DDVP Exposure Research Articles

Hesperetin-7-rutinoside mitigates erythrocyte dyslipidemia and oxidative stress induced by dichlorvos

In many rural and semi-urban areas of Nigeria, dichlorvos (DDVP) is a commonly utilized pesticide. However, it provokes remarkable health hazards, including erythrocyte toxicity. Hesperetin-7-rutinoside (Hesp-7-Rut), a citrus flavanone glycoside with antioxidant, anti-dyslipidemia and acetylcholinesterase-modulating properties has been investigated for its protective effects against various xenobiotic-mediated toxicities. This inquiry probed the chemotherapeutic role of Hesp-7-Rut in mitigating erythrocyte damage in rats. Forty-two rats were randomly `apportioned into seven groups (6 rats/group): control, DDVP alone (8 mg.kg⁻¹day⁻¹), DDVP + Hesp-7-Rut (50 mg.kg⁻¹day⁻¹), DDVP + Hesp-7-Rut (100 mg.kg⁻¹day⁻¹), DDVP + atropine (0.2 mg.kg⁻¹day⁻¹), Hesp-7-Rut only (50 mg.kg⁻¹day⁻¹), and Hesp-7-Rut only (100 mg.kg⁻¹day⁻¹). Rats were orally administered DDVP for 7 days followed by Hesp-7-Rut or atropine for another 14 days. Blood samples were collected to assess for biochemical assays. Hesp-7-Rut significantly (p < 0.05) rescinded DDVP-prompted increases in erythrocyte nitric oxide, malondialdehyde, cholesterol, phospholipids, and cholesterol: phospholipids ratio. Additionally, Hesp-7-Rut reversed DDVP-elicited decreases in red blood cell glutathione levels, activities of GST, SOD, catalase, glutathione peroxidase, and acetylcholinesterase. Overall, Hesp-7-Rut efficiently counteracts DDVP-elicited erythrocyte dysfunction by mitigating oxidative stress, dyslipidemia, and acetylcholinesterase inhibition. These findings highlight the potential of Hesp-7-Rut as a promising therapeutic agent for mitigating the harmful effects of DDVP exposure.

The Liver of Young and Old Female Rats Exhibits Heightened Susceptibility to Dichlorvos Exposure

Exposure to industrial and agricultural environmental contaminants has been shown to produce deleterious effects on different organs of the human body. Dichlorvos [O, O-dimethyl O-(2,2-dichlorovinyl) phosphate, DDVP] is a major organophosphate pesticide used mostly in developing countries for domestic and agricultural insect control. The toxic effects of DDVP have been reported on many organs. However, its gender and age-dependent effects on the liver are yet to be documented. This study investigated the influence of gender and age on liver damage in male and female rats exposed to DDVP. Animals were divided into control and experimental groups with age and gender classification. Using age, rats were classified into young, middle-aged, and old age groups. Rats in the experimental groups were exposed to DDVP from 8 am to 12 noon for five weeks. Rats were subsequently euthanized and liver tissues were harvested for biochemical assay. Glutamyl transferase (GGT), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Alkaline phosphatase (ALP), Lactate dehydrogenase (LDH), Albumin, and conjugated bilirubin were assayed using ELISA kits. Statistical analysis was done using two-way ANOVA, followed by Tukey post-Hoc test at significance level of p&lt;0.05. Our study found that DDVP exposure caused liver damage in female rats only with significant elevation in liver enzymes such as ALP, ALT, AST, and LDH. However, the male rats showed more resistance to DDVP exposure. The liver damage observed in female rats was age-dependent, with young and old rats showing higher susceptibility compared to middle-aged female rats. Nutritional and pharmacological strategies are recommended to mitigate the effect of DDVP exposure, particularly in populations at higher risk of exposure.

Ginger (Zingiber officinale) attenuates the neurotoxicity in rats induced by organophosphate pesticide

BackgroundWe are exposed to different chemicals in various ways in our daily life, and these can be toxic at minute concentrations. The pesticides used for different purposes are also toxic and may pose threat to life by inducing oxidative stress. Dichlorvos (DDVP) is an organophosphate pesticide used for various purposes and is also reported to be toxic. In this study, the neurotoxicity of DDVP exposure was studied. The role of ginger, Zingiber officinale (ZO), was also evaluated against the neurotoxic effects of DDVP. Forty-eight Wistar rats of both the sexes were used in this study. The rats were exposed to DDVP and post-treatment with ZO was given. The oxidative stress in terms of lipid peroxidation (LPO), reduced glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione reductase (GR) levels were estimated after exposure and treatment.ResultsDDVP resulted in oxidative stress, evidenced by enhanced LPO level. The simultaneous reductions in other non-enzymatic and enzymatic antioxidants were reported. The post-treatment with ZO led to a reduction in oxidative stress in rat brains. The levels of SOD, CAT, GSH, GR, and GPx were increased whereas declined levels of LPO were reported after treatment.ConclusionHence, ginger can help mitigate the pesticide toxicity through the up-regulation of antioxidant levels.

Nigella sativa Oil Preserved Anxiety-Like, Motor and Memory Related Behaviours and Neuronal Integrity in Dichlorvos Induced Acetyl Cholinesterase Inhibitions in Rats

Organophosphates are irreversible cholinesterase (ChE) inhibitors with neurological consequences, and there is not yet an effective antidote. Here, we investigated the effects of Nigella sativa oil (NSO) on the ChE inhibition, neurobehavioural and histopathological changes following dichlorvos (DDVP) ingestions in rats. Thirty-two male Wistar rats were randomised into four groups, receiving 1 ml/kg of normal saline, 8.8 mg/kg of DDVP, 8.8 mg/kg of DDVP and 1 ml/kg of NSO, and 1 ml/kg of NSO only respectively, for 14 consecutive days. Locomotor, anxiety-like behaviours and spatial working memory were assessed on the 14th day, using open field (OF), Y-maze and modified elevated plus maze paradigms. The rats were euthanized on the 15th day and the brains excised; three brains were fixed for histopathology, and the other five prepared for biochemical analysis of acetyl cholinesterase (AChE). DDVP exposure caused significant reductions in frontal, amygdala and cerebella AChE activity, spontaneous alternations, line crossing and rearing frequencies and time in centre square, and caused increase in freezing period, transfer latency and necrotic-like cells. NSO intervention was able to reverse DDVP effects on AChE activities, explorative, locomotor, anxiety and spatial memory behaviours in co-exposed rats. It also preserved the histological integrity of the investigated brain regions. It can be concluded that NSO, may be potent against organophosphates induced neurotoxicity and their neurobehavioural consequences through the modulation of AChE activities.

Correlation between acute brain injury and brain metabonomics in dichlorvos-poisoned broilers

Dichlorvos (DDVP) is an insecticide with neurotoxicity that is widely used in agricultural production and life. However, the effects of acute DDVP poisoning on brain tissue remain underinvestigated. The purpose of this study was to evaluate the differences within 15 min-6 h in plasma biochemical indexes, brain histology and metabolites among three groups of commercial broilers orally administered different dosages of DDVP one time: (1) high-dose group (11.3 mg/kg), (2) low-dose group (2.48 mg/kg) and (3) control group (0 mg/kg). The results of biochemical indexes showed that acute DDVP poisoning could cause hyperglycemia and oxidative stress in poisoned broilers. Histological examination showed that DDVP could induce brain edema, abnormal expression of glial fibrillary acidic protein (GFAP) and neuronal mitochondrial damage in broilers. Whole-brain metabolism showed that DDVP could significantly change the secretion of neurotransmitters, energy metabolism, amino acid metabolism and nucleotide metabolism. Correlation analysis showed that metabolites such as hypoxanthine, acetylcarnitine and glucose 6-phosphate were significantly correlated with blood glucose, biomarkers of oxidative stress and brain injury pathology. The results of this study provide new insights into the molecular mechanism of brain tissue responses to acute DDVP exposure in broilers and deliver important information for clinical research on neurodegenerative diseases caused by acute DDVP poisoning.

Non-linear model analysis of the relationship between cholinesterase activity in rats exposed to 2, 2-dichlorovinyl dimethylphosphate (dichlorvos) and its metabolite concentrations in urine

Urinary dialkylphosphates (DAPs) are measured to assess exposure to organophosphorus pesticides (OPs), but they are common metabolites of OPs and not specific indices for individual agents. Biomonitoring (BM) of urinary DAPs has been widely adopted as an assessment of individual exposure in general environments, however, guidance values for DAPs based on health effects have yet to be established. The present study aimed to clarify the relationship between the amount of urinary dimethylphosphate (DMP), a metabolite of dichlorvos (DDVP), and the inhibition of cholinesterase (ChE) activity in rats exposed to DDVP. The relationship was analyzed using a nonlinear model analysis, and the excretion level of urinary DMP equivalent to ChE 20 % inhibition (EL20) and the lower limit of the 95 % confidence interval of EL20 (ELL20) were estimated. EL20 and ELL20 (mg/24 h urine) of brain, erythrocyte, and plasma ChE activities after 10-day administration of DDVP were 0.21 and 0.15, 0.11 and 0.06, and 0.23 and 0.09, respectively. Extrapolating ELL20 of the brain ChE to humans, the range of 24 h urinary DMP concentration according to the 20 % inhibition of cholinesterase activity was estimated to be 20.5–30.8 mg/l. In conclusion, the amount of urinary DMP as ELL20 for DDVP exposure was identified and could probably be used as a novel index for the assessment of risk from OP exposure. Further studies are needed to clarify the ELL20 s derived from OPs other than DDVP, for informing efforts to establish guidance values of urinary OP metabolites that should prevent neurotoxicity.

Moringa oleifera seed oil partially abrogates 2,3-dichlorovinyl dimethyl phosphate (Dichlorvos)-induced cardiac injury in rats: evidence for the role of oxidative stress.

Cardiovascular diseases are major causes of non-infectious diseases globally. The use of pesticides hasbeen linked with the high global burden of non-communicable diseases. Despite the indiscriminate exposure to dichlorvos (DDVP) by inhalation, no report exists on its possible cardiotoxic effect. This study investigated the cardiotoxicity of DDVP exposure by inhalation and the possible role ofMoringa oleiferaseed oil. Twenty-one male rats were randomly assigned into 3 groups. Group A (control) received only standard rat diet and water ad' libitum, group B (DDVP) was exposed to DDVP via inhalation for 15min daily in addition to rat diet and water, and group C (DDVP+M. oleifera seed oil) received treatment as group B as well as 300mg/kg of M. oleifera seed oil p.o for 28days. Significant reductions in body weight gain and cardiac weight were observed inDDVP-exposed animals (p<0.05). Similarly, 28days of exposure to DDVP led to a significant increase in lactate dehydrogenase, creatinine kinase and troponin (p<0.05). DDVP-exposed rats also showed a significant increase in malondialdehyde, and a significant decline in superoxide dismutase and glutathione peroxidase (p<0.05). However, catalase was comparable in DDVP-exposed and control rats. Histopathological observations of the cardiac tissue revealed that DDVP caused marked fat degeneration and necrosis of the myocardial layer. The changes in DDVP-exposed rats were significantly, though not completely, restored by M.oleifera seed oil administration. This study provides novel mechanistic information on the cardiotoxicity of DDVP inhalation, and the antioxidant potential of M.oleifera seed oil.

The detoxifying effect of Polygonum equisetiforme extracts against dichlorvos (DDVP)-induced oxidative stress and neurotoxicity in the commercial clam Ruditapes decussatus.

Effects of Polygonum equisetiforme extracts against dichlorvos were investigated in the commercial clam Ruditapes decussatus. The toxicity of this pesticide was firstly tested in R. decussatus gill and digestive gland tissues using five doses varying from 0.05 to 1mg/l during 2, 4, and 7days. Results showed that 0.05mg/l of DDVP induced oxidative stress and neurotoxicity in R. decussatus after 2days of exposure. Investigations of the effects of P. equisetiforme extracts in R. decussatus exposed to 0.25mg/l of DDVP were made in clams receiving three concentrations (0.009, 0.045, and 0.09g/l) during 4 and 7days. Antioxidant enzymes SOD and CAT as well as H2O2 content and AChE were quantified by colorimetric method. Fourdays of exposure to DDVP increased SOD and CAT activities and enhances H2O2 content. AChE levels decreased considerably following DDVP exposure, although a restoration in the enzyme activity was observed with P. equisetiforme extract (E3 = 0.09g/l). Overall, P. equisetiforme extract at concentration (E1 = 0.009g/l) prevents oxidative stress caused by DDVP, while 0.09g/l of P. equisetiforme extract induced an effect similar to that obtained with DDVP alone. Nevertheless, this concentration was found effective for the restoration of the AChE activity.

Nigella sativa oil protected the hippocampus against Acetyl cholinesterase and oxidative dysfunctions-driven impaired working memory in rats

Oxidative damages in organophosphates poisoning is associated with neuro-cognitive deficits. This study investigates the protective effect of Nigella sativa oil (NSO) in mitigating dichlorvos (DDVP) induced oxidative damage and neuro-cognitive impairment in rats. Thirty-two rats were randomly divided into four groups, exposed to 1 ml/kg of normal saline, 8.8 mg/kg of DDVP, DDVP + 1 ml/kg of NSO and NSO respectively for 14 consecutive days. Body weights were recorded at day 1 and 15 of the experiment, the rats were exposed to 3 trials each on the 11, 12 and 13th days in the Morris water maze, and subsequently latency to hidden platform and time in the platform quadrant were recorded as measures of long term memory (LTM), short term memory (STM) and reference memory on the 14th day. The rats were euthanized on the 15th day, the brains excised and the hippocampi of five brains in each group were removed, homogenized to analyze for total reactive oxygen species (ROS), nitrous oxide (NO) levels and acetylcholinesterase (AChE) activities, while the other three were processed for histology and Ki67 immunohistochemistry. DDVP exposure caused a significant increase in hippocampal NO and ROS levels, with reductions in AChE activities and Ki67 protein expression. This was associated with delayed escape latency and reduced time in platform quadrant. NSO intervention prevented outburst in ROS and NO, preserved the neurogenic cells and improved neuro-cognitive indices. We thus conclude that stabilizing oxidative and neurogenic functions are vital to protect against DDVP hippocampal insults.

Chlorpyrifos- and Dichlorvos-Induced Oxidative and Neurogenic Damage Elicits Neuro-Cognitive Deficits and Increases Anxiety-Like Behavior in Wild-Type Rats.

The execution of agricultural activities on an industrial scale has led to indiscriminate deposition of toxic xenobiotics, including organophosphates, in the biome. This has led to intoxication characterized by deleterious oxidative and neuronal changes. This study investigated the consequences of oxidative and neurogenic disruptions that follow exposure to a combination of two organophosphates, chlorpyrifos (CPF) and dichlorvos (DDVP), on neuro-cognitive performance and anxiety-like behaviors in rats. Thirty-two adult male Wistar rats (150–170 g) were randomly divided into four groups, orally exposed to normal saline (NS), DDVP (8.8 mg/kg), CPF (14.9 mg/kg), and DDVP + CPF for 14 consecutive days. On day 10 of exposure, anxiety-like behavior and amygdala-dependent fear learning were assessed using open field and elevated plus maze paradigms, respectively, while spatial working memory was assessed on day 14 in the Morris water maze paradigm, following three training trials on days 11, 12, and 13. On day 15, the rats were euthanized, and their brains excised, with the hippocampus and amygdala removed. Five of these samples were homogenized and centrifuged to analyze nitric oxide (NO) metabolites, total reactive oxygen species (ROS), and acetylcholinesterase (AChE) activity, and the other three were processed for histology (cresyl violet stain) and proliferative markers (Ki67 immunohistochemistry). Marked (p ≤0.05) loss in body weight, AChE depletion, and overproduction of both NO and ROS were observed after repeated exposure to individual and combined doses of CPF and DDVP. Insults from DDVP exposure appeared more severe owing to the observed greater losses in the body weights of exposed rats. There was also a significant (p ≤0.05) effect on the cognitive behaviors recorded from the exposed rats, and these deficits were related to the oxidative damage and neurogenic cell loss in the hippocampus and the amygdala of the exposed rats. Taken together, these results provided an insight that oxidative and neurogenic damage are central to the severity of neuro-cognitive dysfunction and increased anxiety-like behaviors that follow organophosphate poisoning.

Functional characterization of the ABC transporter TaPdr2 in the tolerance of biocontrol the fungus Trichoderma atroviride T23 to dichlorvos stress

For successful biological control interactions, biological control organisms need to tolerate toxic chemical pesticides present in the environment. Dichlorvos (DDVP) is one of the most widely used organophosphorus pesticides and is also used as a model organophosphorus pesticide to understand the tolerance mechanism of biocontrol agent to chemical fungicides. In this study, we focused on the contribution of one ATP-binding cassette (ABC) transporter in Trichoderma atroviride that results in tolerance to DDVP stress. The gene encoding the protein, designated TaPdr2, was amplified from the T. atroviride T23 genome using homologous cloning and identified by induction to DDVP exposure. The sequence analysis of TaPdr2 predicted that this gene was a typical ABC-G transporter and may have functions, such as serving as a pleiotropic drug resistance protein (PDR) phenotype for xenobiotic tolerance and biocontrol traits. The key role of this gene in the tolerance to DDVP was demonstrated by the characterization of deletion mutants obtained by the ATMT-mediated knockout of homologous recombination. By analyzing the difference in growth phenotype between ΔTaPdr2 and the wild type (WT) strain, we found that ΔTaPdr2 led to a significant decline in Trichoderma tolerance to DDVP. Similarly, the ergosterol content in the ΔTaPdr2 cell membrane was also significantly reduced compared with the WT strain. The electrolyte leakage rate of the WT and ΔTaPdr2 under DDVP stress was higher than that of DDVP-free treatment. However, the electrolyte leakage rate was not significantly different between the mutant ΔTaPdr2 and the WT in the presence of DDVP. These data showed that the transporter TaPdr2 contributes to DDVP tolerance in T. atroviride T23.

Xuebijing injection induces anti-inflammatory-like effects and downregulates the expression of TLR4 and NF-κB in lung injury caused by dichlorvos poisoning

BackgroundThe mechanism in lung injury caused by acute organophosphate pesticide poisoning (AOPP) and an effective treatment remains unclear. We aim to clarify how the inflammatory lung injury caused by AOPP might be modulated by Xuebijing (XBJ) injection. MethodsAOPP-induced lung injury model was induced by dichlorvos (DDVP) subcutaneous administration in rats and XBJ injection was administered by intraperitoneal injection after DDVP challenge. The effects of XBJ injection were assessed by lung histopathological analysis and lung injury scores, lung wet-to-dry weight ratios (WDR) and oxygenation, differential immune cell count in bronchoalveolar lavage fluid (BALF), IL-6 and TNF-α levels in blood, the levels of TLR4 and NF-κB proteins in lung tissue and blood acetylcholinesterase (AChE) activity. ResultsDDVP administration resulted in damage of lung histopathology and lower PaO2/FiO2 ratios (P < 0.05), which were notably attenuated by XBJ injection (P < 0.05). Total cell, macrophage, and neutrophils count in BALF and TNF-α and IL-6 levels in blood were significantly increased after DDVP exposure (P < 0.05), which were notably ameliorated by XBJ injection (P < 0.05). TLR4 and NF-κB protein in lung tissue expression after DDVP challenge were markedly increased (P < 0.05), and they were substantially downregulated by XBJ injection (P < 0.05). In addition, blood AChE activity was significantly decreased by DDVP administration (P < 0.05), however, there was no significant improvement after XBJ injection. ConclusionXBJ injection prevents DDVP poisoning induced lung injury by attenuating the inflammatory response. The protective effect appears to be mediated through downregulation of the TLR4 and NF-κB expression.

Histopathological and Biochemical evaluations of the antidotal efficacy of &lt;i&gt;Nigella sativa&lt;/i&gt; oil on organophosphate induced hepato-toxicity

Objective: The study was designed to investigate the effects of continuous exposure of dichlorvos (DDVP) on hepatic function and hepatic histomorphology, with the possible antidotal efficacy of Nigella sativa oil (NSO).Methods: Twenty four Wistar rats were randomly divided into four groups, with each group comprising of six rats. The groups were labelled as Sunflower oil (SFO), DDVP, DDVP+NSO and NSO. After 14 days of treatments, blood samples were collected, centrifuged and levels of ALP (Alkaline phosphatase), ALT (Alanine aminotransferase), AST (Aspartate aminotransferase) and GGT (γ-glutamyl-transferase) concentrations were estimated in the serum. The livers were removed and prepared for histopathological examinations and evaluation.Results: The findings of the study shows significant increase in the serum concentration of ALT, ALP, AST and GGT with a marked distortion in the hepatic architecture in rats administered with DDVP. However, Nigella sativa oil (NSO) was observed to ameliorate the levels of impairment in the assessed hepatic function parameters and relatively restoration in the hepatic architecture in DDVP+NSO treated animals when compared to the control and group administered with DDVPonly.Conclusion: The study concludes that impaired liver functions and histomorphological tissue distortions observed in the experimental rats following DDVP exposure were ameliorated following theadministration of NSO.Keywords: Nigella sativa, dichlorvos, antidotal effect, hepatotoxicity, liver function test

Protection studies of new bis quaternary 2-(hydroxyimino)-N-(pyridin-3yl) acetamide derivatives (HNK-series) oximes against acute poisoning by dichlorvos (DDVP) in Swiss albino mice.

The available antidotal therapy against acute poisoning by organophosphates involves the use of atropine alone or in combination with one of the oximes, e.g. 2-PAM, Obidoxime, TMB-4 or HI-6. Each of these oximes has some limitation, raising the question of the universal antidotal efficacy against poisoning by all OPs/nerve agents. In the present study, newly synthesized bis quaternary 2-(hydroxyimino)-N-(pyridin-3yl) acetamide derivatives (HNK-series) oximes were evaluated for their antidotal efficacy against DDVP intoxicated Swiss mice, in terms of the Protection Index (PI) and AChE reactivation in brain and serum. The inhibition concentration (IC50) was determined in brain and serum after optimizing the time point for maximum inhibition (60 min post DDVP exposure). AChE reactivation efficacy of the HNK series was evaluated at IC50 and compared with 2-PAM. HNK-102 showed a ~2 times better Protection Index (PI) as compared to 2-PAM against DDVP toxicity. IC50 at 60 min DDVP post exposure was found to be approximately one fifth and one half of the LD50 dose for brain and serum AChE, respectively. Out of three HNK oximes, HNK-102 & 106 at 0.20 LD50 dose significantly reactivated DDVP intoxicated brain AChE (p<0.05) as compared to 2-PAM at double IC50 dose of DDVP. In light of double PI and higher AChE reactivation, HNK 102 was found to be a better oxime than 2-PAM in the treatment of acute poisoning by DDVP.

Therapeutic and reactivating efficacy of oximes K027 and K203 against a direct acetylcholinesterase inhibitor

As oxime-based structures are the only causal antidotes to organophosphate (OP)-inhibited acetylcholinesterase (AChE), the majority of studies on these have been directed towards their synthesis and testing. In this study, experimental bispyridinium oximes K027 and K203, which have shown promising results in the last decade of research, were examined in vivo for their therapeutic and reactivating ability in acute poisoning by the direct AChE-inhibitor dichlorvos (DDVP), used as a dimethyl OP structural model. Additionally, the efficacy of oximes K027 and K203 was compared with the efficacy of four oximes (pralidoxime, trimedoxime, obidoxime and HI-6), already used in efficacy experiments and human medicine. To evaluate therapeutic efficacy, groups of Wistar rats were treated with equitoxic doses of oximes (5% LD50, i.m.) and/or atropine (10mg/kg, i.m.) immediately after s.c. DDVP challenge (4–6 doses). Using the same antidotal protocol, AChE activity was measured in erythrocytes, diaphragm and brain 60min after s.c. DDVP exposure (75% LD50). The oxime K027 was the most efficacious in reducing the DDVP induced lethal effect in rats, while the oxime K203 was more efficacious than trimedoxime, pralidoxime and HI-6. Significant reactivation of DDVP inhibited AChE was achieved only with oxime K027 or its combination with atropine in erythocytes and the diaphragm. Moreover, the acute i.m. toxicity of oxime K027 in rats was lower than all other tested oximes. The results of this study support previous studies considering the oxime K027 as a promising experimental oxime structure for further testing against structurally-different OP compounds.

Crocin, the main active saffron constituent, mitigates dichlorvos-induced oxidative stress and apoptosis in HCT-116 cells.

The protective effects of Crocin (CRO), a carotenoid with wide spectrum of pharmacological effects, against the cytotoxicity and the apoptosis produced by exposure to Dichlorvos (DDVP) in HCT116 cells were investigated in this work. The cytotoxicity was monitored by cell viability, ROS generation, antioxidant enzymes activities, malondialdehyde (MDA) production and DNA fragmentation. The apoptosis was assessed through the measurement of the mitochondrial transmembrane potential (ΔΨm) and caspases activation. The results indicated that pretreatment of HCT116 cells with CRO, 2h prior to DDVP exposure, significantly increased the survival of cells, inhibited the ROS generation, modulated the activities of catalase (CAT) and superoxide dismutase (SOD) and reduced the MDA level. The reduction in mitochondrial membrane potential, DNA fragmentation and caspases activation were also inhibited by CRO. These findings suggest that CRO can protect HCT116 cells from DDVP-induced oxidative stress and apoptosis.

Dichlorvos exposure results in large scale disruption of energy metabolism in the liver of the zebrafish, Danio rerio

BackgroundExposure to dichlorvos (DDVP), an organophosphorus pesticide, is known to result in neurotoxicity as well as other metabolic perturbations. However, the molecular causes of DDVP toxicity are poorly understood, especially in cells other than neurons and muscle cells. To obtain a better understanding of the process of non-neuronal DDVP toxicity, we exposed zebrafish to different concentrations of DDVP, and investigated the resulting changes in liver histology and gene transcription.ResultsFunctional enrichment analysis of genes affected by DDVP exposure identified a number of processes involved in energy utilization and stress response in the liver. The abundance of transcripts for proteins involved in glucose metabolism was profoundly affected, suggesting that carbon flux might be diverted toward the pentose phosphate pathway to compensate for an elevated demand for energy and reducing equivalents for detoxification. Strikingly, many transcripts for molecules involved in β-oxidation and fatty acid synthesis were down-regulated. We found increases in message levels for molecules involved in reactive oxygen species responses as well as ubiquitination, proteasomal degradation, and autophagy.To ensure that the effects of DDVP on energy metabolism were not simply a consequence of poor feeding because of neuromuscular impairment, we fasted fish for 29 or 50 h and analyzed liver gene expression in them. The patterns of gene expression for energy metabolism in fasted and DDVP-exposed fish were markedly different.ConclusionWe observed coordinated changes in the expression of a large number of genes involved in energy metabolism and responses to oxidative stress. These results argue that an appreciable part of the effect of DDVP is on energy metabolism and is regulated at the message level. Although we observed some evidence of neuromuscular impairment in exposed fish that may have resulted in reduced feeding, the alterations in gene expression in exposed fish cannot readily be explained by nutrient deprivation.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-015-1941-2) contains supplementary material, which is available to authorized users.

Quercetin protects HCT116 cells from Dichlorvos-induced oxidative stress and apoptosis.

The present study was designed to assess the possible protective effects of Quercetin (QUER), a flavonoid with well-known pharmacological effects, against Dichlorvos (DDVP)-induced toxicity in vitro using HCT116 cells. The cytotoxicity was monitored by cell viability, reactive oxygen species (ROS) generation, anti-oxidant enzyme activities, malondialdehyde (MDA) production, and DNA fragmentation. The apoptosis was assessed through the measurement of the mitochondrial transmembrane potential (ΔΨm) and caspase activation. The results indicated that pretreatment of HCT116 cells with QUER, 2 h prior to DDVP exposure, significantly decreased the DDVP-induced cell death, inhibited the ROS generation, modulated the activities of catalase (CAT) and superoxide dismutase (SOD), and reduced the MDA level. The reductions in mitochondrial membrane potential, DNA fragmentation, and caspase activation were also attenuated by QUER. These findings suggest that dietary QUER can protect HCT116 cells against DDVP-induced oxidative stress and apoptosis.

Alterations in Antioxidant Enzyme Activity, Lipid Peroxidation, and Ion Balance Induced by Dichlorvos inGalleria mellonella(Lepidoptera: Pyralidae): Table 1.

ABSTRACT Dichlorvos (DDVP; 2,2-dichlorovinyl dimethyl phosphate) is an organophosphate insecticide widely used in the control of pests. This study aims to determine the changes caused by DDVP in the antioxidant enzyme activity, lipid peroxidation level, and ion content of a model organism, Galleria mellonella L. (Lepidoptera: Pyralidae). Larvae of G. mellonella were fed sublethal concentrations of DDVP (2, 4, 6, and 8 µg/l00 g feed). Exposure to DDVP resulted in induction of superoxide dismutase and catalase activities, and lipid peroxidation in larvae. Potassium and sodium ion levels were significantly altered by DDVP exposure. These results suggest that DDVP causes oxidative stress and lipid peroxidation and alters the antioxidant enzyme activities and ion balance in G. mellonella larvae. Additionally, these results indicate that G. mellonella is a useful model for testing the effects of insecticides.

Efficacy of methuselah gene mutation toward tolerance of dichlorvos exposure in Drosophila melanogaster

Adverse reports on the exposure of organisms to dichlorvos (DDVP; an organophosphate insecticide) necessitate studies of organismal resistance/tolerance by way of pharmacological or genetic means. In the context of genetic modulation, a mutation in methuselah (mth; encodes a class II G-protein-coupled receptor (GPCR)) is reported to extend (~35%) the life span of Drosophila melanogaster and enhance their resistance to oxidative stress induced by paraquat exposure (short term, high level). A lack of studies on organismal tolerance of DDVP by genetic modulation prompted us to examine the protective efficacy of mth mutation in exposed Drosophila. Flies were exposed to 1.5 and 15.0ng/ml DDVP for 12–48h to examine oxidative stress endpoints and chemical resistance. After prolonged exposure of flies to DDVP, antioxidant enzyme activities, oxidative stress, glutathione content, and locomotor performance were assayed at various days (0, 10, 20, 30, 40, 50) of age. Flies with the mth mutation (mth1) showed improved chemical resistance and rescued redox impairment after acute DDVP exposure. Exposed mth1 flies exhibited improved life span along with enhanced antioxidant enzyme activities and rescued oxidative perturbations and locomotor insufficiency up to middle age (~20 days) over similarly exposed w1118 flies. However, at late (≥30 days) age, these benefits were undermined. Further, similarly exposed mth-knockdown flies showed effects similar to those observed in mth1 flies. This study provides evidence of tolerance in organisms carrying a mth mutation against prolonged DDVP exposure and further warrants examination of similar class II GPCR signaling facets toward better organismal health.