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Kiran Dip Gill - One of the best experts on this subject based on the ideXlab platform.
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Dichlorvos exposure results in activation induced apoptotic cell death in primary rat microglia
Chemical Research in Toxicology, 2012Co-Authors: Aditya Sunkaria, Willayat Yousuf Wani, Deep Raj Sharma, Kiran Dip GillAbstract:Dichlorvos [2,2-dichlorovinyl dimethyl phosphate] is one of the most common in-use organophosphate (OP) in developing nations. Previous studies from our lab have shown chronic Dichlorvos exposure leads to neuronal cell death in rats. However, the extent of damage caused by Dichlorvos to other cells of the central nervous system (CNS) is still not clear. Microglial cells are the primary threat sensors of CNS which become activated in many pathological conditions. Activation of microglial cells results in reactive microgliosis, manifested by increased cellular damage in the affected regions. Using rat primary microglial cultures, here we show that Dichlorvos exposure can activate and induce apoptotic cell death in microglia. We observed significant up-regulation of pro-inflammatory molecules like nitric oxide, TNF-α, and IL-1β when microglia were treated with Dichlorvos (10 μM). Significant up-regulation of CD11b, microglial specific activation marker, was also observed after 24 h of Dichlorvos treatment. The activated microglial cells eventually undergo cell death after 48 h of Dichlorvos treatment. The DNA fragmentation pattern of Dichlorvos treated microglia along with increased expression of Bax in mitochondria, cytochrome c release from mitochondria, and caspase-3 activation led us to assume that microglia were undergoing apoptosis. Thus, the present study showed that Dichlorvos can induce microglial activation and ultimately apoptotic cell death. These findings gave new perspective to the current knowledge of Dichlorvos (OPs) mediated CNS damage and presents microglial activation as a potential therapeutic target for preventing the OP induced neuronal damage.
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protective efficacy of mitochondrial targeted antioxidant mitoq against Dichlorvos induced oxidative stress and cell death in rat brain
Neuropharmacology, 2011Co-Authors: Willayat Yousuf Wani, Satish Gudup, Aditya Sunkaria, Parvinder Pal Singh, Deep Raj Sharma, Ramesh Kandimalla, Kiran Dip GillAbstract:Abstract Dichlorvos is a synthetic insecticide that belongs to the family of chemically related organophosphate (OP) pesticides. It can be released into the environment as a major degradation product of other OPs, such as trichlorfon, naled, and metrifonate. Dichlorvos exerts its toxic effects in humans and animals by inhibiting neural acetylcholinesterase. Chronic low-level exposure to Dichlorvos has been shown to result in inhibition of the mitochondrial complex I and cytochrome oxidase in rat brain, resulting in generation of reactive oxygen species (ROS). Enhanced ROS production leads to disruption of cellular antioxidant defense systems and release of cytochrome c (cyt c) from mitochondria to cytosol resulting in apoptotic cell death. MitoQ is an antioxidant, selectively targeted to mitochondria and protects it from oxidative damage and has been shown to decrease mitochondrial damage in various animal models of oxidative stress. We hypothesized that if oxidative damage to mitochondria does play a significant role in Dichlorvos induced neurodegeneration, then MitoQ should ameliorate neuronal apoptosis. Administration of MitoQ (100 μmol/kg body wt/day) reduced Dichlorvos (6 mg/kg body wt/day) induced oxidative stress (decreased ROS production, increased MnSOD activity and glutathione levels) with decreased lipid peroxidation, protein and DNA oxidation. In addition, MitoQ also suppressed DNA fragmentation, cyt c release and caspase-3 activity in Dichlorvos treated rats compared to the control group. Further electron microscopic studies revealed that MitoQ attenuates Dichlorvos induced mitochondrial swelling, loss of cristae and chromatin condensation. These results indicate that MitoQ may be beneficial against OP (Dichlorvos) induced neurodegeneration.
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cellular and molecular mechanisms of Dichlorvos neurotoxicity cholinergic nonchlolinergic cell signaling gene expression and therapeutic aspects
Indian Journal of Experimental Biology, 2010Co-Authors: B K Binukumar, Kiran Dip GillAbstract:Inappropriate use of toxic chemicals is common in developing countries, where it leads to excessive exposure and high risks of unintentional poisoning. Risks are particularly high with the pesticides used in agriculture, poor rural populations live and work in close proximity to these compounds and often store these compounds in and around their homes. It is estimated that most of the death from pesticide poisoning occur in developing countries. Organophosphate insecticides have been extensively used in agriculture in developing countries. Dichlorvos is a synthetic insecticide and belongs to a family of chemically related organophosphate pesticides (OP). Toxicity of Dichlorvos has been documented in accidental human poisoning, epidemiological studies, and animal models. In this review, molecular mechanisms of Dichlorvos neurotoxicity have been described. Usage, biotransformation, environmental levels, general population and occupational exposure, effects on cell signaling receptors, mitochondrial metabolism, oxidative stress and gene expression of Dichlorvos have been reviewed. Assessment of acute and chronic exposures as well as neurotoxicity risk for lifetime exposures to Dichlorvos have also been considered. In addition special emphasis has been given to describe, the role of Dichlorvos in the chronic neurotoxicity and its molecular targets that ultimately lead to neurodegeneration.
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impaired mitochondrial energy metabolism and neuronal apoptotic cell death after chronic Dichlorvos op exposure in rat brain
Neurotoxicology, 2007Co-Authors: Pushpinder Kaur, Bishan D Radotra, Ranjana W Minz, Kiran Dip GillAbstract:Abstract The present study elucidates a possible mechanism by which chronic organophosphate exposure (Dichlorvos 6 mg/kg bw, s.c. for 12 weeks) causes neuronal degeneration. Mitochondria, as a primary site of cellular energy generation and oxygen consumption represent itself a likely target for organophosphate poisoning. Therefore, the objective of the current study was planned with an aim to investigate the effect of chronic Dichlorvos exposure on mitochondrial calcium uptake, oxidative stress generation and its implication in the induction of neuronal apoptosis in rodent model. Mitochondrial preparation from Dichlorvos (DDVP) treated rat brain demonstrated significant increase in mitochondrial Ca 2+ uptake (644.2 nmol/mg protein). Our results indicated decreased mitochondrial electron transfer activities of cytochrome oxidase (complex IV) along with altered mitochondrial complex I, and complex II activity, which might have resulted from elevated mitochondrial calcium uptake. The alterations in the mitochondrial calcium uptake and mitochondrial electron transfer enzyme activities in turn might have caused an increase in malondialdehyde, protein carbonyl and 8-hydoxydeoxyguanosine formation as a result of enhanced lipid peroxidation, and as well as protein and mtDNA oxidation. All this could have been because of enhanced oxidative stress, decreased GSH levels and also decreased Mn-SOD activity in the mitochondria isolated from Dichlorvos treated rat brain. Thus, chronic organophosphate exposure has the potential to disrupt cellular antioxidant defense system which in turn triggers the release of cytochrome c from mitochondria to cytosol as well as caspase-3 activation in Dichlorvos treated rat brain as revealed by immunoblotting experiments. Low-level long-term organophosphate exposure finally resulted in oligonucleosomal DNA fragmentation, a hallmark of apoptosis. These studies provide an evidence of impaired mitochondrial bioenergetics and apoptotic neuronal degeneration after chronic low-level exposure to Dichlorvos.
Debapratim Kar Chowdhuri - One of the best experts on this subject based on the ideXlab platform.
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adverse effect of organophosphate compounds Dichlorvos and chlorpyrifos in the reproductive tissues of transgenic drosophila melanogaster 70 kda heat shock protein as a marker of cellular damage
Toxicology, 2007Co-Authors: Subash C Gupta, Hifzur R Siddique, D K Saxena, Neeraj Mathur, Ranjit K Mishra, Debapratim Kar ChowdhuriAbstract:Abstract The study highlights the adverse effects of organophosphate compounds Dichlorvos and chlorpyrifos on reproduction in Drosophila . Freshly eclosed first instar larvae of Drosophila melanogaster transgenic for hsp70 ( hsp70 - lacZ ) Bg 9 were fed on 0.015–150.0 ppb Dichlorvos and chlorpyrifos mixed food. Virgin flies eclosing from the normal and contaminated food were pair-mated to examine the effect of the test chemicals on reproduction of the exposed organisms. Expression of hsp70 , sex peptide (SP or Acp70A), accessory gland protein (Acp36DE) and tissue damage was examined in reproductive organs of adult fly. Exposed organisms exhibited a dose-dependent significantly reduced reproductive outcome and males were found to be more sensitive than females. Hsp70 expression was restricted only within the testis lobes of male fly while it was not induced in the ovary of the female. In concurrence with absence of hsp70 expression in the accessory glands of male fly, tissue damage was evident in them. Acp70A and Acp36DE expression were found to be significantly downregulated at the higher concentrations of the test chemicals. The study suggests that (i) Dichlorvos is more deleterious to fly reproduction compared to chlorpyrifos with an adverse effect on Acp70A and Acp36DE expression required to facilitate normal reproduction; (ii) hsp70 may be used as a marker of cellular damage against Dichlorvos and chlorpyrifos in Drosophila .
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hazardous effect of organophosphate compound Dichlorvos in transgenic drosophila melanogaster hsp70 lacz induction of hsp70 anti oxidant enzymes and inhibition of acetylcholinesterase
Biochimica et Biophysica Acta, 2005Co-Authors: Subash C Gupta, Hifzur R Siddique, D K Saxena, Debapratim Kar ChowdhuriAbstract:Abstract We tested a working hypothesis that stress genes and anti-oxidant enzyme machinery are induced by the organophosphate compound Dichlorvos in a non-target organism. Third instar larvae of Drosophila melanogaster transgenic for hsp70 were exposed to 0.1 to 100.0 ppb Dichlorvos and 5.0 mM CuSO4 (an inducer of oxidative stress and stress genes) and hsp70, and activities of acetylcholinesterase (AchE), superoxide dismutase (SOD), catalase (CAT) and lipid peroxidation (LPO) product were measured. The study was further extended to examine tissue damage, if any, under such conditions. A concentration- and time-dependent increase in hsp70 and anti-oxidant enzymes was observed in the exposed organism as compared to control. A comparison of stress gene expression with SOD, CAT activities and LPO product under similar experimental conditions revealed that induction of hsp70 precedes the anti-oxidant enzyme activities in the exposed organism. Further, concomitant with a significant inhibition of AChE activity, significant induction of hsp70 was observed following chemical exposure. Mild tissue damage was observed in the larvae exposed to 10.0 ppb Dichlorvos for 48 h when hsp70 expression reaches plateau. Dichlorvos at 0.1 ppb dietary concentration did not evoke significant hsp70 expression, anti-oxidant enzymes and LPO and AchE inhibition in the exposed organism, and thereby, was found to be non-hazardous to D. melanogaster. Conversely, 1.0 ppb of the test chemical stimulated a significant induction of hsp70 and anti-oxidant enzymes and significant inhibition of AchE; hence this concentration of test chemical was hazardous to the organism. The present study suggests that (a) both stress genes and anti-oxidant enzymes are stimulated as indices of cellular defense against xenobiotic hazard in D. melanogaster with hsp70 being proposed as first-tier bio-indicator of cellular hazard, (b) 0.1 ppb of the test chemical may be regarded as No Observed Adverse Effect Level (NOAEL), and 1.0 ppb Dichlorvos as Low Observed Adverse Effect Level (LOAEL).
C P Huang - One of the best experts on this subject based on the ideXlab platform.
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adsorption characteristics of Dichlorvos onto hydrous titanium dioxide surface
Water Research, 1996Co-Authors: Gwodong Roam, Jongnan Chen, C P HuangAbstract:Abstract Adsorption of Dichlorvos (2,2-dichlorovinyl-o,o-dimethl phosphate) onto hydrous TiO2 from water was evaluated in the laboratory using a batch reactor. The presence of organic solvents resulted in a decreasing Dichlorvos adsorption on TiO2 surface. These data were used to assess a cosolvent model. Decreased adsorption of Dichlorvos was observed at an initial pH of 4 with increasing ionic strength. The inhibitory adsorption is attributed to the blockade of surface sites by electrolytes. In addition, electrolytes play an important role on the pH-dependent Dichlorvos adsorption. It is suggested that at pH pHpzc, the adsorption density of Dichlorvos decreases with increasing solution pH due to the decrease of surface group, Ti OH, on the TiO2 surface. The variation of adsorption density with temperature over the range 10°–40°C has been investigated. Results show that the reaction is controlled by enthalpy. The adsorption of Dichlorvos onto the TiO2 surface is primarily brought about by hydrogen bonding.
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factors affecting the photocatalytic degradation of Dichlorvos over titanium dioxide supported on glass
Journal of Photochemistry and Photobiology A-chemistry, 1993Co-Authors: Gwodong Roam, Jongnan Chen, C P HuangAbstract:Abstract The photocatalytic degradation of organophosphorus insecticide, Dichlorvos, on glass-supported titanium dioxide was investigated. The photoreactor coated with titanium dioxide was illuminated with a 20 W black-light UV fluorescent tube. The aqueous solution containing Dichlorvos was continuously pumped through the photoreactor. Several factors, such as the initial Dichlorvos concentration, dissolved oxygen, electrolytes, flow rate and temperature, affecting the oxidation rate of Dichlorvos were studied. The results indicate that photocatalysis can be an effective process for the degradation of Dichlorvos. The activated energy for the photocatalytic degradation of Dichlorvos is 28.4 kJ mol−1. The initial quantum yield for the destruction of Dichlorvos is 2.67%. Increasing the flow rate and initial Dichlorvos concentration increases the Dichlorvos degradation rate. Total mineralization requires a much longer illumination time than the disappearance of Dichlorvos. Phosphate-containing intermediates are more stable than chloride-containing intermediates. It is shown that the photocatalytic oxidation of Dichlorvos follows the Langmuir—Hinshelwood-type behavior, and reaction byproducts display an inhibiting effect on degradation rate.
Subash C Gupta - One of the best experts on this subject based on the ideXlab platform.
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adverse effect of organophosphate compounds Dichlorvos and chlorpyrifos in the reproductive tissues of transgenic drosophila melanogaster 70 kda heat shock protein as a marker of cellular damage
Toxicology, 2007Co-Authors: Subash C Gupta, Hifzur R Siddique, D K Saxena, Neeraj Mathur, Ranjit K Mishra, Debapratim Kar ChowdhuriAbstract:Abstract The study highlights the adverse effects of organophosphate compounds Dichlorvos and chlorpyrifos on reproduction in Drosophila . Freshly eclosed first instar larvae of Drosophila melanogaster transgenic for hsp70 ( hsp70 - lacZ ) Bg 9 were fed on 0.015–150.0 ppb Dichlorvos and chlorpyrifos mixed food. Virgin flies eclosing from the normal and contaminated food were pair-mated to examine the effect of the test chemicals on reproduction of the exposed organisms. Expression of hsp70 , sex peptide (SP or Acp70A), accessory gland protein (Acp36DE) and tissue damage was examined in reproductive organs of adult fly. Exposed organisms exhibited a dose-dependent significantly reduced reproductive outcome and males were found to be more sensitive than females. Hsp70 expression was restricted only within the testis lobes of male fly while it was not induced in the ovary of the female. In concurrence with absence of hsp70 expression in the accessory glands of male fly, tissue damage was evident in them. Acp70A and Acp36DE expression were found to be significantly downregulated at the higher concentrations of the test chemicals. The study suggests that (i) Dichlorvos is more deleterious to fly reproduction compared to chlorpyrifos with an adverse effect on Acp70A and Acp36DE expression required to facilitate normal reproduction; (ii) hsp70 may be used as a marker of cellular damage against Dichlorvos and chlorpyrifos in Drosophila .
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hazardous effect of organophosphate compound Dichlorvos in transgenic drosophila melanogaster hsp70 lacz induction of hsp70 anti oxidant enzymes and inhibition of acetylcholinesterase
Biochimica et Biophysica Acta, 2005Co-Authors: Subash C Gupta, Hifzur R Siddique, D K Saxena, Debapratim Kar ChowdhuriAbstract:Abstract We tested a working hypothesis that stress genes and anti-oxidant enzyme machinery are induced by the organophosphate compound Dichlorvos in a non-target organism. Third instar larvae of Drosophila melanogaster transgenic for hsp70 were exposed to 0.1 to 100.0 ppb Dichlorvos and 5.0 mM CuSO4 (an inducer of oxidative stress and stress genes) and hsp70, and activities of acetylcholinesterase (AchE), superoxide dismutase (SOD), catalase (CAT) and lipid peroxidation (LPO) product were measured. The study was further extended to examine tissue damage, if any, under such conditions. A concentration- and time-dependent increase in hsp70 and anti-oxidant enzymes was observed in the exposed organism as compared to control. A comparison of stress gene expression with SOD, CAT activities and LPO product under similar experimental conditions revealed that induction of hsp70 precedes the anti-oxidant enzyme activities in the exposed organism. Further, concomitant with a significant inhibition of AChE activity, significant induction of hsp70 was observed following chemical exposure. Mild tissue damage was observed in the larvae exposed to 10.0 ppb Dichlorvos for 48 h when hsp70 expression reaches plateau. Dichlorvos at 0.1 ppb dietary concentration did not evoke significant hsp70 expression, anti-oxidant enzymes and LPO and AchE inhibition in the exposed organism, and thereby, was found to be non-hazardous to D. melanogaster. Conversely, 1.0 ppb of the test chemical stimulated a significant induction of hsp70 and anti-oxidant enzymes and significant inhibition of AchE; hence this concentration of test chemical was hazardous to the organism. The present study suggests that (a) both stress genes and anti-oxidant enzymes are stimulated as indices of cellular defense against xenobiotic hazard in D. melanogaster with hsp70 being proposed as first-tier bio-indicator of cellular hazard, (b) 0.1 ppb of the test chemical may be regarded as No Observed Adverse Effect Level (NOAEL), and 1.0 ppb Dichlorvos as Low Observed Adverse Effect Level (LOAEL).
Aditya Sunkaria - One of the best experts on this subject based on the ideXlab platform.
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Dichlorvos exposure results in activation induced apoptotic cell death in primary rat microglia
Chemical Research in Toxicology, 2012Co-Authors: Aditya Sunkaria, Willayat Yousuf Wani, Deep Raj Sharma, Kiran Dip GillAbstract:Dichlorvos [2,2-dichlorovinyl dimethyl phosphate] is one of the most common in-use organophosphate (OP) in developing nations. Previous studies from our lab have shown chronic Dichlorvos exposure leads to neuronal cell death in rats. However, the extent of damage caused by Dichlorvos to other cells of the central nervous system (CNS) is still not clear. Microglial cells are the primary threat sensors of CNS which become activated in many pathological conditions. Activation of microglial cells results in reactive microgliosis, manifested by increased cellular damage in the affected regions. Using rat primary microglial cultures, here we show that Dichlorvos exposure can activate and induce apoptotic cell death in microglia. We observed significant up-regulation of pro-inflammatory molecules like nitric oxide, TNF-α, and IL-1β when microglia were treated with Dichlorvos (10 μM). Significant up-regulation of CD11b, microglial specific activation marker, was also observed after 24 h of Dichlorvos treatment. The activated microglial cells eventually undergo cell death after 48 h of Dichlorvos treatment. The DNA fragmentation pattern of Dichlorvos treated microglia along with increased expression of Bax in mitochondria, cytochrome c release from mitochondria, and caspase-3 activation led us to assume that microglia were undergoing apoptosis. Thus, the present study showed that Dichlorvos can induce microglial activation and ultimately apoptotic cell death. These findings gave new perspective to the current knowledge of Dichlorvos (OPs) mediated CNS damage and presents microglial activation as a potential therapeutic target for preventing the OP induced neuronal damage.
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protective efficacy of mitochondrial targeted antioxidant mitoq against Dichlorvos induced oxidative stress and cell death in rat brain
Neuropharmacology, 2011Co-Authors: Willayat Yousuf Wani, Satish Gudup, Aditya Sunkaria, Parvinder Pal Singh, Deep Raj Sharma, Ramesh Kandimalla, Kiran Dip GillAbstract:Abstract Dichlorvos is a synthetic insecticide that belongs to the family of chemically related organophosphate (OP) pesticides. It can be released into the environment as a major degradation product of other OPs, such as trichlorfon, naled, and metrifonate. Dichlorvos exerts its toxic effects in humans and animals by inhibiting neural acetylcholinesterase. Chronic low-level exposure to Dichlorvos has been shown to result in inhibition of the mitochondrial complex I and cytochrome oxidase in rat brain, resulting in generation of reactive oxygen species (ROS). Enhanced ROS production leads to disruption of cellular antioxidant defense systems and release of cytochrome c (cyt c) from mitochondria to cytosol resulting in apoptotic cell death. MitoQ is an antioxidant, selectively targeted to mitochondria and protects it from oxidative damage and has been shown to decrease mitochondrial damage in various animal models of oxidative stress. We hypothesized that if oxidative damage to mitochondria does play a significant role in Dichlorvos induced neurodegeneration, then MitoQ should ameliorate neuronal apoptosis. Administration of MitoQ (100 μmol/kg body wt/day) reduced Dichlorvos (6 mg/kg body wt/day) induced oxidative stress (decreased ROS production, increased MnSOD activity and glutathione levels) with decreased lipid peroxidation, protein and DNA oxidation. In addition, MitoQ also suppressed DNA fragmentation, cyt c release and caspase-3 activity in Dichlorvos treated rats compared to the control group. Further electron microscopic studies revealed that MitoQ attenuates Dichlorvos induced mitochondrial swelling, loss of cristae and chromatin condensation. These results indicate that MitoQ may be beneficial against OP (Dichlorvos) induced neurodegeneration.