Search results for: sublethal toxicity

Authors: A. Watson, G. Telford, D. I. Pritchard

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Objective: We investigated the immunomodulatory ability of licorice (Glycyrrhiza glabra). Such activities could have value for the management of common immunological diseases in dogs, such as environmental allergy. This study investigated the potential of a Licorice root extract (LRE) to influence the relative expression of Th-1, Th-2, and Th-17 cytokines in canine peripheral blood mononuclear cells (PBMC). Methods: A LRE was prepared using an alcoholic-aqueous-based solvent method. The extract was tested in three in vitro assays using canine leukocytes to determine its toxicity and immunoregulatory profile. Extract toxicity was assessed using the human T-lymphocyte cell line, Jurkat E6.1. The impact of the extract on the proliferation of concanavalin-activated canine PBMC was also determined. Finally, the extract was assessed for its ability to influence cytokine release in activated PBMC, measuring culture medium concentrations of interleukin-17, interferon gamma, and interleukin-4. One-way ANOVA followed by Dunnett’s post-test was used for statistics using concanavalin positive control as reference (p ≤ 0.05). Results: There was evidence that the LRE had specific immunomodulatory properties, causing significant inhibition of IL4 expression over a non-toxic/non-cytostatic concentration range (p < 0.001). In the same cell incubations, there was no significant impact on IL17 nor IFNg over the same non-toxic/non-cytostatic concentration range. Conclusion: The study provides in vitro evidence that LRE preferentially reduces the expression of a Th-2-type cytokine, IL4. The dog population, as with humans, is prone to conditions associated with a Th-2 bias of the immune system, such as environmental allergy. Based on these results, licorice merits further evaluation as a useful immune modulator for such allergic diseases.

Keywords: cytokine, Glycyrrhiza glabra, peripheral blood mononuclear cells, T-cell activation

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Authors: Spira A., Marabelle A., Kientop D., Moser E., Mumm J.

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Background: Both interleukin-2 (IL-2) and interleukin-10 (IL-10) have been extensively studied for their stimulatory function on T cells and their potential to obtain sustainable tumor control in RCC, melanoma, lung, and pancreatic cancer as monotherapy, as well as combination with PD-1 blockers, radiation, and chemotherapy. While approved, IL-2 retains significant toxicity, preventing its widespread use. The significant efforts undertaken to uncouple IL-2 toxicity from its anti-tumor function have been unsuccessful, and early phase clinical safety observed with PEGylated IL-10 was not met in a blinded Phase 3 trial. Deka Biosciences has engineered a novel molecule coupling wild-type IL-2 to a high affinity variant of Epstein Barr Viral (EBV) IL-10 via a scaffold (scFv) that binds to epidermal growth factor receptors (EGFR). This patented molecule, termed DK210 (EGFR), is retained at high levels within the tumor microenvironment for days after dosing. In addition to overlapping and non-redundant anti-tumor function, IL-10 reduces IL-2 mediated cytokine release syndrome risks and inhibits IL-2 mediated T regulatory cell proliferation. Methods: DK210 (EGFR) is being evaluated in an open-label, dose-escalation (Phase 1) study with 5 (0.025-0.3 mg/kg) monotherapy dose levels and (expansion cohorts) in combination with PD-1 blockers, or radiation or chemotherapy in patients with advanced solid tumors overexpressing EGFR. Key eligibility criteria include 1) confirmed progressive disease on at least one line of systemic treatment, 2) EGFR overexpression or amplification documented in histology reports, 3) at least a 4 week or 5 half-lives window since last treatment, and 4) excluding subjects with long QT syndrome, multiple myeloma, multiple sclerosis, myasthenia gravis or uncontrolled infectious, psychiatric, neurologic, or cancer disease. Plasma and tissue samples will be investigated for pharmacodynamic and predictive biomarkers and genetic signatures associated with IFN-gamma secretion, aiming to select subjects for treatment in Phase 2. Conclusion: Through successful coupling of wild-type IL-2 with a high affinity IL-10 and targeting directly to the tumor microenvironment, DK210 (EGFR) has the potential to harness IL-2 and IL-10’s known anti-cancer promise while reducing immunogenicity and toxicity risks enabling safe concomitant cytokine treatment with other anti-cancer modalities.

Keywords: cytokine, EGFR over expression, interleukine-2, interleukine-10, clinical trial

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Authors: Kanika Arora, Madhu Bala

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The small intestine epithelium is highly sensitive and major targets of ionizing radiation. Radiation causes gastrointestinal toxicity either by direct deposition of energy or indirectly (inflammation or bystander effects) generating free radicals and reactive oxygen species. Oxidative stress generated as a result of radiation causes active inflammation within the intestinal mucosa leading to structural and functional impairment of gut epithelial barrier. As a result, there is a loss of tolerance to normal dietary antigens and commensal flora together with exaggerated response to pathogens. Dysbiosis may therefore thought to play a role in radiation enteropathy and can contribute towards radiation induced bowel toxicity. Lactobacilli residing in the gut shares a long conjoined evolutionary history with their hosts and by doing so these organisms have developed an intimate and complex symbiotic relationships. The objective behind this study was to look for the strains with varying resistance to ionizing radiation and to see whether the niche of the bacteria is playing any role in radiation resistance property of bacteria. In this study, we have isolated the Lactobacillus spp. from probiotic preparation and murine gastrointestinal tract, both of which were supposed to be the important source for its isolation. Biochemical characterization did not show a significant difference in the properties, while a significant preference was observed in carbohydrate utilization capacity by the isolates. Effect of ionizing radiations induced by Co60 gamma radiation (10 Gy) on lactobacilli cells was investigated. A cellular survival curve versus absorbed doses was determined. Radiation resistance studies showed that the response of isolates towards cobalt-60 gamma radiation differs from each other and significant decrease in survival was observed in a dose-dependent manner. Thus the present study revealed that the property of radioresistance in Lactobacillus depends upon the source from where they have been isolated.

Keywords: dysbiosis, lactobacillus, mitigation, radiation

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Authors: Petr Daniel Kovarik, Matt Kennedy, James Adams, Ajay Wilson, Andy Burns, Charles Kelly, Malcolm Jackson, Rahul Patil, Shahid Iqbal

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Introduction: Osteoradionecrosis (ORN) is a recognised toxicity of radiotherapy (RT) for head and neck cancer (HNC). Existing literature lacks any generally accepted definition and staging system for this toxicity. Objective: The objective is to analyse the outcome of the surgical and nonsurgical treatments of ORN. Material and Method: Data on 2303 patients treated for HNC with radical or adjuvant RT or RT-chemotherapy from January 2010 - December 2021 were retrospectively analysed. Median follow-up to the whole group of patients was 37 months (range 0–148 months). Results: ORN developed in 185 patients (8.1%). The location of ORN was as follows; mandible=170, maxilla=10, and extra oral cavity=5. Multiple ORNs developed in 7 patients. 5 patients with extra oral cavity ORN were excluded from treatment analysis as the management is different. In 180 patients with oral cavity ORN, median follow-up was 59 months (range 5–148 months). ORN healed in 106 patients, treatment failed in 74 patients (improving=10, stable=43, and deteriorating=21). Median healing time was 14 months (range 3-86 months). Notani staging is available in 158 patients with jaw ORN with no previous surgery to the mandible (Notani class I=56, Notani class II=27, and Notani class III=76). 28 ORN (mandible=27, maxilla=1; Notani class I=23, Notani II=3, Notani III=1) healed spontaneously with a median healing time 7 months (range 3–46 months). In 20 patients, ORN developed after dental extraction, in 1 patient in the neomandible after radical surgery as a part of the primary treatment. In 7 patients, ORN developed and spontaneously healed in irradiated bone with no previous surgical/dental intervention. Radical resection of the ORN (segmentectomy, hemi-mandibulectomy with fibula flap) was performed in 43 patients (all mandible; Notani II=1, Notani III=39, Notani class was not established in 3 patients as ORN developed in the neomandible). 27 patients healed (63%); 15 patients failed (improving=2, stable=5, deteriorating=8). The median time from resection to healing was 6 months (range 2–30 months). 109 patients (mandible=100, maxilla=9; Notani I=3, Notani II=23, Notani III=35, Notani class was not established in 9 patients as ORN developed in the maxilla/neomandible) were treated conservatively using a combination of debridement, antibiotics and Pentoclo. 50 patients healed (46%) with a median healing time 14 months (range 3–70 months), 59 patients are recorded with persistent ORN (improving=8, stable=38, deteriorating=13). Out of 109 patients treated conservatively, 13 patients were treated with Pentoclo only (all mandible; Notani I=6, Notani II=3, Notani III=3, 1 patient with neomandible). In total, 8 patients healed (61.5%), treatment failed in 5 patients (stable=4, deteriorating=1). Median healing time was 14 months (range 4–24 months). Extra orally (n=5), 3 cases of ORN were in the auditory canal and 2 in mastoid. ORN healed in one patient (auditory canal after 32 months. Treatment failed in 4 patients (improving=3, stable=1). Conclusion: The outcome of the treatment of ORN remains in general, poor. Every effort should therefore be made to minimise the risk of development of this devastating toxicity.

Keywords: head and neck cancer, radiotherapy, osteoradionecrosis, treatment outcome

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Authors: Marco Clericuzio, Alfredo Vizzini

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The secondary metabolites of Russulales (one of the main orders of phylum Basidiomycota), have been studied. They are mainly terpenoids, with sesquiterpenes being the most common ones, but also triterpenoids and prenylated phenols have been isolated. We found that classes of specific compounds seem to be often allied to systematic groupings, so that they may have chemotaxonomic significance. Moreover, the ecological implications of such metabolites, as well as their biological activities, are discussed. Lately, we have focused our attention on the anti-arthropod activity of Russula metabolites, in particular on the toxicity against mites and other crop pests.

Keywords: chemotaxonomy, fungi, insecticidal activity, russulales, terpenoids

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Authors: N. Piwpuan, J. Tosalee, N. Phonkerd

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Malachite green (MG), a synthetic dye, is used in industries and aquaculture and also disposed in the effluent. Use of wastewater in irrigation increases due to water shortage. However, wastewater containing dyes, MG, are toxic to biological systems. Therefore, effects of MG on growth of vegetables were evaluated in order to utilize dye-contaminated wastewater for irrigation. In this study, Pak choy (Brassica chinensis) and Chinese convolvulus (Ipomoea aquatica) were grown in growing material (mixture of soil, coconut fiber, and compost) for four weeks and afterward kept watering with 200 ml of tap water containing MG at the concentrations of 0 (control), 1, 2, 10, and 20 mg/L. At harvest, number of leaf and shoot and root dry weight of the treated plants were measured and compared with control. For both species, their biomass values were similar among treatments and did not differ from the control plants (dry weight were 0.6-1.0 and 1.1-1.7 g/plant for B. chinensis and I. aquatica, respectively). B. chinensis treated with 2, 10, and 20 mg/L of MG produced lower number of new leaf and had smaller and shorter leaf compared to control and treatment of 1 mg/L. These results indicate the different responses between plant species, which B. chinensis is more sensitive to contaminant compared to I. aquatica. There was no sign of MG and leucomalachite green (LMG) detected in root and shoot tissues of plants treated with MG at 20 mg/L, tested by thin layer chromatography. After plant harvest, toxicity of the growing material from all treatments was tested on mung beans. Percent germination (83-97%), seedling fresh weight (0.3-0.5 g/plant), and shoot length (11-12.5 cm) were similar to the control. These indicated that contaminant in growing material did not pose detrimental effect on mung beans. Based on these results, the water contaminated with low concentration of MG, such as discharge from aquaculture, may serve as ferti-irrigation water to compensate water shortage.

Keywords: ferti-irrigation, soil toxicity, triphenylmethane dye, wastewater reuse

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Authors: P. Jost, L. Muckova, M. Matula, J. Pejchal, D. Jun, R. Stetina

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Sulfur mustard (bis(2-chlorethyl) sulfide) is highly toxic, chemical warfare agent that has been used in the past in several armed conflicts. Except for the skin, respiratory tract is one of the important routes of exposure. The elucidation and understanding of the mechanism of toxicity of SM have been effort intensive research. The multiple targets character of SM caused cellular damage resulted in activation of many different mechanisms which contribute to cellular response and participate in the final cytopathology effect. In our present work, we compared time-dependent changes in sulfur mustard exposed adult human lung fibroblasts NHLF and lung epithelial alveolar cell line A-549. Cell viability (MTT assay, Calcein-AM assay, and xCELLigence - real-time cell analysis), apoptosis (flow cytometry), mitochondrial membrane potential (Δψm, flow cytometry), reactive oxygen species induction (DC and cell cycle distribution (flow cytometry) were studied. We observed significantly decreased mitochondrial membrane potential and subsequent induction of apoptosis correlating with decreased cellular viability in the sulfur mustard exposed cells. In low concentrations, sulfur mustard-induced S-phase cell cycle arrest, on the other hand, high concentrations, cell cycle phase distribution of sulfur mustard exposed cells resembled cell cycle phase distribution of control group, which implies nonspecific cell cycle inhibition. Epithelial cells A-549 was found as more sensible to sulfur mustard toxicity. Acknowledgements: This work was supported by a long-term organization development plan Medical Aspects of Weapons of Mass Destruction of the Faculty of Military Health Sciences, University of Defence.

Keywords: apoptosis, cell cycle, cytotoxicity, sulfur mustard

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Authors: Mary-Ann N. Jallad, Dalal F. Jaber, Alexander M. Abdelnoor

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Introduction: Current evidence confirms that both innate and adaptive immune systems are capable of recognizing and abolishing malignant cells. The emergence of cancerous tumors in patients is, therefore, an indication that certain cancer cells can resist elimination by the immune system through a process known as “immune evasion”. In fact, cancer cells often exploit regulatory mechanisms to escape immunity. Such mechanisms normally exist to control the immune responses and prohibit exaggerated or autoimmune reactions. Recently, immunotherapies have shown promising yet limited results. Therefore this study investigates several immunotherapeutic combinations and devises a triple immunotherapy which harnesses the innate and acquired immune responses towards the annihilation of malignant cells through overcoming their ability of immune evasion, consequently hampering malignant progression and eliminating established tumors. The aims of the study are to rule out acute/chronic toxic effects of the proposed treatment combinations, to assess the effect of these combinations on tumor growth and survival rates, and to investigate potential mechanisms underlying the phenotypic results through analyzing serum levels of anti-tumor cytokines, angiogenic factors and tumor progression indicator, and the tumor-infiltrating immune-cells populations. Methodology: For toxicity analysis, cancer-free C57BL/6 mice are randomized into 9 groups: Group 1 untreated, group 2 treated with sterile saline (solvent of used treatments), group 3 treated with Monophosphoryl-lipid-A, group 4 with anti-CTLA4-antibodies, group 5 with 1-Methyl-Tryptophan (Indolamine-Dioxygenase-1 inhibitor), group 6 with both MPLA and anti-CTLA4-antibodies, group 7 with both MPLA and 1-MT, group 8 with both anti-CTLA4-antibodies and 1-MT, and group 9 with all three: MPLA, anti-CTLA4-antibodies and 1-MT. Mice are monitored throughout the treatment period and for three following months. At that point, histological sections from their main organs are assessed. For tumor progression and survival analysis, a murine melanoma model is generated by injecting analogous mice with B16F10 melanoma cells. These mice are segregated into the listed nine groups. Their tumor size and survival are monitored. For a depiction of underlying mechanisms, melanoma-bearing mice from each group are sacrificed at several time-points. Sera are tested to assess the levels of Interleukin-12 (IL-12), Vascular-Endothelial-Growth Factor (VEGF), and S100B. Furthermore, tumors are excised for analysis of infiltrated immune cell populations including T-cells, macrophages, natural killer cells and immune-regulatory cells. Results: Toxicity analysis shows that all treated groups present no signs of neither acute nor chronic toxicity. Their appearance and weights were comparable to those of control groups throughout the treatment period and for the following 3 months. Moreover, histological sections from their hearts, kidneys, lungs, and livers were normal. Work is ongoing for completion of the remaining study aims. Conclusion: Toxicity was the major concern for the success of the proposed comprehensive combinational therapy. Data generated so far ruled out any acute or chronic toxic effects. Consequently, ongoing work is quite promising and may significantly contribute to the development of more effective immunotherapeutic strategies for the treatment of cancer patients.

Keywords: cancer immunotherapy, check-point blockade, combination therapy, melanoma

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Authors: Dona Pamoda W. Jayatunga, Veer Bala Gupta, Eugene Hone, Ralph N. Martins

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Being a neurodegenerative disorder, Alzheimer’s disease (AD) affects a majority of the elderly demented worldwide. The key risk factors for AD are age, metabolic syndrome, allele status of APOE gene, head injuries and lifestyle. The progressive nature of AD is characterized by symptoms of multiple cognitive deficits exacerbated over time, leading to death within a decade from clinical diagnosis. However, it is revealed that AD originates via a prodromal phase that spans from one to few decades before symptoms first manifest. The key pathological hallmarks of AD brains are deposition of amyloid beta (Aβ) plaques and neurofibrillary tangles (NFT). However, the yet unknown etiology of the disease fails to distinguish mitochondrial dysfunction between a cause or an outcome. The absence of early diagnosis tools and definite therapies for AD have permitted recruits of nutraceutical-based approaches aimed at reducing the risk of AD by modulating lifestyle or be used as preventive tools during AD prodromal state before widespread neurodegeneration begins. The objective of the present study was to investigate beneficial effects of luteolin, a plant-based flavone compound, against AD. The neuroprotective effects of luteolin on amyloid beta (Aβ) (1-42)-induced neurotoxicity was measured using cultured human neuroblastoma BE(2)-M17 cells. After exposure to 20μM Aβ (1-42) for 48 h, the neuroblastoma cells exhibited marked apoptotic death. Co-treatment of 20μM Aβ (1-42) with luteolin (0.5-5μM) significantly protected the cells against Aβ (1-42)-induced toxicity, as assessed by the MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2(4sulfophenyl)-2H-tetrazolium, inner salt; MTS] reduction assay and the lactate dehydrogenase (LDH) cell death assay. The results suggest that luteolin prevents Aβ (1-42)-induced apoptotic neuronal death. However, further studies are underway to determine its protective mechanisms in AD including the activity against tau hyperphosphorylation and mitochondrial dysfunction.

Keywords: Aβ (1-42)-induced toxicity, Alzheimer’s disease, luteolin, neuroblastoma cells

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Authors: Suhera M. Aburawi, Habiba A. El Jaafari, Soad A. Treesh, Abdulssalam M. Abu-Aisha, Faisal S. Alwaer, Reda A. Eltubuly, Medeha Elghedamsi

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Introduction: Infertility is a source of psychological, and sometimes social, stress on parents who desire to have children. Formaldehyde is used chiefly as disinfectant, preservative and in the chemical synthesis. The medical uses of formaldehyde are limited, but focused especially on laboratory use. Selenium is an essential trace mineral element for human; it is essential for sperm function and male fertility. Selenium deficiency has been linked to reproductive problems in animals. Objectives: To investigate the prophylactic and curative effect of selenium on male infertility induced by formaldehyde using male albino mice. Method: Forty male albino mice were used, weight 25-30 gm. Five groups of male mice (n=8) were used. Group 1 was daily administered water for injection (5ml/kg) for five days, group 2 was daily administered selenium (100 μg/kg) for five days, group 3 was daily administered formaldehyde (30mg/kg) for five days, group 4 (prophylaxis) was daily administered a combination of formaldehyde and selenium for five days, while group 5 (curative) was daily administered formaldehyde for five days followed by daily administration of selenium for the next five days. Intraperitoneal administration was adopted. At the end of the administration, seminal fluid was collected from vas deferens. Sperm count, morphology and motility were scored; histopathological screening of genital system was carried out. SPSS was applied for comparing groups. Results and conclusion: It was found that formaldehyde toxicity did not change the sperm count and percentage of motile sperm; unhealthy sperm was increased, while healthy sperm was decreased. Formaldehyde produces degeneration/damage to the male mice genital system. Selenium alone produce an increase in sperm count, volume of seminal fluid and the percentage of motile sperm. Selenium has prophylactic and curative effects against formaldehyde-induce genital system toxicity. Future work is recommended to find out if selenium protective effect is through antioxidant or other mechanisms.

Keywords: infertility, formaldehyde, selenium, male mice

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Authors: Rashmi Tomar, A. Srinivasan, Nayan K. Mohanty, Arun K. Jain

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Phthalates have been used as additives in industrial products since the 1930s, and are universally considered to be ubiquitous environmental contaminants. The general population is exposed to phthalates through consumer products, as well as diet and medical treatments. Animal studies showing the existence of an association between some phthalates and testicular toxicity have generated public and scientific concern about the potential adverse effects of environmental changes on male reproductive health. Unprecedented declines in fertility rates and semen quality have been reported during the last half of the 20th century in developed countries and increasing interest exists on the potential relationship between exposure to environmental contaminants, including phthalates, and human male reproductive health Studies. Phthalates may be associated with altered endocrine function and adverse effects on male reproductive development and function, but human studies are limited. The aim of the present study was detection of phthalate compounds, estimation of their metabolites in infertile & fertile male. Blood and urine samples were collected from 150 infertile patients & 75 fertile volunteers recruited through Department of Urology, Safdarjung Hospital, New Delhi. Blood have been collected in separate glass tubes from the antecubital vein of the patients, serum have been separate and estimate the phthalate level in serum samples by Gas Chromatography / Mass Spectrometry using NIOSH / OSHA detailed protocol. Urine of Infertile & Fertile Subjects was collected & extracted using solid phase extraction method, analysis by HPLC. In conclusion, to the best of our knowledge the present study based on human is first to show the presence of phthalate in human serum samples and their metabolites in urine samples. Significant differences were observed between several phthalates in infertile and fertile healthy individuals.

Keywords: Gas Chromatography, HPLC, male infertility, phthalates, serum, toxicity, urine

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Authors: Farhat Jabeen, Muhammad Asad

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The study assessed the curative potential of Moringa olifera seeds against copper oxide nanoparticles induced toxicity in Oreochromis mossambicus. In order to investigate the curative potential of M. olifera seeds, firstly we examine its chemical composition, secondary metabolites, and bioactive compounds including hydroxyl-cinnamic acids, flavanols and hydroxybenzoic acids through standard methods and high performance liquid chromatography. In current study, the potential sub-lethal toxic dose of CuO-NPs (0.12 mg/l) was investigated through pilot experiment and three non-lethal doses (low=32, medium=48 and high=96 mg/l) of M. olifera were selected on the basis of its LC50 value for O. mossambicus. The experimental fish, O. mossambicus (n=100 of approximately 20 g each) were procured from Manawan Fisheries Complex, Lahore, and acclimatized for two weeks in glass aquaria. Experiment was conducted in accordance with the guidelines of Institutional Animal Ethics Committee, Government College University Faisalabad, Pakistan. During acclimatization and experimental period, fish received the commercial fish feed at 2.5% body weight daily. In order to assess the curative effect of M. olifera against CuO NPs induced toxicity, O. mossambicus were randomly divided into five groups and were designated as control (C) without any treatment, positive control (G*) exposed to potential toxic dose of CuO-NPs at 0.12 mg/l, and three treated groups namely G1, G2, and G3 co-treated with 0.12 mg/l of CuO-NPs plus different doses of M. olifera seed extract at 32, 48, and 96 mg/l, respectively for 56 days. Fish were exposed to waterborne CuO NPs and M. olifera seed extract. CuO-NPs treatment was ceased after 28 days but the doses of M. olifera were continued for 56 days. Blood was taken after 28 and 56 days through caudal venipuncture. Liver and intestine were taken for oxidative stress and histological studies after 56 days. In M. olifera seeds, moisture contents, crude protein, lipids, carbohydrates and ash were recorded as 3.8, 37.83, 32.52, 46.12, and 7.75%, respectively on dry weight basis. Total energy was recorded as 627.36 kcal/100g. Qualitative analysis of M. olifera seeds showed the presence of terpenoids, saponins, flavonoids, alkaloids and phenolics, while its quantitative analysis showed the considerable amount of total phenolics, flavonoids, saponins, and alkaloids as 134.75, 170.15, 1.57, and 0.4 µg/mg, respectively. Analysis of bioactive compounds in M. olifera seeds showed the presence of hydroxy-cinnamic acids (6.07 µg/ml), flavanols (71.72 µg/ml), and hydroxyl benzoic acids (97.82 µg/ml). The results showed that M. oliefera seed extract at 48 and 56 mg/l was able to cure against the toxic effects of CuO-NPs. The significant changes were observed in G* and G1 for sero-hepatic enzymes, anti-oxidants and histological profile. The investigations of this study showed that M. olifera is a good curative agent against potential induced toxicity of CuO-NPs in O. mossambicus. The curative effect of M. olifera is attributed to the presence of higher amount of secondary metabolites and bioactive compounds. This study suggested the use of M. olifera to curate different ailments in fish and other organisms.

Keywords: CuO nanoparticles, curative, Moringa olifera, Oreochromis mossambicus

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Authors: Yara Saleh, Sebastien Antherieu, Romain Dusautoir, Jules Sotty, Laurent Alleman, Ludivine Canivet, Esperanza Perdrix, Pierre Dubot, Anne Platel, Fabrice Nesslany, Guillaume Garcon, Jean-Marc Lo-Guidice

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Air pollution is one of the leading causes of premature death worldwide. Among air pollutants, particulate matter (PM) is a major health risk factor, through the induction of cardiopulmonary diseases and lung cancers. They are composed of coarse, fine and ultrafine particles (PM10, PM2.5, and PM0.1 respectively). Ultrafine particles are emerging unregulated pollutants that might have greater toxicity than larger particles, since they are more abundant and consequently have higher surface area per unit of mass. Our project aims to develop a relevant in vivo model of sub-chronic exposure to atmospheric particles in order to elucidate the specific respiratory impact of ultrafine particles compared to fine particulate matter. Quasi-ultrafine (PM0.18) and fine (PM2.5) particles have been collected in the urban industrial zone of Dunkirk in north France during a 7-month campaign, and submitted to physico-chemical characterization. BALB/c mice were then exposed intranasally to 10µg of PM0.18 or PM2.5 3 times a week. After 1 or 3-month exposure, broncho alveolar lavages (BAL) were performed and lung tissues were harvested for histological and transcriptomic analyses. The physico-chemical study of the collected particles shows that there is no major difference in elemental and surface chemical composition between PM0.18 and PM2.5. Furthermore, the results of the cytological analyses carried out show that both types of particulate fractions can be internalized in lung cells. However, the cell count in BAL and preliminary transcriptomic data suggest that PM0.18 could be more reactive and induce a stronger lung inflammation in exposed mice than PM2.5. Complementary studies are in progress to confirm these first data and to identify the metabolic pathways more specifically associated with the toxicity of ultrafine particles.

Keywords: environmental pollution, lung affect, mice, ultrafine particles

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Authors: Merfat Algethami, Anton Blencowe, Bryce Feltis, Stephen Best, Moshi Geso

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Nano-materials with high atomic number atoms have been demonstrated to enhance the effective radiation dose and thus potentially could improve therapeutic efficacy in radiotherapy. The optimal nanoparticulate agents require high X-ray absorption coefficients, low toxicity, and should be cost effective. The focus of our research is the development of a nanoparticle therapeutic agent that can be used in radiotherapy to provide optimal enhancement of the radiation effects on the target. In this study, we used bismuth (Bi) nanoparticles coated with starch and bismuth sulphide nanoparticles (Bi2S3) coated with polyvinylpyrrolidone (PVP). These NPs are of low toxicity and are one of the least expensive heavy metal-based nanoparticles. The aims of this study were to synthesise Bi2S3 and Bi NPs, and examine their cytotoxicity to human lung adenocarcinoma epithelial cells (A549). The dose enhancing effects of NPs on A549 cells were examined at both KV and MV energies. The preliminary results revealed that bismuth based nanoparticles show increased radio-sensitisation of cells, displaying dose enhancement with KV X-ray energies and to a lesser degree for the MV energies. We also observed that Bi NPs generated a greater dose enhancement effect than Bi2S3 NPs in irradiated A549 cells. The maximum Dose Enhancement Factor (DEF) was obtained at lower energy KV range when cells treated with Bi NPs (1.5) compared to the DEF of 1.2 when cells treated with Bi2S3NPs. Less radiation dose enhancement was observed when using high energy MV beam with higher DEF value of Bi NPs treatment (1.26) as compared to 1.06 DEF value with Bi2S3 NPs. The greater dose enhancement was achieved at KV energy range, due the effect of the photoelectric effect which is the dominant process of interaction of X-ray. The cytotoxic effect of Bi NPs on enhancing the X-ray dose was higher due to the higher amount of elemental Bismuth present in Bi NPs compared to Bi2S3 NPs. The results suggest that Bismuth based NPs can be considered as valuable dose enhancing agents when used in clinical applications.

Keywords: A549 lung cancer cells, Bi2S3 nanoparticles, dose enhancement effect, radio-sensitising agents

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Authors: Kailas L. Wasewar

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Biobutanol has been considered as a potential and alternative biofuel relative to the most popular biodiesel and bioethanol. End product toxicity is the major problems in commercialization of fermentation based process which can be reduce to some possible extent by removing biobutanol simultaneously. Several techniques have been investigated for removing butanol from fermentation broth such as stripping, adsorption, liquid–liquid extraction, pervaporation, and membrane solvent extraction. Liquid–liquid extraction can be performed with high selectivity and is possible to carry out inside the fermenter. Conventional solvents have few drawbacks including toxicity, loss of solvent, high cost etc. Hence alternative solvents must be explored for the same. Room temperature ionic liquids (RTILs) composed entirely of ions are liquid at room temperature having negligible vapor pressure, non-flammability, and tunable physiochemical properties for a particular application which term them as “designer solvents”. Ionic liquids (ILs) have recently gained much attention as alternatives for organic solvents in many processes. In particular, ILs have been used as alternative solvents for liquid–liquid extraction. Their negligible vapor pressure allows the extracted products to be separated from ILs by conventional low pressure distillation with the potential for saving energy. Morpholinium, imidazolium, ammonium, phosphonium etc. based ionic liquids have been employed for the separation biobutanol. In present chapter, basic concepts of ionic liquids and application in separation have been presented. Further, type of ionic liquids including, conventional, functionalized, polymeric, supported membrane, and other ionic liquids have been explored. Also the effect of various performance parameters on separation of biobutanol by ionic liquids have been discussed and compared for different cation and anion based ionic liquids. The typical methodology for investigation have been adopted such as contacting the equal amount of biobutanol and ionic liquids for a specific time say, 30 minutes to confirm the equilibrium. Further, biobutanol phase were analyzed using GC to know the concentration of biobutanol and material balance were used to find the concentration in ionic liquid.

Keywords: biobutanol, separation, ionic liquids, sustainability, biorefinery, waste biomass

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Authors: Adeyi Akindele Oluwatosin, Mustapha Kaosarat Keji, Ajisebiola Babafemi Siji, Adeyi Olubisi Esther, Damilohun Samuel Metibemu, Raphael Emuebie Okonji

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Envenoming by Echis ocellatus is potentially life-threatening due to severe hemorrhage, renal failure, and capillary leakage. These effects are attributed to snake venom metalloproteinases (SVMPs). Due to drawbacks in the use of antivenom, natural inhibitors from plants are of interest in studies of new antivenom treatment. Antagonizing effects of bioactive compounds of Moringa oleifera, a known antisnake plant, are yet to be tested against SVMPs of E. ocellatus (SVMP-EO). Ethanol crude extract of M. oleifera was partitioned using n-hexane and ethyl acetate. Each partition was fractionated using column chromatography and tested against SVMP-EO purified through ion-exchange chromatography with EchiTab-PLUS polyvalent anti-venom as control. Phytoconstituents of ethyl acetate fraction were screened against the catalytic site of crystal of BaP1-SVMP, while drug-likeness and ADMET toxicity of compound were equally determined. The molecular weight of isolated SVMP-EO was 43.28 kDa, with a specific activity of 245 U/ml, a percentage yield of 62.83 %, and a purification fold of 0.920. The Vmax and Km values are 2 mg/ml and 38.095 μmol/ml/min, respectively, while the optimal pH and temperature are 6.0 and 40°C, respectively. Polyvalent anti-venom, crude extract, and ethyl acetate fraction of M. oleifera exhibited a complete inhibitory effect against SVMP-EO activity. The inhibitions of the P-1 and P-II metalloprotease’s enzymes by the ethyl acetate fraction are largely due to methanol, 6, 8, 9-trimethyl-4-(2-phenylethyl)-3-oxabicyclo[3.3.1]non-6-en-1-yl)- and paroxypropione, respectively. Both compounds are potential drug candidates with little or no concern of toxicity, as revealed from the in-silico predictions. The inhibitory effects suggest that this compound might be a therapeutic candidate for further exploration for treatment of Ocellatus’ envenoming.

Keywords: Echis ocellatus, Moringa oleifera, anti-venom, metalloproteases, snakebite, molecular docking

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Authors: Hye-Hyun Lee, Hyo-Kon Chun, Kyung-Hee Kim Kim, Mi-Hee Kim, Saet-Byul Chu, Sang-Jong Lee, Seung-Hyeop Lee, Seung-Won Yi

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Some chemicals such as malachite green, methylene blue, and copper sulfate had been used frequently as disinfectants controlling fungal infection in aquaculture. However, their carcinogenicity, mutagenicity and teratogenicity were reported in mammals. After their accumulation in food fish and its consumers was confirmed, concerns about public health has resulted in enhanced monitoring and increased demand for eco-friendly treatments. Therefore, this study aimed to evaluate safety to fish and efficacy of sulfur solution processed by effective microorganisms (EM-PSS) against Saprolegnia parasitica, for use of a potential aquatic fungicidal disinfectant. The natural sulfur purchased from Kawah Ijen volcano, East Java, Indonesia was processed by the liquid mixture consisting of following twelve effective microorganisms (Rapha-el®; Lbiotech, Jeonnam, Korea), Lactobacillus parafarraginis, L. paracasei, L. harbinensis, L. buchneri, L. perolens, L. rhamnosus, L. vaccinostercus, Acetobacter lovaniensis, A. peroxydans, Pichia fermentans, Candida ethanolica, Saccharomycopsis schoenii isolated from fermentation process of oriental medicinal herbs including green tea, privet, and puer tea. The material was applied to in vitro antifungal activity test for Saprolegnia parasitica using agar dilution method. In addition, an acute toxicity test was performed on carp (Cyprinus carpio), eel (Anguilla japonica), and mud fish (Misgurnus mizolepis) for 96 hours. After three species of fish (n=15) were accustomed to experimental water environment for three days, the EM-PSS was added to each tank as final concentrations to be 0 to 500 ppm. The fish were taken into necropsy, and the histological sections of the gill, liver, and spleen were counter-stained with hematoxylin and eosin (H-E). And hence, no observed effect concentration (NOEC) of the solution was used for taking a medicinal bath for mudfish infected by Saprolegnia parasitica in practice. The result of in vitro antifungal activity test showed the growth inhibition of the fungus at 100 ppm, which and the lower concentrations occurred no fatal case in any fish species tested until the end of the examination. The 125 ppm of the solution, however, resulted in 13.3 %, 13.3 %, and 6.3 % of mortality in carp, eel, and mudfish, respectively. But both 250 and 500 ppm of the solution leaded lethality to all population of each fish species within 24 hours. Besides, H-E staining also showed no specific evidence for toxicity in fish at lesser than 100 ppm of EM-PSS. On the other hand, as a result of field application of the solution, no growth of fungal mycelium was found in fish bodies from gross observation 5 days post treatment. In conclusion, 100ppm of EM-PSS resulted in inhibition and treatment of Saprolegnia parasitica infection. In addition, the use of EM-PSS lower than 100 ppm is safe for fish. Therefore, EM-PSS could be used as aquatic fungicide, and also may be possible to be a potential eco-friendly disinfectant in aquaculture.

Keywords: antifungal activity, effective microorganism, toxicity, saprolegnia, processed sulfur solution

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

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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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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 Sn_0.5Ge_0.5I₃ 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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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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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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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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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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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)

Procedia PDF Downloads 85

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

Procedia PDF Downloads 338

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

Procedia PDF Downloads 201

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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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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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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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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