Search results for: toxicity
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 924

Search results for: toxicity

654 Protective Efficacy of Moringa oleifera against Oxidative Ovarian Damage and Reproductive Failure in Female Rats Caused by Cyclophosphamide

Authors: Seham Samir Soliman, Ahmed A.Suliman, Khaled Fathy, Ahmed A. Sedik

Abstract:

Cyclophosphamide (CP), an antineoplastic drug, has been found to induce reproductive damage. It is essential to develop approaches aimed at safeguarding ovarian tissue integrity in women experiencing reproductive toxicity as a result of chemotherapy. The current study was conducted to assess the impact of an extract derived from Moringa oleifera (M. oleifera) leaves on ovarian damage produced by CP. A total of 32 female Wistar Albino rats, which were in a healthy cycling state, were randomly separated into 4 groups, with every group contains 8 rats. The first group was administered intraperitoneal (i.p.) saline. The second group was administered a solitary intraperitoneal dosage of cyclophosphamide (200 mg/kg). The third one received M. oleifera extract (150 mg/kg orally) for 20 days, followed by i.p. of CP on the last day of the experiment. The fourth group received M. oleifera extract (250 mg/kg orally) for 20 days, followed by i.p. of CP on the last day of the experiment. Hormonal assessments, including luteinizing hormone (LH), estrogen (ES), and follicle-stimulating hormone (FSH), were performed 24 hours after CP administration. In addition, evaluating the antioxidant status and inflammatory response against CP. Moreover, conducting detailed histopathological and ultra-structural pictures of the ovary. Our findings reported that rats intoxicated with CP exhibited elevated levels of FSH, LH, malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α), and a decrease in E₂, and glutathione (GSH) levels. Pre-treatment with M. oleifera extract (250 mg/kg orally) ameliorated the disturbance in hormonal changes, oxidative stress indices, and the levels of pro-inflammatory mediators. Also, the histopathological and ultra-structural pictures of the ovaries were improved significantly in rats. In conclusion, M. oleifera extract possesses a significant protective role against CP-induced acute reproductive toxicity via modulating the values of FSH, LH, E₂ and quenching the release of reactive oxygen species and inflammatory mediators in female rats.

Keywords: cyclophosphamide, Moringa oleifera, ovarian function, oxidative stress, pro-inflammatory mediators

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653 Lead-Free Inorganic Cesium Tin-Germanium Triiodide Perovskites for Photovoltaic Application

Authors: Seyedeh Mozhgan Seyed-Talebi, Javad Beheshtian

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The toxicity of lead associated with the lifecycle of perovskite solar cells (PSCs( is a serious concern which may prove to be a major hurdle in the path toward their commercialization. The current proposed lead-free PSCs including Ag(I), Bi(III), Sb(III), Ti(IV), Ge(II), and Sn(II) low-toxicity cations are still plagued with the critical issues of poor stability and low efficiency. This is mainly because of their chemical stability. In the present research, utilization of all inorganic CsSnGeI3 based materials offers the advantages to enhance resistance of device to degradation, reduce the cost of cells, and minimize the carrier recombination. The presence of inorganic halide perovskite improves the photovoltaic parameters of PCSs via improved surface coverage and stability. The inverted structure of simulated devices using a 1D simulator like solar cell capacitance simulator (SCAPS) version 3308 involves TCOHTL/Perovskite/ETL/Au contact layer. PEDOT:PSS, PCBM, and CsSnGeI3 used as hole transporting layer (HTL), electron transporting layer (ETL), and perovskite absorber layer in the inverted structure for the first time. The holes are injected from highly stable and air tolerant Sn0.5Ge0.5I3 perovskite composition to HTM and electrons from the perovskite to ETL. Simulation results revealed a great dependence of power conversion efficiency (PCE) on the thickness and defect density of perovskite layer. Here the effect of an increase in operating temperature from 300 K to 400 K on the performance of CsSnGeI3 based perovskite devices is investigated. Comparison between simulated CsSnGeI3 based PCSs and similar real testified devices with spiro-OMeTAD as HTL showed that the extraction of carriers at the interfaces of perovskite absorber depends on the energy level mismatches between perovskite and HTL/ETL. We believe that optimization results reported here represent a critical avenue for fabricating the stable, low-cost, efficient, and eco-friendly all-inorganic Cs-Sn-Ge based lead-free perovskite devices.

Keywords: hole transporting layer, lead-free, perovskite solar cell, SCAPS-1D, Sn-Ge based

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652 Top-Down Approach for Fabricating Hematite Nanowire Arrays

Authors: Seungmin Shin, Jin-Baek Kim

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Hematite (α-Fe2O3) has very good semiconducting properties with a band gap of 2.1 eV and is antiferromagnetic. Due to its electrochemical stability, low toxicity, wide abundance, and low-cost, hematite, it is a particularly attractive material for photoelectrochemical cells. Additionally, hematite has also found applications in gas sensing, field emission, heterogeneous catalysis, and lithium-ion battery electrodes. Here, we discovered a new universal top-down method for the synthesis of one-dimensional hematite nanowire arrays. Various shapes and lengths of hematite nanowire have been easily fabricated over large areas by sequential processes. The obtained hematite nanowire arrays are promising candidates as photoanodes in photoelectrochemical solar cells.

Keywords: hematite, lithography, nanowire, top-down process

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651 An Investigation of Peptide Functionalized Gold Nanoparticles On Colon Cancer Cells For Biomedical Application

Authors: Rolivhuwa Bishop Ramagoma1*, Lynn Cairncross1, , Saartjie Roux1

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According to the world health organisation, colon cancer is among the most common cancers diagnosed in both men and women. Specifically, it is the second leading cause of cancer related deaths accounting for over 860 000 deaths worldwide in 2018. Currently, chemotherapy has become an essential component of most cancer treatments. Despite progress in cancer drug development over the previous years, traditional chemotherapeutic drugs still have low selectivity for targeting tumour tissues and are frequently constrained by dose-limiting toxicity. The creation of nanoscale delivery vehicles capable of directly directing treatment into cancer cells has recently caught the interest of researchers. Herein, the development of peptide-functionalized polyethylene glycol gold nanoparticles (Peptide-PEG-AuNPs) as a cellular probe and delivery agent is described, with the higher aim to develop a specific diagnostic prototype and assess their specificity not only against cell lines but primary human cells as well. Gold nanoparticles (AuNPs) were synthesized and stabilized through chemical conjugation. The synthesized AuNPs were characterized, stability in physiological solutions was assessed, their cytotoxicity against colon carcinoma and non-carcinoma skin fibroblasts was also studied. Furthermore, genetic effect through real-time polymerase chain reaction (RT-PCR), localization and uptake, peptide specificity were also determined. In this study, different peptide-AuNPs were found to have preferential toxicity at higher concentrations, as revealed by cell viability assays, however, all AuNPs presented immaculate stability for over 3 months following the method of synthesis. The final obtained peptide-PEG-AuNP conjugates showed good biocompatibility in the presence of high ionic solutions and biological media and good cellular uptake. Formulation of colon cancer specific targeting peptide was successful, additionally, the genes/pathways affected by the treatments were determined through RT-PCR. Primary cells study is still on going with promising results thus far.

Keywords: nanotechnology, cancer, diagnosis, therapeutics, gold nanoparticles.

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650 Assessment of Acute Oral Toxicity Studies and Anti Diabetic Activity of Herbal Mediated Nanomedicine

Authors: Shanker Kalakotla, Krishna Mohan Gottumukkala

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Diabetes is a metabolic disorder characterized by hyperglycemia, carbohydrates, altered lipids and proteins metabolism. In recent research nanotechnology is a blazing field for the researchers; latterly there has been prodigious excitement in the nanomedicine and nano pharmacological area for the study of silver nanoparticles synthesis using natural products. Biological methods have been used to synthesize silver nanoparticles in presence of medicinally active antidiabetic plants, and this intention made us assess the biologically synthesized silver nanoparticles from the seed extract of Psoralea corylfolia using 1 mM silver nitrate solution. The synthesized herbal mediated silver nanoparticles (HMSNP’s) then subjected to various characterization techniques such as XRD, SEM, EDX, TEM, DLS, UV and FT-IR respectively. In current study, the silver nanoparticles tested for in-vitro anti-diabetic activity and possible toxic effects in healthy female albino mice by following OECD guidelines-425. Herbal mediated silver nanoparticles were successfully obtained from bioreduction of silver nitrate using Psoralea corylifolia plant extract. Silver nanoparticles have been appropriately characterized and confirmed using different types of equipment viz., UV-vis spectroscopy, XRD, FTIR, DLS, SEM and EDX analysis. From the behavioral observations of the study, the female albino mice did not show sedation, respiratory arrest, and convulsions. Test compounds did not cause any mortality at the dose level tested (i.e., 2000 mg/kg body weight) doses till the end of 14 days of observation and were considered safe. It may be concluded that LD50 of the HMSNPs was 2000mg/kg body weight. Since LD50 of the HMSNPs was 2000mg/kg body weight, so the preferred dose range for HMSNPs falls between the levels of 200 and 400 mg/kg. Further In-vivo pharmacological models and biochemical investigations will clearly elucidate the mechanism of action and will be helpful in projecting the currently synthesized silver nanoparticles as a therapeutic target in treating chronic ailments.

Keywords: herbal mediated silver nanoparticles, HMSNPs, toxicity of silver nanoparticles, PTP1B in-vitro anti-diabetic assay female albino mice, 425 OECD guidelines

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649 Anti-Hypertensive Effect of Proteolysate Generated from Actinopyga lecanora in Rats

Authors: Mahdokht Sadeghvishkaei, Azizah Abdul-Hamid, Amin Ismail, Nazamid Saari

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Hypertension is a common and serious chronic health problem and known as the most important risk factor for development of many diseases such as stroke. Since angiotensin I-converting enzyme (ACE) is the key enzyme involved in blood pressure, one of the well accepted mechanisms to control hypertension is through ACE inhibition. The ACE inhibitory effect of Actinopyga lecanora (stone fish) proteolysate in vitro had been reported. Hence, this study aimed to evaluate the ACE inhibitory potential of Actinopyga lecanora proteolysate in vivo in normotensive rats. Therefore the ACE inhibitory capability of the proteolysate to prevent increasing systolic blood pressure, after inducing hypertension by angiotensin I was examined. The pre-fed rats with the proteolysates at various doses (200, 400, 800 mg/kg body weight) revealed the significant (p ≤ 0.05) suppression effect compared with control groups. Furthermore, different doses of the proteolysate (200, 400, 800 mg/kg body weight) were examined to find its optimum effective dose. Results depicted that 800 mg proteolysate/kg body weight significantly reduced systolic blood pressure without negative effect on normal blood pressure (p ≤ 0.05). Furthermore, Sub-acute toxicity study based on OECD guideline demonstrated the safety of the proteolysate in vivo. The present study indicated that the proteolysate at a dose of 1000 mg/kg daily for 14 days did not cause toxicity signs such as death, changes in activity, or piloerection. Since there are no significant differences between treated groups and control groups, hematological and biochemical analysis confirmed safety of the proteolysate (p > 0.05). In addition, there were no significant differences between organs weights of the treated groups and the control groups. Morphologically, neither histopathological changes, nor gross abnormalities were observed. However, the proteolysate caused significant decrease in body weight in relation to the control groups (p ≤ 0.05) probably due to appetite stimulation by the proteolysate, leading to decreased food consumption in sub-acute group. It is concluded that the proteolysate generated from Actinopyga lecanora possess a significant anti-hypertensive effect and would be potentially used as natural alternative of ACE inhibitors.

Keywords: ACE inhibition, Actinopyga lecanora, anti-hypertensive activity, bioactive peptides, normotensive rats

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648 Phytoremediation of Pharmaceutical Emerging Contaminant-Laden Wastewater: A Techno-Economic and Sustainable Development Approach

Authors: Reda A. Elkhyat, Mahmoud Nasr, Amel A. Tammam, Mohamed A. Ghazy

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Pharmaceuticals and personal care products (PPCPs) are a unique group of emerging contaminants continuously introduced into the aquatic ecosystem at concentrations capable of inducing adverse effects on humans and aquatic organisms, even at trace levels ranging from ppt to ppm. Amongst the common pharmaceutical emerging pollutants detected in several aquatic environments, acetaminophen has been recognized for its high toxicity. Once released into the aquatic environment, acetaminophen could be degraded by the microbial community and adsorption/ uptake by the plants. Although many studies have investigated the hazard risks of acetaminophen pollutants on aquatic animals, the number of studies demonstrating its removal efficiency and effects on the aquatic plant still needs to be expanded. In this context, this study aims to apply the aquatic plant-based phytoremediation system to eliminate this emerging contaminant from domestic wastewater. The phytoremediation experiment was performed in a hydroponic system containing Eichhornia crassipes and operated under the natural environment at 25°C to 30°C. This system was subjected to synthetic domestic wastewater with the maximum initial chemical oxygen demand (COD) of 390 mg/L and three different acetaminophen concentrations of 25, 50, and 200 mg/L. After 17 d of operation, the phytoremediation system achieved removal efficiencies of about 100% and 85.6±4.2% for acetaminophen and COD, respectively.Moreover, the Eichhornia crassipes could withstand the toxicity associated with increasing the acetaminophen concentrations from 25 to 200 mg/L. This high treatment performance could be assigned to the well-adaptation of the water hyacinth to the phytoremediation factors. Moreover, it has been proposed that this phytoremediation system could be largely supported by phytodegradation and plant uptaking mechanisms; however, detecting the generated intermediates, metabolites, and degradation products are still under investigation. Applying this free-floating plant in wastewater treatment and reducing emerging contaminants would meet the targets of SDGs 3, 6, and. 14. The cost-benefit analysis was performed for the phytoremediation system. The phytoremediation system is financially viable as the net profit was 2921 US $/ y with a payback period of nine years.

Keywords: domestic wastewater, emerging pollutants, hydrophyte Eichhornia crassipes, paracetamol removal efficiency, sustainable development goals (SDGs)

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647 Carbendazim Toxicity and Ameliorative Effect of Vitamin E in African Giant Rats

Authors: A. O. Omonona, T. A. Jarikre

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Increase specialization in agriculture and use of pesticides may inadvertently cause ecosystem degradation and eventually loss of biodiversity. The populations of numerous wildlife species have undergone a precipitous decline. Many of these problems have been attributed directly to habitat loss and over exploitation resulting from unregulated pesticide uses. Carbendazim a broad spectrum benzimidazole fungicide and a metabolite of benomyl, is used to control plant disease in cereals and fruit. The effect of carbendazim exposure and the ameliorative effect of tocopherol (vitamin E) were assessed on African giant rat AGR. Hematological, biochemical and histological changes were used to determine the health condition of the animals exposed to pesticide. Sixteen AGR were stabilized, weighed and then divided into four experimental groups (A to D). Two groups were pretreated with vitamin. Group A was exposed to carbendazim only, B- carbendazim + vitamin, C- vitamin only, and D- blank (control). Packed cell volume PCV was estimated by the microhematocrit method, Leucocyte and Platelet counts were determined using the hemocytometric method. Cholinesterase (AchE) and markers of oxidative stress were quantified, and tissue changes examined microscopically. There were no behavioral changes observed in the animals, but there was a decrease in body weight and abortion after 23 days of exposure to carbendazim. There was significant differences in the packed cell volume, the hemoglobin concentration and the red blood cell counts (p < 0.05). The increases in malonyl aldehyde MDA was significant (p < 0.05) in the pesticide intoxicated rats compared to control. Vitamin E supplementation reduced MDA level significantly (p < 0.05). There was a sharp remarkable decrease in acetylcholinesterase levels in the pesticide intoxicated rats (p < 0.05). Vitamin E supplementation normalise the AchE levels comparable to that in control. Grossly, the vital organs appeared normal in the pesticide exposed and control groups except moderate pulmonary congestion. Microscopically, there was severe diffuse hepatocellular swelling in carbendazim exposed group. The severity of hepatocellular injury was reduced in the rats with vitamin E. This study ascertained the toxic effect of carbendazim and antioxidative properties of vitamins in the Africa giant rat.

Keywords: African giant rat, antioxidant, carbendazim, pesticides, toxicity

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646 Investigation of Mutagenicity and DNA Binding Properties of Metal-Free and Metallophthalocyanines Containing α-Napththolbenzein Groups on the Peripheral Positions

Authors: Meltem Betül Sağlam, Halil İbrahim Güler, Aykut Sağlam

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In this work, phthalocyanine compounds containing α-naphtholbenzeinunits have been synthesized. Mutagenicity and DNA binding properties of the compounds were investigated by Salmonella/Microsome Assay and spectrophotometer. According to the results of the preliminary range finding tests, the compounds gave no toxic effect to all tester strain S. typhimurium TA98 and TA100 at doses of 500, 1100, 350, 500 and 750 µg/plate in the presence and absence of S9, respectively. This study showed that all compounds exhibited efficient DNA-binding activity. In conclusion, these non-toxic compounds may be used as effective DNA dyes for molecular biology studies.

Keywords: dye, mutagenicity, phthalocyanine, toxicity

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645 Wastewater Treatment Using Ternary Hybrid Advanced Oxidation Processes Through Heterogeneous Fenton

Authors: komal verma, V. S. Moholkar

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In this current study, the challenge of effectively treating and mineralizing industrial wastewater prior to its discharge into natural water bodies, such as rivers and lakes, is being addressed. Particularly, the focus is on the wastewater produced by chemical process industries, including refineries, petrochemicals, fertilizer, pharmaceuticals, pesticides, and dyestuff industries. These wastewaters often contain stubborn organic pollutants that conventional techniques, such as microbial processes cannot efficiently degrade. To tackle this issue, a ternary hybrid technique comprising of adsorption, heterogeneous Fenton process, and sonication has been employed. The study aims to evaluate the effectiveness of this approach for treating and mineralizing wastewater from a fertilizer industry located in Northeast India. The study comprises several key components, starting with the synthesis of the Fe3O4@AC nanocomposite using the co-precipitation method. The nanocomposite is then subjected to comprehensive characterization through various standard techniques, including FTIR, FE-SEM, EDX, TEM, BET surface area analysis, XRD, and magnetic property determination using VSM. Next, the process parameters of wastewater treatment are statistically optimized, focusing on achieving a high level of COD (Chemical Oxygen Demand) removal as the response variable. The Fe3O4@AC nanocomposite's adsorption characteristics and kinetics are also assessed in detail. The remarkable outcome of this study is the successful application of the ternary hybrid technique, combining adsorption, Fenton process, and sonication. This approach proves highly effective, leading to nearly complete mineralization (or TOC removal) of the fertilizer industry wastewater. The results highlight the potential of the Fe3O4@AC nanocomposite and the ternary hybrid technique as a promising solution for tackling challenging wastewater pollutants from various chemical process industries. This paper reports investigations in the mineralization of industrial wastewater (COD = 3246 mg/L, TOC = 2500 mg/L) using a ternary (ultrasound + Fenton + adsorption) hybrid advanced oxidation process. Fe3O4 decorated activated charcoal (Fe3O4@AC) nanocomposites (surface area = 538.88 m2/g; adsorption capacity = 294.31 mg/g) were synthesized using co-precipitation. The wastewater treatment process was optimized using central composite statistical design. At optimum conditions, viz. pH = 4.2, H2O2 loading = 0.71 M, adsorbent dose = 0.34 g/L, reduction in COD and TOC of wastewater were 94.75% and 89%, respectively. This result results from synergistic interactions among the adsorption of pollutants onto activated charcoal and surface Fenton reactions induced due to the leaching of Fe2+/Fe3+ ions from the Fe3O4 nanoparticles. Micro-convection generated due to sonication assisted faster mass transport (adsorption/desorption) of pollutants between Fe3O4@AC nanocomposite and the solution. The net result of this synergism was high interactions and reactions among and radicals and pollutants that resulted in the effective mineralization of wastewater. The Fe3O4@AC showed excellent recovery (> 90 wt%) and reusability (> 90% COD removal) in 5 successive cycles of treatment. LC-MS analysis revealed effective (> 50%) degradation of more than 25 significant contaminants (in the form of herbicides and pesticides) after the treatment with ternary hybrid AOP. Similarly, the toxicity analysis test using the seed germination technique revealed ~ 60% reduction in the toxicity of the wastewater after treatment.

Keywords: chemical oxygen demand (cod), fe3o4@ac nanocomposite, kinetics, lc-ms, rsm, toxicity

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644 Influence of Smoking on Fine And Ultrafine Air Pollution Pm in Their Pulmonary Genetic and Epigenetic Toxicity

Authors: Y. Landkocz, C. Lepers, P.J. Martin, B. Fougère, F. Roy Saint-Georges. A. Verdin, F. Cazier, F. Ledoux, D. Courcot, F. Sichel, P. Gosset, P. Shirali, S. Billet

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In 2013, the International Agency for Research on Cancer (IARC) classified air pollution and fine particles as carcinogenic to humans. Causal relationships exist between elevated ambient levels of airborne particles and increase of mortality and morbidity including pulmonary diseases, like lung cancer. However, due to a double complexity of both physicochemical Particulate Matter (PM) properties and tumor mechanistic processes, mechanisms of action remain not fully elucidated. Furthermore, because of several common properties between air pollution PM and tobacco smoke, like the same route of exposure and chemical composition, potential mechanisms of synergy could exist. Therefore, smoking could be an aggravating factor of the particles toxicity. In order to identify some mechanisms of action of particles according to their size, two samples of PM were collected: PM0.03 2.5 and PM0.33 2.5 in the urban-industrial area of Dunkerque. The overall cytotoxicity of the fine particles was determined on human bronchial cells (BEAS-2B). Toxicological study focused then on the metabolic activation of the organic compounds coated onto PM and some genetic and epigenetic changes induced on a co-culture model of BEAS-2B and alveolar macrophages isolated from bronchoalveolar lavages performed in smokers and non-smokers. The results showed (i) the contribution of the ultrafine fraction of atmospheric particles to genotoxic (eg. DNA double-strand breaks) and epigenetic mechanisms (eg. promoter methylation) involved in tumor processes, and (ii) the influence of smoking on the cellular response. Three main conclusions can be discussed. First, our results showed the ability of the particles to induce deleterious effects potentially involved in the stages of initiation and promotion of carcinogenesis. The second conclusion is that smoking affects the nature of the induced genotoxic effects. Finally, the in vitro developed cell model, using bronchial epithelial cells and alveolar macrophages can take into account quite realistically, some of the existing cell interactions existing in the lung.

Keywords: air pollution, fine and ultrafine particles, genotoxic and epigenetic alterations, smoking

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643 Caffeic Acid in Cosmetic Formulations: An Innovative Assessment

Authors: Caroline M. Spagnol, Vera L. B. Isaac, Marcos A. Corrêa, Hérida R. N. Salgado

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Phenolic compounds are abundant in the Brazilian plant kingdom and they are part of a large and complex group of organic substances. Cinnamic acids are part of this group of organic compounds, and caffeic acid (CA) is one of its representatives. Antioxidants are compounds which act as free radical scavengers and, in other cases, such as metal chelators, both in the initiation stage and the propagation of oxidative process. The tyrosinase, polyphenol oxidase, is an enzyme that acts at various stages of melanin biosynthesis within the melanocytes and is considered a key molecule in this process. Some phenolic compounds exhibit inhibitory effects on melanogenesis by inhibiting the tyrosinase enzymatic activity and therefore has been the subject of studies. However, few studies have reported the effectiveness of these products and their safety. Objectives: To assess the inhibitory activity of tyrosinase, the antioxidant activity of CA and its cytotoxic potential. The method to evaluate the inhibitory activity of tyrosinase aims to assess the reduction transformation of L-dopa into dopaquinone reactions catalyzed by the enzyme. For evaluating the antioxidant activity was used the analytical methodology of DPPH radical inhibition. The cytotoxicity evaluation was carried out using the MTT method (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide), a colorimetric assay which determines the amount of insoluble violet crystals formed by the reduction of MTT in the mitochondria of living cells. Based on the results obtained during the study, CA has low activity as a depigmenting agent. However, it is a more potent antioxidant than ascorbic acid (AA), since a lower amount of CA is sufficient to inhibit 50% of DPPH radical. The results are promising since CA concentration that promoted 50% toxicity in HepG2 cells (IC50=781.8 μg/mL) is approximately 330 to 400 times greater than the concentration required to inhibit 50% of DPPH (IC50 DPPH= 2.39 μg/mL) and ABTS (IC50 ABTS= 1.96 μg/mL) radicals scavenging activity, respectively. The maximum concentration of caffeic acid tested (1140 mg /mL) did not reach 50% of cell death in HaCat cells. Thus, it was concluded that the caffeic acid does not cause toxicity in HepG2 and HaCat cells in the concentrations required to promote antioxidant activity in vitro, and it can be applied in topical products.

Keywords: caffeic acid, antioxidant, cytotoxicity, cosmetic

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642 Acute and Subacute Toxicity of the Aqueous Extract of the Bark Stems of Balanites aegyptiaca (L.) Delile in Wistar Rats

Authors: Brahim Sow

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Background: Throughout West Africa, Balanites aegyptiaca (BA), or Zygophyllaceae, is widely used in traditional medicine to treat diabetes, hypertension, inflammation, malaria and liver disorders. In our recent research, we found that BA has nephroprotective potential against diabetes mellitus, hypertension and kidney disorders. However, to our knowledge, no systematic studies have been carried out on its derivative (toxicity) profile. Aim of the study: The study was conducted to assess the potential potency of the hydroalcoholic extract of BA bark in rats by the acute and sub-acute oral route. Materials and methods: Male and female rats in the acute depression study received BA extract orally at single doses of 500 mg/kg, 2000 mg/kg, 3000 mg/kg and 5000 mg/kg (n = 6 per group/sex). To assess acute depression, abnormal behaviour, toxic symptoms, weight and death were observed for 14 consecutive days. For the subacute impairment study, Wistar rats received the extract orally at doses of 125, 250 and 500 mg/kg (n=6 per group/sex) per day for 28 days. Behaviour and body weight were monitored daily. At the end of the treatment period, biochemical, haematological and histopathological examinations were performed, and gross and histopathological examinations of several organs were carried out. To determine the presence or absence of phytochemicals, the BA extract was subjected to gage phage chromatographic examination. Results: The absence of absorption chromatography of BA indicates the absence of cyanide groups. This suggests that the BA extract does not contain toxic substances. No mortality or adverse effects were observed at 5000 mg/kg in the acute depression test. With regard to body weight, general behaviour, relative organ weights, haematological and biochemical parameters, BA extract did not induce any mortality or potentially treatment-related effects in the sub-acute study. The normal architecture of the vital organs was revealed by histopathological examination, indicating the absence of morphological alterations. Conclusion: BA extract administered orally for 28 days at doses up to 500 mg/kg did not cause toxicological damage in rats in the present study. The median lethal dose (LD50) of the extract was estimated to be over 5000 mg/kg in an acute hyperglycaemia study.

Keywords: Balanites aegyptiaca L Delile, haematology, biochemistry, rat

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641 Factors Affecting Treatment Resilience in Patients with Oesophago-Gastric Cancers Undergoing Palliative Chemotherapy: A Literature Review

Authors: Kiran Datta, Daniella Holland-Hart, Anthony Byrne

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Introduction: Oesophago-gastric (OG) cancers are the fifth commonest in the UK, accounting for over 12,000 deaths each year. Most patients will present at later stages of the disease, with only 21% of patients with stage 4 disease surviving longer than a year. As a result, many patients are unsuitable for curative surgery and instead receive palliative treatment to improve prognosis and symptom burden. However, palliative chemotherapy can result in significant toxicity: almost half of the patients are unable to complete their chemotherapy regimen, with this proportion rising significantly in older and frailer patients. In addition, clinical trials often exclude older and frailer patients due to strict inclusion criteria, meaning there is limited evidence to guide which patients are most likely to benefit from palliative chemotherapy. Inappropriate chemotherapy administration is at odds with the goals of palliative treatment and care, which are to improve quality of life, and this also represents a significant resource expenditure. This literature review aimed to examine and appraise evidence regarding treatment resilience in order to guide clinicians in identifying the most suitable candidates for palliative chemotherapy. Factors influencing treatment resilience were assessed, as measured by completion rates, dose reductions, and toxicities. Methods: This literature review was conducted using rapid review methodology, utilising modified systematic methods. A literature search was performed across the MEDLINE, EMBASE, and Cochrane Library databases, with results limited to papers within the last 15 years and available in English. Key inclusion criteria included: 1) participants with either oesophageal, gastro-oesophageal junction, or gastric cancers; 2) patients treated with palliative chemotherapy; 3) available data evaluating the association between baseline participant characteristics and treatment resilience. Results: Of the 2326 papers returned, 11 reports of 10 studies were included in this review after excluding duplicates and irrelevant papers. Treatment resilience factors that were assessed included: age, performance status, frailty, inflammatory markers, and sarcopenia. Age was generally a poor predictor for how well patients would tolerate chemotherapy, while poor performance status was a better indicator of the need for dose reduction and treatment non-completion. Frailty was assessed across one cohort using multiple screening tools and was an effective marker of the risk of toxicity and the requirement for dose reduction. Inflammatory markers included lymphopenia and the Glasgow Prognostic Score, which assessed inflammation and hypoalbuminaemia. Although quick to obtain and interpret, these findings appeared less reliable due to the inclusion of patients treated with palliative radiotherapy. Sarcopenia and body composition were often associated with chemotherapy toxicity but not the rate of regimen completion. Conclusion: This review demonstrates that there are numerous measures that can estimate the ability of patients with oesophago-gastric cancer to tolerate palliative chemotherapy, and these should be incorporated into clinical assessments to promote personalised decision-making around treatment. Age should not be a barrier to receiving chemotherapy and older and frailer patients should be included in future clinical trials to better represent typical patients with oesophago-gastric cancers. Decisions regarding palliative treatment should be guided by these factors identified as well as patient preference.

Keywords: frailty, oesophago-gastric cancer, palliative chemotherapy, treatment resilience

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640 T3P® -DMSO Mediated One-Pot Tandem Approach for the Synthesis of 3,4-Dihydropyrimidin-2(1H)-Ones/Thiones from Alcohols

Authors: Vinaya Kambappa

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Propylphosphonic anhydride (T3P®)-DMSO is used as an efficient and mild reagent for the one-pot synthesis of 3,4-dihydropyrimidin-2(1H)-ones/thiones from aromatic alcohols. Alcohols are oxidized in situ to aldehydes under mild conditions, which in turn undergo a three-component reaction with β-ketoester and urea/thiourea to afford 3,4-dihydropyrimidin-2(1H)-ones/thiones. The synthesis of 3,4-dihydropyrimidin-2(1H)-ones/thiones directly from alcohols has been reported for the first time best to our knowledge, under mild reaction conditions in good yield. The easy work-up procedure, low cost and less toxicity of the reagent are the main advantages of this protocol.

Keywords: β-ketoester, propylphosphonic anhydride, three-component reaction, pyrimidine

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639 Embryotoxicity of Nano-Iron Oxide (Fe2O3) to Bio-Indicator of Pollution of Land Helix Aspersa

Authors: S. Besnaci, S. Bensoltane, H. Locif, S. Saadi

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To validate an ecotoxicological approach to assessing toxicological effects caused by the oxide powder of nano-iron Fe2O3, we searched in the ecotoxicology laboratory cell bodies bio accumulators and bio-indicators of soil pollution the snail Helix aspersa. In this study, we evaluated the toxicity of nano Fe2O3 during a very sensitive phase of development H.aspersa (embryonic stage). During embryonic development, we observed in treated with various concentrations of nano Fe2O3 (1.25 g/l, 1.5 g/l, and 2 g/l) compared to control, the deformation of the membrane of the egg and accumulation of this molecule at the rear of the egg proven by the photographs, as with the influence on the hatching percentage.

Keywords: eggs, embryotoxicity, Fe2O3, Helix aspersa, nanoparticles

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638 Efficacy of Agrobacterium Tumefaciens as a Possible Entomopathogenic Agent

Authors: Fouzia Qamar, Shahida Hasnain

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The objective of the present study was to evaluate the possible role of Agrobacterium tumefaciens as a possible insect biocontrol agent. Pests selected for the present challenge were adult males of Periplaneta americana and last instar larvae of Pieris brassicae and Spodoptera litura. Different ranges of bacterial doses were selected and tested to score the mortalities of the insects after 24 hours, for the lethal dose estimation studies. Mode of application for the inoculation of the bacteria, was the microinjection technique. The evaluation of the possible entomopathogenic carrying attribute of bacterial Ti plasmid, led to the conclusion that the loss of plasmid was associated with the loss of virulence against target insects.

Keywords: agrobacterium tumefaciens, toxicity assessment, biopesticidal attribute, entomopathogenic agent

Procedia PDF Downloads 349
637 Chronic Impact of Silver Nanoparticle on Aerobic Wastewater Biofilm

Authors: Sanaz Alizadeh, Yves Comeau, Arshath Abdul Rahim, Sunhasis Ghoshal

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The application of silver nanoparticles (AgNPs) in personal care products, various household and industrial products has resulted in an inevitable environmental exposure of such engineered nanoparticles (ENPs). Ag ENPs, released via household and industrial wastes, reach water resource recovery facilities (WRRFs), yet the fate and transport of ENPs in WRRFs and their potential risk in the biological wastewater processes are poorly understood. Accordingly, our main objective was to elucidate the impact of long-term continuous exposure to AgNPs on biological activity of aerobic wastewater biofilm. The fate, transport and toxicity of 10 μg.L-1and 100 μg.L-1 PVP-stabilized AgNPs (50 nm) were evaluated in an attached growth biological treatment process, using lab-scale moving bed bioreactors (MBBRs). Two MBBR systems for organic matter removal were fed with a synthetic influent and operated at a hydraulic retention time (HRT) of 180 min and 60% volumetric filling ratio of Anox-K5 carriers with specific surface area of 800 m2/m3. Both reactors were operated for 85 days after reaching steady state conditions to develop a mature biofilm. The impact of AgNPs on the biological performance of the MBBRs was characterized over a period of 64 days in terms of the filtered biodegradable COD (SCOD) removal efficiency, the biofilm viability and key enzymatic activities (α-glucosidase and protease). The AgNPs were quantitatively characterized using single-particle inductively coupled plasma mass spectroscopy (spICP-MS), determining simultaneously the particle size distribution, particle concentration and dissolved silver content in influent, bioreactor and effluent samples. The generation of reactive oxygen species and the oxidative stress were assessed as the proposed toxicity mechanism of AgNPs. Results indicated that a low concentration of AgNPs (10 μg.L-1) did not significantly affect the SCOD removal efficiency whereas a significant reduction in treatment efficiency (37%) was observed at 100 μg.L-1AgNPs. Neither the viability nor the enzymatic activities of biofilm were affected at 10 μg.L-1AgNPs but a higher concentration of AgNPs induced cell membrane integrity damage resulting in 31% loss of viability and reduced α-glucosidase and protease enzymatic activities by 31% and 29%, respectively, over the 64-day exposure period. The elevated intercellular ROS in biofilm at a higher AgNPs concentration over time was consistent with a reduced biological biofilm performance, confirming the occurrence of a nanoparticle-induced oxidative stress in the heterotrophic biofilm. The spICP-MS analysis demonstrated a decrease in the nanoparticles concentration over the first 25 days, indicating a significant partitioning of AgNPs into the biofilm matrix in both reactors. The concentration of nanoparticles increased in effluent of both reactors after 25 days, however, indicating a decreased retention capacity of AgNPs in biofilm. The observed significant detachment of biofilm also contributed to a higher release of nanoparticles due to cell-wall destabilizing properties of AgNPs as an antimicrobial agent. The removal efficiency of PVP-AgNPs and the biofilm biological responses were a function of nanoparticle concentration and exposure time. This study contributes to a better understanding of the fate and behavior of AgNPs in biological wastewater processes, providing key information that can be used to predict the environmental risks of ENPs in aquatic ecosystems.

Keywords: biofilm, silver nanoparticle, single particle ICP-MS, toxicity, wastewater

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636 Virtual Screening and in Silico Toxicity Property Prediction of Compounds against Mycobacterium tuberculosis Lipoate Protein Ligase B (LipB)

Authors: Junie B. Billones, Maria Constancia O. Carrillo, Voltaire G. Organo, Stephani Joy Y. Macalino, Inno A. Emnacen, Jamie Bernadette A. Sy

Abstract:

The drug discovery and development process is generally known to be a very lengthy and labor-intensive process. Therefore, in order to be able to deliver prompt and effective responses to cure certain diseases, there is an urgent need to reduce the time and resources needed to design, develop, and optimize potential drugs. Computer-aided drug design (CADD) is able to alleviate this issue by applying computational power in order to streamline the whole drug discovery process, starting from target identification to lead optimization. This drug design approach can be predominantly applied to diseases that cause major public health concerns, such as tuberculosis. Hitherto, there has been no concrete cure for this disease, especially with the continuing emergence of drug resistant strains. In this study, CADD is employed for tuberculosis by first identifying a key enzyme in the mycobacterium’s metabolic pathway that would make a good drug target. One such potential target is the lipoate protein ligase B enzyme (LipB), which is a key enzyme in the M. tuberculosis metabolic pathway involved in the biosynthesis of the lipoic acid cofactor. Its expression is considerably up-regulated in patients with multi-drug resistant tuberculosis (MDR-TB) and it has no known back-up mechanism that can take over its function when inhibited, making it an extremely attractive target. Using cutting-edge computational methods, compounds from AnalytiCon Discovery Natural Derivatives database were screened and docked against the LipB enzyme in order to rank them based on their binding affinities. Compounds which have better binding affinities than LipB’s known inhibitor, decanoic acid, were subjected to in silico toxicity evaluation using the ADMET and TOPKAT protocols. Out of the 31,692 compounds in the database, 112 of these showed better binding energies than decanoic acid. Furthermore, 12 out of the 112 compounds showed highly promising ADMET and TOPKAT properties. Future studies involving in vitro or in vivo bioassays may be done to further confirm the therapeutic efficacy of these 12 compounds, which eventually may then lead to a novel class of anti-tuberculosis drugs.

Keywords: pharmacophore, molecular docking, lipoate protein ligase B (LipB), ADMET, TOPKAT

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635 BTEX (Benzene, Toluene, Ethylbenzene and Xylene) Degradation by Cold Plasma

Authors: Anelise Leal Vieira Cubas, Marina de Medeiros Machado, Marília de Medeiros Machado

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The volatile organic compounds - BTEX (Benzene, Toluene, Ethylbenzene, and Xylene) petroleum derivatives, have high rates of toxicity, which may carry consequences for human health, biota and environment. In this direction, this paper proposes a method of treatment of these compounds by using corona discharge plasma technology. The efficiency of the method was tested by analyzing samples of BTEX after going through a plasma reactor by gas chromatography method. The results show that the optimal residence time of the sample in the reactor was 8 minutes.

Keywords: BTEX, degradation, cold plasma, ecological sciences

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634 The Determination of Co, Cd and Pb in Seafoods of Thewet Market, Bangkok to Develop Quality of Life of Consumer

Authors: Chinnawat Satsananan

Abstract:

The amount of heavy metals in our environment has been of great concern because of their toxicity when their concentration is more than the permissible level. These metals enter the environment by different ways such as industrial activities, soil pollution. We have used flame atomic absorption spectrometry technique for determination of the concentration of Co, Cd and Pb in different tissues of five samples of seafoods (mackerel, squid, mussels, scallops and shrimp). The concentrations of Co, Cd and Pb in all examined seafoods were less than the reported literature values (WHO). The results mentioned that the seafoods obtained from Thewet Market were safety to consumption and make the quality of life of people in the community look better.

Keywords: heavy metals, seafood, atomic absorption spectrometry, Bangkok

Procedia PDF Downloads 298
633 Heavy Metals among Female Adolescents Attending Secondary Schools in Kano, Nigeria

Authors: I. Yunusa, M. A. Ibrahim, A. H. Yakasai, L. U. S. Ezeanyika

Abstract:

This study was conducted to examine the level of heavy metals among 192 apparently healthy female adolescents randomly selected from three different boarding secondary schools in the urban area of the most populated city in north-western part of Nigeria. Atomic absorption spectrometry (AAS) was used to determine the plasma levels of the heavy metals which include cadmium (Cd), cobalt (Co), chromium (Cr), copper (Cu), iron (Fe), manganese (Mn), molybdenum (Mo), nickel (Ni), lead (Pb) and zinc (Zn). Our findings revealed the following mean±SD values for each of the heavy metal; 0.11±0.01µg Cd/L, 0.09 ± 0.02µg Co/L, 0.19 ± 0.02 µg Cr/L, 0.91 ± 0.02 µg Cu/L, 1.53 ± 0.31 µg Fe/L, 0.01 ± 0.04 µg Mn/L, 0.3.8 ± 0.04µg Mo/L, 0.04±0.01µg Ni/L, 0.04 ± 0.01µg Pb/L and 2.80 ± 0.24µg Zn/L respectively. It was concluded that toxicity from heavy metals did not exist among female adolescents.

Keywords: heavy metals, female, adolescents, Nigeria

Procedia PDF Downloads 355
632 Evaluation of the Effect of Magnetic Field on Fibroblast Attachment in Contact with PHB/Iron Oxide Nanocomposite

Authors: Shokooh Moghadam, Mohammad Taghi Khorasani, Sajjad Seifi Mofarah, M. Daliri

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Through the recent two decades, the use of magnetic-property materials with the aim of target cell’s separation and eventually cancer treatment has incredibly increased. Numerous factors can alter the efficacy of this method on curing. In this project, the effect of magnetic field on adhesion of PDL and L929 cells on nanocomposite of iron oxide/PHB with different density of iron oxides (1%, 2.5%, 5%) has been studied. The nanocamposite mentioned includes a polymeric film of poly hydroxyl butyrate and γ-Fe2O3 particles with the average size of 25 nanometer dispersed in it and during this process, poly vinyl alcohol with 98% hydrolyzed and 78000 molecular weight was used as an emulsion to achieve uniform distribution. In order to get the homogenous film, the solution of PHB and iron oxide nanoparticles were put in a dry freezer and in liquid nitrogen, which resulted in a uniform porous scaffold and for removing porosities a 100◦C press was used. After the synthesis of a desirable nanocomposite film, many different tests were performed, First, the particles size and their distribution in the film were evaluated by transmission electron microscopy (TEM) and even FTIR analysis and DMTA test were run in order to observe and accredit the chemical connections and mechanical properties of nanocomposites respectively. By comparing the graphs of case and control samples, it was established that adding nano particles caused an increase in crystallization temperature and the more density of γ-Fe2O3 lead to more Tg (glass temperature). Furthermore, its dispersion range and dumping property of samples were raised up. Moreover, the toxicity, morphologic changes and adhesion of fibroblast and cancer cells were evaluated by a variety of tests. All samples were grown in different density and in contact with cells for 24 and 48 hours within the magnetic fields of 2×10^-3 Tesla. After 48 hours, the samples were photographed with an optic and SEM and no sign of toxicity was traced. The number of cancer cells in the case of sample group was fairly more than the control group. However, there are many gaps and unclear aspects to use magnetic field and their effects in cancer and all diseases treatments yet to be discovered, not to neglect that there have been prominent step on this way in these recent years and we hope this project can be at least a minimum movement in this issue.

Keywords: nanocomposite, cell attachment, magnetic field, cytotoxicity

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631 Computational Approach to Identify Novel Chemotherapeutic Agents against Multiple Sclerosis

Authors: Syed Asif Hassan, Tabrej Khan

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Multiple sclerosis (MS) is a chronic demyelinating autoimmune disorder, of the central nervous system (CNS). In the present scenario, the current therapies either do not halt the progression of the disease or have side effects which limit the usage of current Disease Modifying Therapies (DMTs) for a longer period of time. Therefore, keeping the current treatment failure schema, we are focusing on screening novel analogues of the available DMTs that specifically bind and inhibit the Sphingosine1-phosphate receptor1 (S1PR1) thereby hindering the lymphocyte propagation toward CNS. The novel drug-like analogs molecule will decrease the frequency of relapses (recurrence of the symptoms associated with MS) with higher efficacy and lower toxicity to human system. In this study, an integrated approach involving ligand-based virtual screening protocol (Ultrafast Shape Recognition with CREDO Atom Types (USRCAT)) to identify the non-toxic drug like analogs of the approved DMTs were employed. The potency of the drug-like analog molecules to cross the Blood Brain Barrier (BBB) was estimated. Besides, molecular docking and simulation using Auto Dock Vina 1.1.2 and GOLD 3.01 were performed using the X-ray crystal structure of Mtb LprG protein to calculate the affinity and specificity of the analogs with the given LprG protein. The docking results were further confirmed by DSX (DrugScore eXtented), a robust program to evaluate the binding energy of ligands bound to the ligand binding domain of the Mtb LprG lipoprotein. The ligand, which has a higher hypothetical affinity, also has greater negative value. Further, the non-specific ligands were screened out using the structural filter proposed by Baell and Holloway. Based on the USRCAT, Lipinski’s values, toxicity and BBB analysis, the drug-like analogs of fingolimod and BG-12 showed that RTL and CHEMBL1771640, respectively are non-toxic and permeable to BBB. The successful docking and DSX analysis showed that RTL and CHEMBL1771640 could bind to the binding pocket of S1PR1 receptor protein of human with greater affinity than as compared to their parent compound (Fingolimod). In this study, we also found that all the drug-like analogs of the standard MS drugs passed the Bell and Holloway filter.

Keywords: antagonist, binding affinity, chemotherapeutics, drug-like, multiple sclerosis, S1PR1 receptor protein

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630 Aquaporin-1 as a Differential Marker in Toxicant-Induced Lung Injury

Authors: Ekta Yadav, Sukanta Bhattacharya, Brijesh Yadav, Ariel Hus, Jagjit Yadav

Abstract:

Background and Significance: Respiratory exposure to toxicants (chemicals or particulates) causes disruption of lung homeostasis leading to lung toxicity/injury manifested as pulmonary inflammation, edema, and/or other effects depending on the type and extent of exposure. This emphasizes the need for investigating toxicant type-specific mechanisms to understand therapeutic targets. Aquaporins, aka water channels, are known to play a role in lung homeostasis. Particularly, the two major lung aquaporins AQP5 and AQP1 expressed in alveolar epithelial and vasculature endothelia respectively allow for movement of the fluid between the alveolar air space and the associated vasculature. In view of this, the current study is focused on understanding the regulation of lung aquaporins and other targets during inhalation exposure to toxic chemicals (Cigarette smoke chemicals) versus toxic particles (Carbon nanoparticles) or co-exposures to understand their relevance as markers of injury and intervention. Methodologies: C57BL/6 mice (5-7 weeks old) were used in this study following an approved protocol by the University of Cincinnati Institutional Animal Care and Use Committee (IACUC). The mice were exposed via oropharyngeal aspiration to multiwall carbon nanotube (MWCNT) particles suspension once (33 ugs/mouse) followed by housing for four weeks or to Cigarette smoke Extract (CSE) using a daily dose of 30µl/mouse for four weeks, or to co-exposure using the combined regime. Control groups received vehicles following the same dosing schedule. Lung toxicity/injury was assessed in terms of homeostasis changes in the lung tissue and lumen. Exposed lungs were analyzed for transcriptional expression of specific targets (AQPs, surfactant protein A, Mucin 5b) in relation to tissue homeostasis. Total RNA from lungs extracted using TRIreagent kit was analyzed using qRT-PCR based on gene-specific primers. Total protein in bronchoalveolar lavage (BAL) fluid was determined by the DC protein estimation kit (BioRad). GraphPad Prism 5.0 (La Jolla, CA, USA) was used for all analyses. Major findings: CNT exposure alone or as co-exposure with CSE increased the total protein content in the BAL fluid (lung lumen rinse), implying compromised membrane integrity and cellular infiltration in the lung alveoli. In contrast, CSE showed no significant effect. AQP1, required for water transport across membranes of endothelial cells in lungs, was significantly upregulated in CNT exposure but downregulated in CSE exposure and showed an intermediate level of expression for the co-exposure group. Both CNT and CSE exposures had significant downregulating effects on Muc5b, and SP-A expression and the co-exposure showed either no significant effect (Muc5b) or significant downregulating effect (SP-A), suggesting an increased propensity for infection in the exposed lungs. Conclusions: The current study based on the lung toxicity mouse model showed that both toxicant types, particles (CNT) versus chemicals (CSE), cause similar downregulation of lung innate defense targets (SP-A, Muc5b) and mostly a summative effect when presented as co-exposure. However, the two toxicant types show differential induction of aquaporin-1 coinciding with the corresponding differential damage to alveolar integrity (vascular permeability). Interestingly, this implies the potential of AQP1 as a differential marker of toxicant type-specific lung injury.

Keywords: aquaporin, gene expression, lung injury, toxicant exposure

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629 Relevance of Dosing Time for Everolimus Toxicity on Thyroid Gland and Hormones in Mice

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

Abstract:

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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628 Preparation of IPNs and Effect of Swift Heavy Ions Irradiation on their Physico-Chemical Properties

Authors: B. S Kaith, K. Sharma, V. Kumar, S. Kalia

Abstract:

Superabsorbent are three-dimensional networks of linear or branched polymeric chains which can uptake large volume of biological fluids. The ability is due to the presence of functional groups like –NH2, -COOH and –OH. Such cross-linked products based on natural materials, such as cellulose, starch, dextran, gum and chitosan, because of their easy availability, low production cost, non-toxicity and biodegradability have attracted the attention of Scientists and Technologists all over the world. Since natural polymers have better biocompatibility and are non-toxic than most synthetic one, therefore, such materials can be applied in the preparation of controlled drug delivery devices, biosensors, tissue engineering, contact lenses, soil conditioning, removal of heavy metal ions and dyes. Gums are natural potential antioxidants and are used as food additives. They have excellent properties like high solubility, pH stability, non-toxicity and gelling characteristics. Till date lot of methods have been applied for the synthesis and modifications of cross-linked materials with improved properties suitable for different applications. It is well known that ion beam irradiation can play a crucial role to synthesize, modify, crosslink or degrade polymeric materials. High energetic heavy ions irradiation on polymer film induces significant changes like chain scission, cross-linking, structural changes, amorphization and degradation in bulk. Various researchers reported the effects of low and heavy ion irradiation on the properties of polymeric materials and observed significant improvement in optical, electrical, chemical, thermal and dielectric properties. Moreover, modifications induced in the materials mainly depend on the structure, the ion beam parameters like energy, linear energy transfer, fluence, mass, charge and the nature of the target material. Ion-beam irradiation is a useful technique for improving the surface properties of biodegradable polymers without missing the bulk properties. Therefore, a considerable interest has been grown to study the effects of SHIs irradiation on the properties of synthesized semi-IPNs and IPNs. The present work deals with the preparation of semi-IPNs and IPNs and impact of SHI like O7+ and Ni9+ irradiation on optical, chemical, structural, morphological and thermal properties along with impact on different applications. The results have been discussed on the basis of Linear Energy Transfer (LET) of the ions.

Keywords: adsorbent, gel, IPNs, semi-IPNs

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627 Neuropharmacological and Neurochemical Evaluation of Methanolic Extract of Elaeocarpus sphaericus (Gaertn.) Stem Bark by Using Multiple Behaviour Models of Mice

Authors: Jaspreet Kaur, Parminder Nain, Vipin Saini, Sumitra Dahiya

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Elaeocarpus sphaericus has been traditionally used in the Indian traditional medicine system for the treatment of stress, anxiety, depression, palpitation, epilepsy, migraine and lack of concentration. The study was investigated to evaluate the neurological potential such as anxiolytic, muscle relaxant and sedative activity of methanolic extract of Elaeocarpus sphaericus stem bark (MEESSB) in mice. Preliminary phytochemical screening and acute oral toxicity of MEESSB was carried out by using standard methods. The anxiety was induced by employing Elevated Plus-Maze (EPM), Light and Dark Test (LDT), Open Field Test (OFT) and Social Interaction test (SIT). The motor coordination and sedative effect was also observed by using actophotometer, rota-rod apparatus and ketamine-induced sleeping time, respectively. Animals were treated with different doses of MEESSB (i.e.100, 200, 400 and 800 mg/kg orally) and diazepam (2 mg/kg i.p) for 21 days. Brain neurotransmitters like dopamine, serotonin and nor-epinephrine level were estimated by validated methods. Preliminary phytochemical analysis of the extract revealed the presence of tannins, phytosterols, steroids and alkaloids. In the acute toxicity studies, MEESSB was found to be non-toxic and with no mortality. In anxiolytic studies, the different doses of MEESSB showed a significant (p<0.05) effect on EPM and LDT. In OFT and SIT, a significant (p<0.05) increase in ambulation, rearing and social interaction time was observed. In the case of motor coordination activity, the MEESSB does not cause any significant effect on the latency to fall off from the rotarod bar as compared to the control group. Moreover, no significant effects on ketamine-induced sleep latency and total sleeping time induced by ketamine were observed. Results of neurotransmitter estimation revealed the increased concentration of dopamine, whereas the level of serotonin and nor-epinephrine was found to be decreased in the mice brain, with MEESSB at dose 800 mg/kg only. The study has validated the folkloric use of the plant as an anxiolytic in Indian traditional medicine while also suggesting potential usefulness in the treatment of stress and anxiety without causing sedation.

Keywords: anxiolytic, behavior experiments, brain neurotransmitters, elaeocarpus sphaericus

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626 Insecticidal Activity of Extracts Essential Oils of Mentha Rotundifolia

Authors: Bouziane Zehaira

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Essential oils derived from aromatic or medicinal plants have recently proven useful in a variety of fields including the production of medicines, perfumes and foodstuffs. The purpose of this research is to determine the insecticidal activity of essential oils extracted from Mentha rotundifolia species against Aphis fabae. The bioassay used to determine essential oils toxicity to pest insect Aphis fabae revealed a very high effective repellent. The effect with concentrations of 100% and 30% were found to be statistically significant (F=64.800, P<0.0001) with an average of 7.66 and 7, respectively. According to the findings, the plant under consideration is promising as a source of natural pesticides and lends itself well to research in the field of pest control using biochemical alternatives.

Keywords: pest, mentha, activity, effective

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625 Whey Protein: A Noval Protective Agent against Oto-Toxicity Induced by Cis-Platin in Male Rat

Authors: Eitedal Daoud, Reda M.Daoud, Khaled Abdel-Wahhab, Maha M.Saber, Lobna Saber

Abstract:

Background: Cis-platin is a widely used chemotherapeutic drug to treat many malignant disorders including head and neck malignancies. Oto-nephrotxicity is an important and dose - limiting side effect of cis - platin therapy. Nowadays, more attention had been paid to oto-toxicity caused with cis-platin. Aim of the Work: This study was designed to investigate the potential protective effect of Whey protein (WP) against cis-platin induced ototoxicity compared to the effect of N-acetylcysteine (NAC) in rats. Methodology: Male albino rats were randomly divided into 6 groups: untreated rats (control), rats orally treated with whey protein (1g/kg b.w/day) for seven executive days, rats treated orally with N-acetylcysteine (500 mg/kgb.w /day) for seven executive days, rates intoxicated intraperitoneal (ip) with cis- platin (10 mg/kgb.w. once), rats treated with whey protein (1g/kgb.w./day) for seven executive days) followed by one injection (ip) of cis-platin(10 mg/kg b.w.) one hour after the last oral administration of whey protein, rats treated with N- acetylcysteine (for seven executive days followed by one injection (ip) of cis-platin (10 mg/kgb.w) one hour after the last oral administration of N-acetylcysteine. The organ of Corti, the stria vascularis and spiral ganglia were visualized by light microscopy at different magnifications. Results: Cis-platin intoxicated animals showed a significant decrease in serum level of total antioxidant capacity (TAC),with inhibition in the activity of serum glutathione-s transferase(GST) and paraoxonnase-1 (PON-1) in comparison with control. Group treated with either NAC or WP with cis-platin showed significant elevation in the activity of both GST & PON-1 with increased serum level of TAC when compared with cis-platin intoxicated rats. Animals treated with NAC or WP with cis-platin compared to those treated with cis-platin alone showed marked degree of improvement towards control rats as there was significant drop in the serum level of cortecosterone, nitric oxide (NO), and melandialdehyde (MDA).Histopathologic, in NAC pretreated group there was no changes in stria vascularis or spiral ganglia. In group pretreated with WP, there was no histopathologic alteration detected in the organ of Corti and Reissers membrane but oedema and haemorrhage were founded in the stria vascularis in small focal manner. Conclusion: Our finding showed that Whey protein is a natural dietary supplement product proved its ability of protection of anti-oxidant system and the cochlea against cis-platin induced ototoxicity.

Keywords: anti-oxidant, cis-platin, N-acetylcysteine, ototoxicity, whey protein

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