Diffusion of organochlorine (OCPs) and cypermethrin pesticides from rohu (Labeo rohita) internal organs to edible tissues during ice storage: a threat to human health.

The migration of organochlorine pesticides (OCPs) and cypermethrin residues from internal organs to edible tissues of ice-held Labeo rohita (rohu) was investigated in this study. The liver (246 µg/kg) had the highest level of ∑OCP residues, followed by the gills (226 µg/kg), intestine (167 µg/kg), and muscle tissue (54 µg/kg). The predominant OCPs in the liver and gut were endosulfan (53-66 µg/kg), endrin (45-53 µg/kg), and dichloro-diphenyl-trichloroethane (DDT; 26-35 µg/kg). The ∑OCP residues in muscle increased to 152 µg/kg when the entire rohu was stored in ice, but they decreased to 129 µg/kg in gill tissues. On days 5 and 9, the total OCPs in the liver increased to 317 µg/kg and 933 µg/kg, respectively. Beyond day 5 of storage, total internal organ disintegration had led to an abnormal increase in OCP residues of liver-like mass. Despite a threefold increase in overall OCP residues by day 9, accumulation of benzene hexachloride (BHC) and heptachlor was sixfold, endrin and DDT were fourfold, aldrin was threefold, and endosulfan and cypermethrin were both twofold. Endosulfan, DDT, endrin, and heptachlor were similarly lost in the gills at a rate of 40%, while aldrin and BHC were also lost at 60 and 30%, respectively. The accumulation of OCP residues in tissues has been attributed to particular types of fatty acid derivatives. The study concluded that while pesticide diffusion to edible tissues can occur during ice storage, the levels observed were well below the allowable limit for endosulfan, endrin, and DDT.

Influence of chlorpyrifos and endosulfan and their metabolites on the virulence of Helicobacter pylori.

Organochlorine (OC) and organophosphorus (OP) pesticides such as chlorpyrifos (CPF) and endosulfan (ES) have been associated with a plethora of adverse health effects. Helicobacter pylori (H. pylori) infection can lead to gastrointestinal diseases by regulating several cellular processes. Thus, the current study focuses on the effect of the co-exposure to pesticides and H. pylori on gastric epithelial cells. We have used the in-silico approach to determine the interactive potential of pesticides and their metabolites with H. pylori-associated proteins. Further, various in-vitro methods depict the potential of ES in enhancing the virulence of H. pylori. Our results showed that ES along with H. pylori affects the mitochondrial dynamics, increases the transcript expression of mitochondrial fission genes, and lowers the mitochondrial membrane potential and biomass. They also promote inflammation and lower oxidative stress as predicted by ROS levels. Furthermore, co-exposure induces the multi-nucleated cells in gastric epithelial cells. In addition, ES along with H. pylori infection follows the extrinsic pathway for apoptotic signaling. H. pylori leads to the NF-κB activation which in turn advances the ß-catenin expression. The expression was further enhanced in the co-exposure condition and even more prominent in co-exposure with ES-conditioned media. Thus, our study demonstrated that pesticide and their metabolites enhance the pathogenicity of H. pylori infection.

Endosulfan affects embryonic development synergistically under elevated ambient temperature.

In the present study, we determined the developmental toxicity of endosulfan at an elevated ambient temperature using the zebrafish animal model. Zebrafish embryos of various developmental stages were exposed to endosulfan through E3 medium, raised under two selected temperature conditions (28.5 °C and an elevated temperature of 35 °C), and monitored under the microscope. Zebrafish embryos of very early developmental stages (cellular cleavage stages, such as the 64-cell stage) were highly sensitive to the elevated temperature as 37.5% died and 47.5% developed into amorphous type, while only 15.0% of embryos developed as normal embryos without malformation. Zebrafish embryos that were exposed concurrently to endosulfan and an elevated temperature showed stronger developmental defects (arrested epiboly progress, shortened body length, curved trunk) compared to the embryos exposed to either endosulfan or an elevated temperature. The brain structure of the embryos that concurrently were exposed to the elevated temperature and endosulfan was either incompletely developed or malformed. Furthermore, the stress-implicated genes hsp70, p16, and smp30 regulations were synergistically affected by endosulfan treatment under the elevated thermal condition. Overall, the elevated ambient temperature synergistically enhanced the developmental toxicity of endosulfan in zebrafish embryos.

Remediation of endosulfan-contaminated water by hairy roots: removal and phytometabolization assessment.

Although many countries banned the insecticide endosulfan, it is still an environmental pollutant. Plants metabolize the two diastereomers of the formulations known as technical grade endosulfan (TGE) by two phase I pathways: hydrolysis leading to less toxic derivatives and oxidation giving endosulfan sulfate which is as toxic as endosulfan itself. We assessed the removal, bioaccumulation and phase I metabolization of TGE from water matrices using hairy root clones (HRs) of three edible species, Brassica napus, Raphanus sativus and Capsicum annuum. B. napus and C. annuum HRs removed 86% of TGE from the bioreaction media in 2 and 96 h, respectively, whereas R. sativus HRs removed 91% of TGE within 6 h of biotreatment. In the experiments with B. napus, only endosulfan sulfate was detected in both biomass and medium, whereas R. sativus and C. annuum accumulated endosulfan sulfate and endosulfan alcohol. Besides, endosulfan lactone was detected in C. annuum reaction medium. Acute ichthyotoxicity assays toward Poecilia reticulata showed that media contaminated with TGE lethal levels did not produce mortality after the phytotreatments. This research highlights the feasibility of using HRs to evaluate plant enzymatic abilities toward xenobiotics and their potential for the design of ex situ decontamination processes.

Endosulfan induced kidney cell injury by modulating ACE2 through up-regulating miR-429 in HK-2 cells.

Endosulfan, a typical organochlorine pesticide, is widely used in agricultural countries and was detected in blood samples from the general population. Studies have shown a positive correlation between chronic kidney disease of unknown aetiology (CKDu) and endosulfan. CKDu has become endemic in agricultural countries, with clinical manifestations of tubulointerstitial fibrosis.The goal of this study was to investigate the effects of endosulfan in kidney cell injury in human renal tubular epithelial cells (HK-2), focusing on apoptosis, inflammatory response, and epithelial-mesenchymal transition (EMT). We found that endosulfan induced apoptosis in HK-2 cells by up-regulating the expression of BAX, APAF-1, Caspase-3 and mitochondrial Cytochrome c was released into the cytosol. Endosulfan caused an inflammatory response, showing the increase in the secretion and mRNA expression levels of IL-6/IL-8. Endosulfan triggered EMT, characterized by downregulation of E-cadherin and upregulation of Vimentin. Western blot results showed that p-Smad3 and Smad3 protein expression were elevated while the expression of Smad7 were decreased in endosulfan-exposed groups. Dual luciferase reporter assay confirmed the potential binding capacity of miR-429 to 3'-UTR of ACE2. Endosulfan causes upregulation of miR-429 and downregulation of ACE2 in HK-2 cells. Overexpression of miR-429 or silencing of ACE2 in HK-2 cells caused apoptosis, inflammation and EMT through TGF signaling pathway. These findings suggest that endosulfan can lead to kidney cell injury by modulating ACE2 through up-regulating miR-429, providing new evidence for the pathogenesis of CKDu.

Possible mechanisms involved in the testicular-protective property of quercetin in rats exposed to endosulfan toxicity.

The study investigated the effects of quercetin and putative mechanisms involved against endosulfan-testicular impairments in rats. Rats were allotted into five treatment groups (n = 5). Groups 1-2 had normal saline and maize oil (vehicle) (10 mL/kg), group 3 received quercetin (20 mg/kg), 4-5 had endosulfan (5 mg/kg, p.o) orally for 28 days. However, from days 14-28, group 4 received an additional dose of vehicle (10 mL/kg, p.o./day), while group 5 received quercetin (20 mg/kg, p.o./day). Thereafter, blood samples and testes were harvested for markers of cholinergic, hormonal and testicular oxido-nitrergic, inflammatory, apoptosis and proton pump ATPase activities. Also, testicular histopathological changes were also evaluated alongside with germ cell count, testicular injury and spermatogenesis score. Quercetin increased testicular/body weights and spermatogenesis, androgenic hormones (follicle stimulating hormones, FSH; luteinizing hormone, LH; testosterone), acetylcholinesterase levels and attenuated altered membrane integrity, DNA fragmentation, increased caspases-3 levels in rats exposed to endosulfan. Moreover, quercetin increased testicular B-cell lymphoma-2 (Bcl-2), Bcl-2 associated x-protein (Bax) and proton pump adenosine trisphosphate (ATPase) and sialic acid levels. Of note, quercetin reversed endosulfan-mediated increased malondialdehyde, nitrite, peroxynitrite formation, 8-hydroxy-2'-deoxyguanosine and lowered antioxidant enzymes in the testes. The increased levels of testicular myeloperoxidase (MPO), tumor necrosis factor-alpha (TNF-α) and interleukin-1beta (IL-1ß) by endosulfan were also reduced by quercetin administration. Additionally, quercetin attenuate endosulfan-induced testicular histopathological changes of rats. Our findings showed that quercetin significantly inhibited endosulfan-induced testicular damage and altered spermatogenesis through inhibition of oxido-nitrergic pathway, inflammatory mediators, apoptosis, acetylcholinesterase activity and enhancement of testicular hormones and improvement in testicular ATPase activity.

Whole-Genome Sequencing Reveals Germ Cell Mutagenicity of α-Endosulfan in Caenorhabditis elegans.

Endosulfan is an extensively used organochlorine pesticide around the world, which was classified as a persistent organic pollutant (POP) in 2009. Although previous studies have documented the reproductive toxicity of endosulfan in a variety of organisms, little is known about the influence of endosulfan on the genome stability of germ cells and nonexposed progeny. Here we applied whole-genome sequencing to explore the germ cell mutagenicity of α-endosulfan in Caenorhabditis elegans (C. elegans). We found that, although low doses of α-endosulfan exhibited a minor effect on the reproductive capacity of C. elegans, chronic exposure to 1 µM α-endosulfan significantly increased the mutation frequencies of nonexposed progeny. Further analysis of genome-wide mutation spectra demonstrated that α-endosulfan preferentially elicited A:T → G:C substitutions and clustered mutations. By using worms deficient in DNA damage response genes, our results suggest the involvement of translesion synthesis polymerase η in modulating α-endosulfan-induced mutations in germ cells. Together, these observations reveal the germ cell mutagenicity of α-endosulfan in C. elegans and the possible underlying mechanism. In addition, our findings implicate that germ cell mutagenicity might be a necessary consideration for the health risk assessment of environmental chemicals such as POPs.

Organochlorine pesticides induce epithelial as well as inflammatory mediators following exposure to human ovarian surface epithelial cells: An in vitro study.

Although studies have suggested organochlorine pesticides (OCPs) exposure increased the risk of epithelial ovarian cancer, the mechanisms underlying its potential tumorigenic effects in the human ovary are not well understood. In this study, we investigated the impact of dichlorodiphenyldichloroethylene (DDE), endosulfan, and heptachlor exposure on epithelial cadherin (E-cadherin) and proinflammatory mediators in human ovary surface epithelial (HOSE) cells. We found that DDE, endosulfan, and heptachlor exposure resulted in epithelial differentiation accompanied by upregulation of E-cadherin expression and overexpression of proinflammatory cytokines (TNFα, IL-1ß, and IL-6) in HOSE cells. The epithelial differentiation may accelerate HOSE cells to inclusion body formation, a common site for ovarian cancer initiation and persistent exposure to OCPs creates a chronic inflammatory microenvironment that may promote the neoplastic transformation of HOSE cells within the inclusion cyst.

Effects of the insecticide ß-endosulfan on tadpoles of Isthmohyla pseudopuma (Anura: Hylidae).

Conventional agriculture uses pesticides intensively. Once pesticides are released into the environment, they can be toxic to non-target organisms. Exposure of amphibians to pesticides can be lethal and affect their growth, development and behavior. ß-endosulfan is a persistent organochlorine that has been detected in environmental samples within protected sites in Costa Rica, far from agricultural areas. The aim of this study was to evaluate the lethal and sublethal effects, as well as changes in three biomarkers (Cholinesterase activity [ChE], glutathione S-transferase activity [GST] and lipid peroxidation [LPO]) in tadpoles of Isthmohyla pseudopuma exposed to ß-endosulfan. A 96-h acute test (20, 40, 60, 80, 100 and 200 µg/L) was performed in order to calculate the median lethal concentration (LC50), while effects on growth and development were assessed during a 4-weeks chronic test (10, 20, 30 and 50 µg/L). In addition, we measured the aforementioned biomarkers in tadpoles exposed to concentrations below the LC50. The 96-h LC50 for this species was 123.6 µg/L. We found no evidence of ß-endosulfan influencing any of the three biomarkers evaluated. At 50 µg/L, both length and total weight of tadpoles decreased with respect to the control. Also, at 30 and 50 µg/L we observed that individuals showed a slower development. Therefore, we demonstrated that at sublethal concentrations, ß-endosulfan negatively affects I. pseudopuma at early stages causing tadpoles to develop slower and smaller than normal.

The effects of endosulfan on cell migration and invasion in prostate cancer cells via the KCNQ1OT1/miR-137-3p/PTP4A3 axis.

Endosulfan belongs to persistent organic pollutants (POPs), closely related to an increased risk of prostate cancer (PCa). The existing evidence shows that lncRNAs compete with miRNAs for binding sites and contribute to the onset and progression of human malignancies. In this study we investigate how endosulfan promotes cell migration and invasion in DU145 and PC3 prostate cancer cells through epigenetic mechanism of lncRNA-miRNA regulation. Based on our past research we focused on PTP4A3 and constructed wild-type (WT) and mutant PTP4A3 plasmids for further analysis. Our results revealed that transfection of PTP4A3-WT can lead to changes in the expression of epithelial-mesenchymal transition (EMT) biomarkers and critical proteins in the TGF-ß signaling pathway, and promote cell migration and invasion in PCa cells. Bioinformatics analysis shows that there were complementary sequences in PTP4A3 3'-UTR and KCNQ1OT1 3'-UTR to the seed sequence of hsa-miR-137-3p, and dual luciferase reporter assay indicates the potential binding capacity of miR-137-3p to 3'-UTR of PTP4A3 and KCNQ1OT1. We found that miR-137-3p mimic inhibited cell migration and invasion, as well as repressed alterations of EMT biomarkers and critical proteins in the TGF-ß signaling pathway. Rescue experiment results revealed that co-transfection of miR-137-3p mimic and PTP4A3-WT plasmid reversed these changes following transfection with miR-137-3p mimic alone. We found that KCNQ1OT1 was predominantly distributed in the cytoplasm from a subcellular fractionation assay. Functionally, silencing of KCNQ1OT1 repressed cell migration and invasion, and caused alterations of EMT biomarkers and critical proteins in the TGF-ß signaling pathway, which were all restored by co-transfection with anti-miR-137-3p or PTP4A3-WT plasmid. Furthermore, overexpression of miR-137-3p or silencing of KCNQ1OT1 dramatically rescued the effects of endosulfan on promoting cell migration and invasion. These findings suggest that endosulfan can indeed promote cell migration and invasion via the KCNQ1OT1/miR-137-3p/PTP4A3 axis in PCa cells.

Endosulfan causes oxidative stress in the liver and brain that involves inhibition of NADH dehydrogenase and altered antioxidant enzyme status in rat.

Endosulfan, a neurotoxic, highly persistent organochlorine insecticide, is known for its acute and chronic toxicity. We have shown that a single sublethal dose of endosulfan caused high induction of oxidative stress in the liver and brain by altering the antioxidant status, as shown by reduction in the antioxidant enzymes SOD, GPx, GST, GR along with increased ROS and lipid peroxidation. The cerebral region in the brain showed a higher level of oxidative stress than the cerebellum, revealing differential sensitivity of the brain regions to endosulfan. Depletion of natural antioxidants causes the imbalance of redox status in cells, and the role of mitochondrial distress causally related to the cellular oxidative stress in vivo is not well understood. We have shown that reduction in the mitochondrial NADH dehydrogenase activity in the brain is associated with the induction of ROS in endosulfan-treated rats. Although oxidative stress is induced in both the liver and brain, the oxidative damage to the brain has implications for the toxic outcome in view of the brain's lower antioxidant defenses and high oxygen consumption.

Aberrant Hoxa10 gene methylation as a mechanism for endosulfan-induced implantation failures in rats.

DNA methylation is a well-established epigenetic mechanism controlling gene expression. Environmental chemicals, such as pesticides have been shown to alter DNA methylation. We have previously shown that the insecticide endosulfan impairs female fertility in rats by increasing the rate of preimplantation embryo losses. In this study, we evaluated whether early postnatal exposure to endosulfan affects long-term transcriptional regulation of Homeobox A10 (Hoxa10) gene, which is a key marker of endometrial receptivity. Female rats were neonatally exposed to 6 or 600 µg/kg/day (ENDO6 and ENDO600, respectively) of endosulfan and uterine samples collected on gestational day (GD) 5. Hoxa10 protein and mRNA levels were assessed by immunohistochemistry and quantitative real-time PCR (qRT-PCR), respectively. In silico analysis of enzyme-specific restriction sites and predicted transcription factors were performed to investigate the methylation status of the regulatory regions of Hoxa10 gene by methylation-sensitive restriction enzymes-PCR technique. The expression of the DNA methyltransferases (Dnmts) was also evaluated. ENDO600 showed a decreased uterine Hoxa10 expression at protein and transcript level, while ENDO6 decreased only the level of transcripts, during the receptive stage. In addition, endosulfan increased levels of Dnmt3a and Dnmt3b. Dysregulation of DNA methylation patterns of Hoxa10 regulatory regions was detected in ENDO6- and ENDO600-treated rats. All these results suggest that aberrant DNA methylation in Hoxa10 gene could be an underlining mechanism contributing to explain endosulfan-induced preimplantation losses.

Concentrations, distribution, and risk assessment of endosulfan residues in the cotton fields of northern Xinjiang, China.

In the current study, surface soil samples were collected from cotton fields in Shawan and Shihezi areas in northern Xinjiang and tested for endosulfan residues using gas chromatography-mass spectrometry. Results showed endosulfan sulfate was the predominant compound in the surface soil studied, followed by ß-endosulfan and α-endosulfan with detection rates of 86.9%, 55.7%, and 49.2%, respectively, for the 61 soil samples collected. The average concentrations of endosulfan sulfate, α-endosulfan, and ß-endosulfan were 0.743, 0.166, and 0.073 µg/kg, respectively. The ratios of α-/ß-endosulfan were below 2.33 in all samples tested, suggesting no new endosulfan was added to the soil and the presence of endosulfan residues in this region was due to historical application in the past. According to the health risk assessment model recommended by the USA Environmental Protection Agency, the health risk of endosulfan residues in the studied area was low, and the maximum values of noncarcinogenic risks for children and adults were 2.30 × 10-5 and 2.70 × 10-6, respectively. Folsomia candida was the most sensitive organism to total endosulfan residues, with 38% of the total sampling sites classified as high risk. For earthworms, the proportion of high risk site was 13%. Lactuca sativa was the most tolerant organism to ∑ESs, with all sampling sites identified as negligible risk. This study provided current status of endosulfan residues and related risk in cotton fields, which could be used to support decision makers to prepare relevant regulations.

Toxicological assessment of low-dose bisphenol A, lead and endosulfan combination: chronic toxicity study in male rats.

In the present study, toxic effects, both alone and combined, of bisphenol A (BPA), lead (Pb) and endosulfan (ES) in the low doses were investigated in rat liver and kidney functions. In the study, bisphenol A (BPA), lead (Pb) and endosulfan (ES) were chosen because although they are the chemicals people are most frequently exposed to, no combined toxic effect studies were conducted with these chemicals. Sixty-four male Wistar albino rats were used in the study, and they were randomly divided into eight groups (n = 8 per group); control, BPA (5 mg/kg), Pb (100 ppm), ES (0.61 mg/kg), BPA+Pb, BPA+ES, Pb+ES and BPA+P+ES. The rats were sacrificed after 65 days of treatment. Severe histopathological changes in the liver and kidney tissues were observed in the rats exposed to BPA+Pb+ES combination. Elevated malondialdehyde (MDA) in the liver and decreased superoxide dismutase activity (SOD) in the kidney tissue were detected in the BPA+Pb+ES group compared to those of the control group. It was found that serum alanine aminotransferase (ALT) and blood urea nitrogen (BUN) and creatinine (CREA) levels were higher in the BPA+Pb+ES combination group than the control group. Also, combined exposure of BPA, Pb and ES caused apoptotic cell numbers and inducible nitric oxide (iNOS) to increase in the liver and kidney tissues. The results of the present study suggested that the BPA, Pb and ES caused more dramatic changes to both histological architecture and cell apoptosis in the liver and kidney tissues when there was a combined exposure.

Mycoremediation of an agricultural salty soil contaminated with endosulfan by Penicillium crustosum: and agronomic bioassays with Phaseolus leptostachyus.

The fungus Penicillium crustosum was employed for endosulfan biodegradation, finding that sulphate endosulfan and mono alcohol endosulfan were the main compounds produced; therefore, an oxidative degradation pathway was suggested. A 93 ± 4.7% of Endosulfan degradation after one month of treatment of a highly salty agricultural soil was obtained, where ΔST was up to 17 ± 0.58 mN m-1, (related to the water value of 72 mNm-1), that was induced by the fungus during soil mycoremediation Additionally, an improvement in soil quality (reduction of clay proportion and salinity, as well as an increase of soluble phosphorus, carbon content and organic matter) was observed during the mycoremediation treatment. The phytotoxicity of the pesticide on Phaseolus leptostachyus was evaluated in the soil without the fungus addition (control), where the pesticide was translocated in the crop, presenting a negative effect in germination index, root length and weight, aerial weight, humidity, and proline content. This contrasted with the effect on the crop grown in the soil treated with P. crustosum, which had better agronomic characteristics. This is first report in which the effect of this property allows the pesticide biodegradation, due to a combined Endosulfan bioavailability and fungal biodegradation.

ß-Endosulfan-mediated induction of pro-fibrotic markers in renal (HK-2) cells in vitro: A new insight in the pathogenesis of chronic kidney disease of unknown etiology.

Chronic kidney disease of unknown etiology (CKDu), manifested clinically as tubulo interstitial fibrosis, has emerged as the second major cause of chronic kidney disease (CKD) in the Indian subcontinent and various agrochemicals have been implicated in its occurance. Among the agrochemicals organochlorine pesticides particularly endosulfan is well known for its toxicity and recent residue analysis have shown its presence in the blood samples of general population. In this present study, we have investigated the consequences of endosulfan exposure at a concentration (0.01 µM) equivalent to their highest reported presence in human blood sample of some CKDu patients, to human renal proximal tubular epithelial (HK-2) cell line with regard to ROS generation and expression of profibrotic and epithelial to mesenchymal (EMT) markers in order to find out endosulfan's ability to induce profibrotic changes in renal cell. We demonstrated a significant increase in intracellular ROS generation and increased expression of TGF-ß1 when cells were incubated with ß-endosulfan (0.01 µM) indicating occurrence of oxidative stress and fibrotic process. Again, decreased expression of epithelial marker E-cadherin and increase in the expression of mesenchymal marker α-smooth muscle actin (α-SMA) suggest possible onset of EMT process. Pre-treatment with 5 mM concentration of anti-oxidant N-acetyl cysteine partially attenuated the above process. In conclusion, these findings suggest possible involvement of ß-endosulfan in the development of CKDu through oxidative stress and profibrotic signaling.

Repeated endosulfan exposure induces changes in neurochemicals, decreases ATPase transmembrane ionic-pumps, and increased oxidative/nitrosative stress in the brains of rats: Reversal by quercetin.

Neurochemical and ATPase deregulations play important role in toxicant-induced neurodegeneration. Previous studies have shown that loss of ATPase ionic-pumps alters neurochemical balance via increased ammonia, oxidative and nitrosative stress. Thus, this study investigated the ameliorative potentials of quercetin on neurochemical, ATPase changes, hyperammonemia and oxidative/nitrosative status in the brains of Wistar rats exposed to endosulfan, a known toxic environmental pesticide that is casually used in many developing countries. Adult rats were divided into five treatment groups (n = 5). Groups 1-2 received normal saline and corn oil (vehicle) (10 mL/kg/day), group 3 received quercetin (20 mg/kg/day) orally for 28 days consecutively. However, animals in groups 4-5 were given endosulfan (5 mg/kg/day, p.o) for 28 days. But, from the 14th to 28th day, group 4 additionally received vehicle (10 mL/kg/day, p.o.), while group 5 was treated with quercetin (20 mg/kg/day, p.o.). Thereafter, brain levels of neurochemicals, ATPase activities, ammonia and oxidative/nitrosative stress were investigated by employing standardized biochemical assay protocols. Quercetin increased endosulfan-induced decreased levels of norepinephrine, dopamine, GABA, and decreased elevated concentrations of glutamate and serotonin. Quercetin normalized the increased levels of acetylcholinesterase and ammonia. Furthermore, quercetin significantly reversed the decrease in Na+/K+, Ca2+, Mg2+-ATPase activities induced by endosulfan. Also, quercetin increased superoxide dismutase, catalase and glutathione peroxidase activities, and reduced nitrite and peroxynitrite levels in brains of rats. These findings further provide evidence of the ameliorative potential of quercetin against endosulfan-induced neurotoxicity via attenuation of neurochemical, ATPase changes, and inhibition of acetylcholinesterase activity, ammonia release and oxidative/nitrosative stress in rat brains.

Persistent pesticides: effects of endosulfan at the molecular level on the aquatic invertebrate Chironomus riparius.

Although banned in multiple areas, due to its persistence in the environment, endosulfan constitutes a significant environmental concern. In this work, fourth instar Chironomus riparius larvae were exposed at environmentally relevant endosulfan concentrations of 0.1, 1, and 10 µg/L for 24 h to analyze the possible effects of this acaricide on gene expression and enzymatic activity. Transcriptional changes were studied through the implementation of a real-time polymerase chain reaction array with 42 genes related to several metabolic pathways (endocrine system, detoxification response, stress response, DNA reparation, and immune system). Moreover, glutathione-S-transferase (GST), phenoloxidase (PO), and acetylcholinesterase (AChE) activities were assessed. The five pathways were differentially altered by endosulfan exposure with significant changes in the E93, Dis, MAPR, Met, InR, GSTd3, GSTt3, MRP1, hsp70, hsp40, hsp24, ATM, PARP, Proph, and Def genes. Besides, all of the measured enzymatic activities were modified, with increased activity of GST, followed by PO and AChE. In summary, the results reflected the effects provoked in C. riparius at molecular level despite the absence of lethality. These data raise concerns about the strong alteration on different metabolic routes despite the low concentrations used. Therefore, new risk assessment strategies should consider include the effects at the sub-organismal level as endpoints in addition to the classical ecologically relevant parameters (such as survival). This endeavor will facilitate a comprehensive evaluation of toxicants in the environment.

Assessment of DNA damage induced by endosulfan in grass carp (Ctenopharyngodon idella Valenciennes, 1844).

Endosulfan is an organochlorine pesticide, which is commonly used throughout the world. It accumulates in the environment and may cause significant damage to the ecosystems, particularly to the aquatic environments. The present study was conducted to evaluate the genotoxic effect of endosulfan on the grass carp (Ctenopharyngodon idella) blood. The fish were exposed to three different concentrations, 0.75 ppb/day, 1.0 ppb/day, and 1.5ppb/day of endosulfan for 7, 14, 21, and 28 days. The study was a randomized control trial and the control group was not exposed to endosulfan. The results showed that after 7 days, the level of DNA damage in all the concentrations was significant (P < 0.05), while after 14, 21, and 28 days' trials, highly significant (P < 0.000) level of DNA damage was observed. Hence, time- and dose-dependent DNA damage was observed in fish DNA by comet assay. It is concluded from our results that with the increase in endosulfan concentration and exposure duration, the level of DNA damage also increased. As the current study showed the severe genotoxic effect of endosulfan in Ctenopharyngodon idella, therefore, the imprudent and indiscriminate use of endosulfan should be controlled and monitored by the concerned government authorities.

Fluoride and endosulfan together potentiate cytogenetic effects in Swiss albino mice bone marrow cells.

In this study, the cytotoxic potential of fluoride and endosulfan in combination was investigated in Swiss albino mice bone marrow cells using the chromosomal aberration (CA) and micronucleus (MN) test systems. Fluoride (25.1 mg kg-1 body weight [bw] in water) and endosulfan (1.8 mg kg-1 bw by oral intubation) were administered orally alone and in combination (fluoride 25.1 mg kg-1 bw + endosulfan 1.8 mg kg-1 bw) to male Swiss albino mice daily for 30 days. A significant (p < 0.01) increase in micronuclei (MNs) induction and decreased ratio (p < 0.01) of polychromatic to normonochromatic erythrocytes (indicators of cytotoxicity) were observed compared with saline controls when animals were given the combination of fluoride and endosulfan. A significant (p < 0.01) increase in MNs induction and no change in the polychromatic erythrocytes to erythrocyte ratio were also observed when endosulfan was given alone. CAs such as gaps, breaks, fragments, rings, exchanges, and polyploidy were recorded in the bone marrow cells. The mean percent frequency of CAs was increased (p < 0.01) in all the treated groups compared with the control saline group. In the combination group (F + E), the percent frequencies of CAs were significantly higher (13.875%) compared with those in the individual treatment groups of fluoride (4.375%) and endosulfan (6.25%). The mitotic index was calculated as percentage of dividing cells. A significant (p < 0.01) decrease in mitotic index was observed in all treated groups compared with controls. In the combination group (F + E), mitotic index was significantly less than (p < 0.01; 4.1 ± 0.49) the saline control (10.8 ± 0.98). These results indicated that repeated intake of endosulfan through various sources in fluoride affected areas resulted in increased cytotoxic effects. The greater effect in the combination group indicated additive interaction of fluoride and endosulfan in inducing cytotoxicity in Swiss albino mice.