS is the biomixture, which is constituted by soil pre-exposed to the target pesticide, a lignocellulosic substrate to promote the activity of ligninolitic fungi and a humic component (peat or compost), mixed at a volumetric proportion of 50:25:25. Considering the known ability of lignocellulosic fungi to degrade a wide range of organic pollutants, and the high amount of lignocellulosic waste used in biomixture preparation, the bioaugmentation of biomixtures with these fungi represents an interesting approach for improving biomixtures. The present work aimed at evaluating the effect of the bioaugmentation of rice husk based biomixtures with the fungus Trametes versicolor in the removal of the insectice/nematicide carbofuran (CFN) and to optimize the composition of the biomixture to obtain the best performance in terms of CFN removal and mineralization, reduction in formation of transformation products and decrease in residual toxicity of the matrix. The evaluation of several lignocellulosic residues (rice husk, wood chips, coconut fiber, sugarcane bagasse or newspaper print) revealed the best colonization by T. versicolor in rice husk. Pre-colonized rice husk was then used in the bioaugmentation of biomixtures also containing soil pre-exposed to CFN and either peat (GTS biomixture) or compost (GCS biomixture). After spiking with 10 mg/kg CBF, the efficiency of the biomixture was evaluated through a multi-component approach that included: monitoring of CBF removal and production of CBF transformation products, mineralization of radioisotopically labeled carbofuran (14C-CBF) and changes in the toxicity of the matrix after the treatment (Daphnia magna acute immobilization test). Estimated half-lives of CBF in the biomixtures were 3.4 d and 8.1 d in GTS and GCS, respectively. The transformation products 3-hydroxycarbofuran and 3-ketocarbofuran were detected at the moment of CFN application, however their concentration continuously disappeared. Mineralization of 14C-CFN was also faster in GTS than GCS. The toxicological evaluation showed a complete toxicity removal in the biomixtures after 48 d of treatment. The composition of the GCS biomixture was optimized using a central composite design and response surface methodology. The design variables were the volumetric content of fungally pre-colonized rice husk and the volumetric ratio compost/soil. According to the response models, maximization of CFN removal and mineralization rate, and minimization in the accumulation of transformation products were obtained with an optimized biomixture of composition 30:43:27 (pre-colonized rice husk:compost:soil), which differs from the 50:25:25 composition commonly employed in BPS. Results suggest that fungal bioaugmentation may enhance the performance of biomixtures in CFN removal. Optimization reveals the importance of assessing new biomixture formulations in order to maximize their performance.

Keywords: bioaugmentation, biopurification systems, degradation, fungi, pesticides, toxicity

Procedia PDF Downloads 286

Authors: Blessing A. Aderibigbe

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Combination therapy is a treatment approach that is used to prevent the emergence of drug resistance. This approach is used for the treatment of many chronic and infectious diseases. Potentiating agents are currently explored in combination therapy, resulting in excellent therapeutic outcomes. Breast cancer and malaria are two chronic conditions responsible globally for high death rates. In this research, a class of polymer-drug conjugates containing potentiating agents with either antimalarial or anticancer drugs were prepared by Michael Addition Polymerization reaction and ring-opening polymerization reaction. Conjugation of potentiating agents with bioactive compounds into the polymers resulted in conjugates with good water solubility, highly selective and non-toxic. In vitro cytotoxicity and in vitro antiplasmodial evaluation on the conjugates revealed that the conjugates were more effective when compared to the free drugs. The drug release studies further showed that the release profile of the drugs from the conjugates was sustained. The findings revealed the potential of polymer-drug conjugates to overcome drug toxicity and drug resistance, which is common with the currently used antimalarial and anticancer drugs.

Keywords: anticancer, antimalarials, combination therapy, polymer-drug conjugates

Procedia PDF Downloads 100

Authors: V. Ivanov, J. Chu, V. Stabnikov

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Different biotechnological methods for the production of construction materials and for the performance of construction processes in situ are developing within a new scientific discipline of Construction Biotechnology. The aim of this research was to develop and test new biotechnologies and biotechnological grouts for the minimization of the hydraulic conductivity of the fractured rocks and porous soil. This problem is essential to minimize flow rate of groundwater into the construction sites, the tunneling space before and after excavation, inside levies, as well as to stop water seepage from the aquaculture ponds, agricultural channels, radioactive waste or toxic chemicals storage sites, from the landfills or from the soil-polluted sites. The conventional fine or ultrafine cement grouts or chemical grouts have such restrictions as high cost, viscosity, sometime toxicity but the biogrouts, which are based on microbial or enzymatic activities and some not expensive inorganic reagents, could be more suitable in many cases because of lower cost and low or zero toxicity. Due to these advantages, development of biotechnologies for biogrouting is going exponentially. However, most popular at present biogrout, which is based on activity of urease- producing bacteria initiating crystallization of calcium carbonate from calcium salt has such disadvantages as production of toxic ammonium/ammonia and development of high pH. Therefore, the aim of our studies was development and testing of new biogrouts that are environmentally friendly and have low cost suitable for large scale geotechnical, construction, and environmental applications. New microbial biotechnologies have been studied and tested in the sand columns, fissured rock samples, in 1 m3 tank with sand, and in the pack of stone sheets that were the models of the porous soil and fractured rocks. Several biotechnological methods showed positive results: 1) biogrouting using sequential desaturation of sand by injection of denitrifying bacteria and medium following with biocementation using urease-producing bacteria, urea and calcium salt decreased hydraulic conductivity of sand to 2×10-7 ms-1 after 17 days of treatment and consumed almost three times less reagents than conventional calcium-and urea-based biogrouting; 2) biogrouting using slime-producing bacteria decreased hydraulic conductivity of sand to 1x10-6 ms-1 after 15 days of treatment; 3) biogrouting of the rocks with the width of the fissures 65×10-6 m using calcium bicarbonate solution, that was produced from CaCO3 and CO2 under 30 bars pressure, decreased hydraulic conductivity of the fissured rocks to 2×10-7 ms-1 after 5 days of treatment. These bioclogging technologies could have a lot of advantages over conventional construction materials and processes and can be used in geotechnical engineering, agriculture and aquaculture, and for the environmental protection.

Keywords: biocementation, bioclogging, biogrouting, fractured rocks, porous soil, tunneling space

Procedia PDF Downloads 184

Authors: Azimeh Rajaee, Lingyun Zhao, Shi Wang, Yaqiang Liu

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In recent years many studies have been focused on bismuth-based nanoparticles as radiosensitizer and contrast agent in radiation therapy and imaging due to the high atomic number (Z = 82), high photoelectric absorption, low cost, and low toxicity. This study aims to introduce a new multifunctional bismuth-based nanoparticle as a theranostic agent for radiotherapy, computed tomography (CT) and magnetic resonance imaging (MRI). We synthesized bismuth ferrite (BFO, BiFeO3) nanoparticles by sol-gel method and surface of the nanoparticles were modified by Polyethylene glycol (PEG). After proved biocompatibility of the nanoparticles, the ability of them as contract agent in Computed tomography (CT) and magnetic resonance imaging (MRI) was investigated. The relaxation time rate (R2) in MRI and Hounsfield unit (HU) in CT imaging were increased with the concentration of the nanoparticles. Moreover, the effect of nanoparticles on dose enhancement in low energy was investigated by clonogenic assay. According to clonogenic assay, sensitizer enhancement ratios (SERs) were obtained as 1.35 and 1.76 for nanoparticle concentrations of 0.05 mg/ml and 0.1 mg/ml, respectively. In conclusion, our experimental results demonstrate that the multifunctional nanoparticles have the ability to employ as multimodal imaging and therapy to enhance theranostic efficacy.

Keywords: molecular imaging, nanomedicine, radiotherapy, theranostics

Procedia PDF Downloads 280

Authors: Hamid Abdulroof Saleh

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Background: Dioxins are one of the most widely distributed environmental pollutants. Dioxins consist of feedstock during the preparation of some industries, such as the paper industry as they can be produced in the atmosphere during the process of burning garbage and waste, especially medical waste. Dioxins can be found in the adipose tissues of animals in the food chain as well as in human breast milk. 2,3,7,8-Tetrachlorodibenzo-pdioxin (TCDD) is the most toxic component of a large group of dioxins. Humans are exposed to TCDD through contaminated food items like meat, fish, milk products, eggs etc. Recently, natural formulations relating to reducing or eliminating TCDD toxicity have been in focus. Ginger rhizome (Zingiber officinale R., family: Zingiberaceae), is used worldwide as a spice. Both antioxidative and androgenic activity of Z. officinale was reported in animal models. Researchers showed that ginger oil has dominative protective effect on DNA damage and might act as a scavenger of oxygen radical and might be used as an antioxidant. Aim of the work: The present study was undertaken to evaluate the toxic effect of TCDD on the structure and histoarchitecture of the testis and the protective role of co-administration of ginger root extract to prevent this toxicity. Materials & Methods: Male adult rats of Sprague-Dawley strain were assigned to four groups, eight rats in each; control group, dioxin treated group (given TCDD at the dose of 100 ng/kg Bwt/day by gavage), ginger treated group (given 50 mg/kg Bwt/day of ginger root extract by gavage), dioxin and ginger treated group (given TCDD at the dose of 100 ng/kg Bwt/day and 50 mg/kg Bwt/day of ginger root extract by gavages). After three weeks, rats were weighed and sacrificed where testis were removed and weighted. The testes were processed for routine paraffin embedding and staining. Tissue sections were examined for different morphometric and histopathological changes. Results: Dioxin administration showed a harmful effects in the body, testis weight and other morphometric parameters of the testis. In addition, it produced varying degrees of damage to the seminiferous tubules, which were shrunken and devoid of mature spermatids. The basement membrane was disorganized with vacuolization and loss of germinal cells. The co-administration of ginger root extract showed obvious improvement in the above changes and showed reversible morphometric and histopathological changes of the seminiferous tubules. Conclusion: Ginger root extract treatment in this study was successful in reversing all morphometric and histological changes of dioxin testicular damage. Therefore, it showed a protective effect on testis against dioxin toxicity.

Keywords: dioxin, ginger, rat, testis

Procedia PDF Downloads 397

Authors: Aarti Sharma, Sarita Kumar, Pushplata Tripathi

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Aedes aegypti L. is one of the most important insect vectors in the world transmitting several diseases of concern; dengue fever, dengue haemorrhagic fever and yellow fever. Though since ages the control of dengue vector is primarily relied upon the use of synthetic chemical insecticides, the continued and indiscriminate use of insecticides for their control has received wide public apprehension because of multifarious problems including insecticide resistance, resurgence of pest species, environmental pollution, toxic hazards to humans and non-target organisms. These problems have necessitated the need to explore and develop alternative strategies using eco-friendly and bio-degradable plant products. Bio-insecticides, despite being the focus of research nowadays, have not been investigated much regarding their physiological effects on the mosquitoes. Thus, the present studies were carried out to investigate the anti-mosquito potential of the leaf and stem hexane extracts of Achyranthes aspera against early fourth instars of Aedes aegypti L and their effects on the histological architecture of their midgut. The larvicidal bioassays conducted with the A. aspera leaf hexane extracts revealed the respective LC30, LC50 and LC90 values of 66.545 ppm, 82.555 ppm, 139.817 ppm while the assays with stem hexane extracts resulted in respective values of 54.982 ppm, 68.133 ppm, 115.075 ppm. The studies clearly indicate the efficacy of extracts as larvicidal agents against Ae. aegypti, the stem extracts being found more effective than the leaf extracts. When the larvae assayed with extracts were investigated for the modifications in the histo-architecture of the midgut, the studies showed significant damage, shrinkage, distortion and vacuolization of gut tissues and peritrophic membrane causing disintegration of epithelial cells and cytoplasmic organelles; extent of toxicity and damage varied depending upon the concentration and exposure time period. These changes revealed appreciable stomach poison potential of A. aspera extracts against Ae. aegypti larvae, which may have also caused adverse impact on the growth and development of larvae. These effects were also found to be more pronounced with the stem extract than the leaf extract. Our findings may prove significant suggesting the use of A. aspera extract as a bio-insecticide against early fourth instar larvae of Ae. aegypti. Further studies are needed to identify the bioactive component in the extracts and to ascertain the use of component in the fields as anti-mosquito control agent.

Keywords: Achyranthes aspera, Aedes aegypti, histological architecture, larvicidal, midgut, stomach poison

Procedia PDF Downloads 265

Authors: Tella Toluwani, Adegbegi Ademuyiwa, Musei Chiedu, Adekunle Odola, Ayangbenro Ayansina, Adaramoye Oluwatosin

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Dithiocarbamates are very useful biological agents with antioxidant properties. Diclofenac (DIC) is a non-steroidal analgesic, anti-inflammatory, and antipyretic agent. The use of diclofenac has been linked with reproductive toxicity/damage. The purpose of this study is (i) To investigate the therapeutic potential of diisopropyldithiocarbamate sodium salt (Na(i-Pr₂dtc)) and vitamin E (VIT E) against diclofenac induced toxicity in the testes of male Wistar rats. (ii) To investigate the effect of (Na(i-Pr₂dtc)) and vitamin E on ameliorating damage done to the testes through histological analysis of the testes. Thirty-six (36) male Wistar rats were used for the experiment, they were divided into six (6) groups, the animals in group 1 served as control, animals in groups 2, 3, 4, 5 and 6 received DIC only, DIC and (Na(i-Pr₂dtc)), DIC and VIT E, (Na(i-Pr₂dtc) only and VIT E only respectively. A single dose of 100 mg/kg body weight of DIC was administered to male Wistar rats, while 30 mg/kg body weight of (Na(i-Pr₂dtc)) was used to treat both normal and DIC treated animals, control animals were treated with the vehicle, after 24 hrs of treatment the animals were euthanized and the testes were removed for analysis. The treatment of rats with Na(i-Pr₂dtc) significantly restored catalase (CAT) activity depressed by diclofenac. (Na(i-Pr₂dtc)) also restored glutathione levels reduced by DIC treatment and this was also accompanied by reduced lipid peroxidation (LPO) level. VIT E significantly restored superoxide dismutase (SOD) activity when compared with DIC only treated animals. Photomicrographs of testes from (Na(i-Pr₂dtc)) treated rats showed seminiferous epithelium with no lesions. We conclude that (Na(i-Pr₂dtc)) has an antioxidant effect, which might be related to the dose and duration of administration.

Keywords: diisopropyldithiocarbamate sodium salt, diclofenac, vitamin E, testes

Procedia PDF Downloads 162

Authors: A. Goma Amira, U. E. Mahrous

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Measuring the effect of perinatal lead exposure on learning ability of offspring is considered as a sensitive and selective index for providing an early marker for central nervous system damage produced by this toxic metal. A total of 35 Sprague-Dawley adult rats were used to investigate the effect of lead acetate toxicity on behavioral patterns of adult female rats and learning ability of offspring. Rats were allotted into 4 groups, group one received 1g/l lead acetate (n=10), group two received 1.5g/l lead acetate (n=10), group three received 2g/l lead acetate in drinking water (n=10), and control group did not receive lead acetate (n=5) from 8th day of pregnancy till weaning of pups. The obtained results revealed a dose-dependent increase in the feeding time, drinking frequency, licking frequency, scratching frequency, licking litters, nest building, and retrieving frequencies, while standing time increased significantly in rats treated with 1.5g/l lead acetate than other treated groups and control. On the contrary, lying time decreased gradually in a dose-dependent manner. Moreover, movement activities were higher in rats treated with 1g/l lead acetate than other treated groups and control. Furthermore, time spent in closed arms was significantly lower in rats given 2g/l lead acetate than other treated groups, while they spent significantly much time spent in open arms than other treated groups which could be attributed to occurrence of adaptation. Furthermore, number of entries in open arms was-dose dependent. However, the ratio between open/closed arms revealed a significant decrease in rats treated with 2g/l lead acetate than the control group.

Keywords: lead toxicity, rats, learning ability, behavior

Procedia PDF Downloads 348

Authors: M. Helen

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Chemical graph serves as a convenient model for any real or abstract chemical system. Dendrimers are novel three dimensional hyper branched globular nanopolymeric architectures. Drug delivery scientists are especially enthusiastic about possible utility of dendrimers as drug delivery tool. Dendrimers like poly L lysine (PLL), poly-propylene imine (PPI) and poly-amidoamine (PAMAM), etc., are used as gene carrier in drug delivery system because of their chemical characteristics. These characteristics of chemical compounds are analysed using topological indices (invariants under graph isomorphism) such as Wiener index, Zagreb index, etc., Prof. V. R. Kulli motivated by the application of Zagreb indices in finding the total π energy and derived Gourava indices which is an improved version over Zagreb indices. In this paper, we study the structure of PLL-Dendrimer that has the following applications: reduction in toxicity, colon delivery, and topical delivery. Also, we determine first and second Gourava indices, first and second hyper Gourava indices, product and sum connectivity Gourava indices for PLL-Dendrimer. Gourava Indices have found applications in Quantitative Structure-Property Relationship (QSPR)/ Quantitative Structure-Activity Relationship (QSAR) studies.

Keywords: connectivity Gourava indices, dendrimer, Gourava indices, hyper GouravaG indices

Procedia PDF Downloads 100

Authors: Aberdam Edith, Sangari Linda, Petit Isabelle, Aberdam Daniel

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Background and Rationale: Transparent avascularised cornea is essential for normal vision and depends on limbal stem cells (LSC) that reside between the cornea and the conjunctiva. Ocular burns or injuries may destroy the limbus, causing limbal stem cell deficiency (LSCD). The cornea becomes vascularised by invaded conjunctival cells, the stroma is scarring, resulting in corneal opacity and loss of vision. Grafted autologous limbus or cultivated autologous LCS can restore the vision, unless the two eyes are affected. Alternative cellular sources have been tested in the last decades, including oral mucosa or hair follicle epithelial cells. However, only partial success has been achieved by the use of these cells since they were not able to uniformly commit into corneal epithelial cells. Human pluripotent stem cells (iPSC) display both unlimited growth capacity and ability to differentiate into any cell type. Our goal was to design a standardized and reproducible protocol to produce transplantable autologous LSC from patients through cell reprogramming technology. Methodology: First, keratinocyte primary culture was established from a small number of plucked hair follicles of healthy donors. The resulting epithelial cells were reprogrammed into induced pluripotent stem cells (iPSCs) and further differentiate into corneal epithelial cells (CEC), according to a robust protocol that recapitulates the main step of corneal embryonic development. qRT-PCR analysis and immunofluorescent staining during the course of differentiation confirm the expression of stage specific markers of corneal embryonic lineage. First appear ectodermal progenitor-specific cytokeratins K8/K18, followed at day 7 by limbal-specific PAX6, TP63 and cytokeratins K5/K14. At day 15, K3/K12+-corneal cells are present. To amplify the iPSC-derived LSC (named COiPSC), intact small epithelial colonies were detached and cultivated in limbal cell-specific medium. In that culture conditions, the COiPSC can be frozen and thaw at any passage, while retaining their corneal characteristics for at least eight passages. To evaluate the potential of COiPSC as an alternative ocular toxicity model, COiPSC were treated at passage P0 to P4 with increasing amounts of SDS and Benzalkonium. Cell proliferation and apoptosis of treated cells was compared to LSC and the SV40-immortalized human corneal epithelial cell line (HCE) routinely used by cosmetological industrials. Of note, HCE are more resistant to toxicity than LSC. At P0, COiPSC were systematically more resistant to chemical toxicity than LSC and even to HCE. Remarkably, this behavior changed with passage since COiPSC at P2 became identical to LSC and thus closer to physiology than HCE. Comparative transcriptome analysis confirmed that COiPSC from P2 are similar to a mixture of LSC and CEC. Finally, by organotypic reconstitution assay, we demonstrated the ability of COiPSC to produce a 3D corneal epithelium on a stromal equivalent made of keratocytes. Conclusion: COiPSC could become valuable for two main applications: (1) an alternative robust tool to perform, in a reproducible and physiological manner, toxicity assays for cosmetic products and pharmacological tests of drugs. (2). COiPSC could become an alternative autologous source for cornea transplantation for LSCD.

Keywords: Limbal stem cell deficiency, iPSC, cornea, limbal stem cells

Procedia PDF Downloads 380

Authors: Gloria A. Adewumi, Andrew C. Eloka-Eboka, Freddie L. Inambao

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Bio-based carbon nanotubes (CNTs) have received considerable research attention due to their comparative advantages of high level stability, simplistic use, low toxicity and overall environmental friendliness. New potentials for improvement in heat transfer applications are presented due to their high aspect ratio, high thermal conductivity and special surface area. Phonons have been identified as being responsible for thermal conductivities in carbon nanotubes. Therefore, understanding the mechanism of heat conduction in CNTs involves investigating the difference between the varieties of phonon modes and knowing the kinds of phonon modes that play the dominant role. In this review, a reference to a different number of studies is made and in addition, the role of phonon relaxation rate mainly controlled by boundary scattering and three-phonon Umklapp scattering process was investigated. Results show that the phonon modes are sensitive to a number of nanotube conditions such as: diameter, length, temperature, defects and axial strain. At a low temperature (<100K) the thermal conductivity increases with increasing temperature. A small nanotube size causes phonon quantization which is evident in the thermal conductivity at low temperatures.

Keywords: carbon nanotubes, phonons, thermal conductivity, Umklapp process

Procedia PDF Downloads 327

Authors: Elena Maria Scalisi

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Currently, photodegradation by nanoparticles (NPs) is a common solution for wastewater treatment. Nanoparticles are efficient for removing organic and inorganic pollutants, heavy metals from wastewater and killing microorganisms through environmentally friendly. In this context, the major representative of photocatalytic technology for industrial wastewater treatment are TiO₂ nanoparticles (TiO₂-NPs). TiO₂-NPs have a strong catalytic activity that depends to their physicochemical properties. Thanks to their small size (between 1-100 nm), nanoparticles occupy less volume, then their surface area increases. The increase in the surface-to-volume ratio results in the increase of the particle surface energy, which improve their reactivity potential. However, these unique properties represent risks to the ecosystems and organisms when unintentionally TiO₂-NPs are release into the environment and absorbed by living organisms. Several studies confirm that there is a high level of interest concerning the safety of TiO₂-NPs in the aquatic environment, furthermore, ecotoxicological tools are useful to correctly evaluate their toxicity. In the current study, we aimed to characterize potential toxic effects of TiO₂-NP suspension to zebrafish during embryo-larval stages to evaluate parameters such as survival rates, malformation, hatching, the overall length of the larvae heartbeat, and biochemical biomarkers that reflect the acute toxicity and sublethal effects of TiO₂-NPs. Zebrafish embryos were exposed to titanium dioxide nanoparticles (TiO₂-NPs at 1mg/L, 2mg/L, and 4mg/L) from fertilization to the free swimming stage (144hpf). Every day, we recorded the toxicological endpoints, moreover, immunohistochemical analysis has been performed at the end of the exposure. In particular, we have evaluate the expression of the following biomarkers: Heat Shock Protein 70 (HSP70), Poly ADP-Ribose Polymerase-1 (PARP-1), Metallothioneins (MTs). Our results have shown that hatch ability, survival, and malformation rate were not affected by TiO₂ NPs at these exposure levels. However, TiO₂-NPs caused an increase of heartbeat and reduction of body length; at the same time, TiO₂-NPs have inducted the production of ROS and the expression of oxidative stress biomarkers HSP70 and PARP-1. Hight positivity for PARP-1 at all concentration tested was observed. As regards MT, positivity was found in the expression of this biomarker in the whole body of the embryo, with the exception of the end of the tail. Metallothioneins (MT) are biomarkers widely used in environmental monitoring programs for aquatic creatures. At the light of our results i.e. no death until the end of the experiment (144hpf), no malformation and expression of the biomarkers mentioned, it is evident that zebrafish larvae with their natural detoxification pathways are able to resist the presence of toxic substances and then they can tolerate the presence of metal concentrations. However, an excessive oxidative state can compromise cell function, therefore the uncontrolled release of nanoparticles into the environment is severe and must be constantly monitored.

Keywords: nanoparticles, embryo zebrafish, HSP70, PARP-1

Procedia PDF Downloads 111

Authors: Bea Carmel H. Casiding, Charmaine A. Guy, Funny Jovis P. Malasan, Katrina Chelsea B. Manlutac, Danielle Ann N. Novilla, Marianne R. Oliveros, Magnolia C. Sibulo

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Moon jellyfish, Aurelia aurita, has become a popular research organism for diverse studies. Recent studies have verified the prevention of blood clotting properties of the moon jellyfish tentacle extract through in vitro methods. The purpose of this study was to validate the blood clotting ability of A. aurita tentacle extract using in vivo method of experimentation. The tentacles of A. aurita jellyfish were excised and filtered then centrifuged at 3000xg for 10 minutes. The crude nematocyst extract was suspended in 1:6 ratios with phosphate buffer solution and sonicated for three periods of 20 seconds each at 50 Hz. Protein concentration of the extract was determined using Bradford Assay. Bovine serum albumin was the standard solution used with the following concentrations: 35.0, 70.0, 105.0, 140.0, 175.0, 210.0, 245.0, and 280.0 µg/mL. The absorbance was read at 595 nm. Toxicity testing from OECD guidelines was adapted. The extract suspended in phosphate-buffered saline solution was arbitrarily set into three doses (0.1mg/kg, 0.3mg/kg, 0.5mg/kg) and were administered daily for five days to the experimental groups of five male Sprague-Dawley rats (one dose per group). Before and after the administration period, bleeding time and clotting time tests were performed. The One-way Analysis of Variance (ANOVA) was used to analyze the difference of before and after bleeding time and clotting time from the three treatment groups, time, positive and negative control groups. The average protein concentration of the sonicated crude tentacle extract was 206.5 µg/mL. The highest dose administered (0.5mg/kg) produced significant increase in the time for both bleeding and clotting tests. However, the preceding lower dose (0.3mg/kg) only was significantly effective for clotting time test. The protein contained in the tentacle extract with a concentration of 206.5 mcg/mL and dose of 0.3 mg/kg and 0.5 mg/kg of A. aurita elicited anticoagulating activity.

Keywords: anticoagulant, bleeding time test, clotting time test, moon jellyfish

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Authors: Guadalupe Pérez, Jorge Islas, Mirna Guevara, Raúl Suárez

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Jatropha curcas is a perennial oleaginous plant that is currently considered an energy crop with high potential as an environmentally sustainable biofuel. During the last decades, research in biofuels has grown in tropical and subtropical regions in Latin America. However, as far we know, there are no reports on the growth and yield patterns of Jatropha curcas under the specific agro climatic scenarios of the State of Morelos, Mexico. This study presents the results of 52 months monitoring of 10 toxic and non-toxic ecotypes of Jatropha curcas (E1M, E2M, E3M, E4M, E5M, E6O, E7O, E8O, E9C, E10C) in an experimental plantation with minimum watering and fertilization resources. The main objective is to identify the ecotypes with the highest potential as biodiesel raw material in the select region, by developing experimental information. Specifically, we monitored biophysical and growth parameters, including plant survival and seed production (at the end of month 52), to study the performance of each ecotype and to establish differences among the variables of morphological growth, net seed oil content, and toxicity. To analyze the morphological growth, a statistical approach to the biophysical parameters was used; the net seed oil content -80 to 192 kg/ha- was estimated with the first harvest; and the toxicity was evaluated by examining the phorbol ester concentration (µg/L) in the oil extracted from the seeds. The comparison and selection of ecotypes was performed through a methodology developed based on the normalization of results. We identified four outstanding ecotypes (E1M, E2M, E3M, and E4M) that can be used to establish Jatropha curcas as energy crops in the state of Morelos for feasible agro-industrial production of biodiesel and other products related to the use of biomass.

Keywords: biodiesel production, Jatropha curcas, seed oil content, toxic and non-toxic ecotypes

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Authors: Mohamed A. Morsy, Azza A. El-Sheikh, Abdulla Y. Al-Taher

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Resveratrol (RES) is a well-known polyphenol antioxidant. We have previously shown that testicular protective effect of RES against the anticancer drug methotrexate (MTX)-induced toxicity involves transporter-mediated mechanisms. Here, we investigated the effect of RES on MTX-induced nephrotoxicity. Rats were administered RES (10 mg/kg/day) for 8 days, with or without a single MTX dose (20 mg/kg i.p.) at day 4 of the experiment. MTX induced nephrotoxicity evident by significantly increase in serum blood urea nitrogen and creatinine compared to control, as well as distortion of kidney microscopic structure. MTX also significantly increased renal nitric oxide level, with induction of inducible nitric oxide synthase expression. MTX also significantly up-regulated fas ligand and caspase 3. Administering RES prior to MTX significantly improved kidney function and microscopic picture, as well as significantly decreased nitrosative and apoptotic markers compared to MTX alone. RES, but not MTX, caused significant increase in expression of breast cancer resistance protein (BCRP), an apical efflux renal transporter that participates in urinary elimination of both MTX and RES. Interestingly, concomitant MTX and RES caused further up-regulation of renal Bcrp compared to RES alone. Using Human BCRP ATPase assay, both RES and MTX exhibited dose-dependent increase in ATPase activity, with Km values of 0.52 ± 0.03 and 30.9 ± 4.2 µM, respectively. Furthermore, combined RES and MTX caused ATPase activity which was significantly less than maximum ATPase activity attained by the positive control; sulfasalazine (12.5 µM). In conclusion, RES exerted nephro-protection against MTX-induced toxicity through anti-nitrosative and anti-apoptotic effects, as well as via up-regulation of renal Bcrp.

Keywords: methotrexate, resveratrol, nephrotoxicity, breast cancer resistance protein

Procedia PDF Downloads 262