Cellular metabolism and health impacts of dichlorvos: Occurrence, detection, prevention, and remedial strategies-A review.

Dichlorvos (2,2-Dichlorovinyl dimethyl phosphate, [DDVP]) belongs to the class of organophosphates and is widely used as an insecticide in agriculture farming and post-harvest storage units. Extensive research has been conducted to assess the factors responsible for the presence of DDVP in terrestrial and aquatic ecosystems, as well as the entire food chain. Numerous studies have demonstrated the presence of DDVP metabolites in the food chain and their toxicity to mammals. These studies emphasize that both immediate and chronic exposure to DDVP can disrupt the host's homeostasis, leading to multi-organ damage. Furthermore, as a potent carcinogen, DDVP can harm aquatic systems. Therefore, understanding the contamination of DDVP and its toxicological effects on both plants and mammals is vital for minimizing potential risks and enhancing safety in the future. This review aimed to comprehensively consolidate information about the distribution, ecological effects, and health impacts of DDVP, as well as its metabolism, detection, prevention, and remediation strategies. In summary, this study observes the distribution of DDVP contaminations in vegetables and fruits, resulting in significant toxicity to humans. Although several detection and bioremediation strategies are emerging, the improper application of DDVP and the alarming level of DDVP contamination in foods lead to human toxicity that requires attention.

Study on the acute toxicity of trichlorfon and its breakdown product dichlorvos to goldfish (Carassius auratus) based on 1H NMR metabonomics.

Trichlorfon, one of the most widely used organophosphate insecticides, is commonly employed in aquaculture and agriculture to combat parasitic infestations. However, its inherent instability leads to rapid decomposition into dichlorvos (DDVP), increasing its toxicity by eightfold. Therefore, the environmental effects of trichlorfon in real-world scenarios involve the combined effects of trichlorfon and its degradation product, DDVP. In this study, we systematically investigated the degradation of trichlorfon in tap water over time using HPLC and LC-MS/MS analysis. Subsequently, an experiment was conducted to assess the acute toxicity of trichlorfon and DDVP on goldfish (Carassius auratus), employing a 1H NMR-based metabolic approach in conjunction with serum biochemistry, histopathological inspection, and correlation network analysis. Exposure to trichlorfon and its degradation product DDVP leads to increased lipid peroxidation, reduced antioxidant activity, and severe hepatotoxicity and nephrotoxicity in goldfish. Based on the observed pathological changes and metabolite alterations, short-term exposure to trichlorfon significantly affected the liver and kidney functions of goldfish, while exerting minimal influence on the brain, potentially due to the presence of the blood-brain barrier. The changes in the metabolic profile indicated that trichlorfon and DDVP influenced several pathways, including oxidative stress, protein synthesis, energy metabolism, and nucleic acid metabolism. This study demonstrated the applicability and potential of 1H NMR-based metabonomics in pesticide environmental risk assessment, providing a feasible method for the comprehensive study of pesticide toxicity in water environments.

Biochemical and gene expression alterations due to individual exposure of atrazine, dichlorvos, and imidacloprid and their combination in zebrafish.

In environmental toxicology, combined toxicity has emerged as an important concern. Atrazine (ATZ), dichlorvos (DIC), and imidacloprid (IMD) are the major pesticides, extensively used to control insect, flies, mosquitoes, and weed. Here, we investigate whether the exposure to three different types of pesticides individually and in combination for 24 h alters antioxidant enzyme responses in zebrafish (Danio rerio). Oxidative stress parameters (biochemical and mRNA expression), acetylcholinesterase (AChE) activity, and Metallothionein-II (MT-II) mRNA expression levels were measured. Present work includes toxicological assessment of individual and combined (CMD) exposure of ATZ (185.4 µM), DIC (181 µM), IMD (97.8 µ), and CMD (ATZ 92.7 µM + DIC 90.5 µM + IMD 48.9 µM), in the liver, kidney, and brain of adult zebrafish. Lipid peroxidation (LPO), glutathione (GSH) content, AChE, superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activity along with mRNA expression of SOD, CAT, GPx, and MT-II were evaluated. Briefly, LPO, GSH content, the activity of AChE, and all antioxidant enzymes enhanced significantly in individual exposure, which was further altered in the CMD group. The mRNA expression of SOD, CAT, GPx, and MT-II in the liver and kidney showed significant down-regulation in all exposed groups. In the brain, significant upregulation in mRNA expression of SOD, CAT, GPx, and MT-II was observed in DIC and IMD groups, while ATZ and CMD showed significant downregulation except for GPx. Findings postulate that the CMD group exhibits synergistic toxic manifestation. The present study provides the baseline data on the combined toxic effects of pesticides and suggests regulating the use of pesticides.

Effects of Dichlorvos on cardiac cells: Toxicity and molecular mechanism of action.

In this study we aimed to understand the underlying mechanism of Dichlorvos-induced toxicity in cardiac cells. For this end, cells were treated by 170 µM of Dichlorvos (DDVP) (corresponding to the IC50) and molecular events were monitored by flow cytometry and western blotting. We have first demonstrated that cell exposure to DDVP for 24 h induced cell death by necroptosis. In fact, cell treatment with DDVP upregulated RIP1 expression and we have shown that chemical inhibition of RIP1 kinase activity by necrostatin-1 (Nec-1) greatly prevented from the induced cell death. Besides, we have demonstrated that, while there was no observed cell death following short exposure to DDVP (6 h), autophagy was enhanced, as proven by the increase in the level of both Beclin-1 and LC3-II and the accumulation of the CytoID® autophagy detection probe. Besides, when autophagy was inhibited by chloroquine (CQ) the percentage of necroptosis was significantly increased, suggesting that autophagy acts to protect cardiac cells against the toxicity induced by this pesticide. Concurrently, we have shown that the inhibition of the deacetylase sirtuin 1 (SIRT1) by EX527 or its knockdown by siRNA significantly increased DDVP-induced necroptosis, whereas when SIRT1 was activated by resveratrol (RSV) a significant decrease in DDVP-induced cell death was observed. In addition, we revealed that when the autophagy was inhibited by CQ, we can't reveal the protective effect of RSV anymore. Altogether, these results suggest that activation of SIRT1 protects cardiac cells from the toxicity of DDVP through an autophagy-dependent pathway.

Effects of short-term exposure to volatile pesticide dichlorvos on the olfactory systems in Spodoptera litura: Calcium homeostasis, synaptic plasticity and apoptosis.

Volatile pesticides are a growing environmental and public health concern. However, little attention has been paid to its olfactory neurotoxic effect on pests and non-target organisms. Dichlorvos is a widely used organophosphorus fumigant that is ubiquitous in the environment. This study aims to explore the mode of action of the volatile dichlorvos-mediated olfactory impairment using a lepidopteran insect Spodoptera litura as a model. It was indicated that electroantennogram amplitudes of the male moths' response to sex pheromones and phenylacetaldehyde were reduced by approximately 20 % after 12-h fumigation exposure. RNA-Sequencing analysis revealed that down-regulation of trypsin and CLIC2 might be responsible for inhibition of odor recognition in the antenna, the peripheral olfactory tissue. In the head, 822 (84.05 %) of the 978 differentially expressed genes (DEGs) were up-regulated, of which seven DEGs encoding transcription factors may mainly modulate the stress-regulatory networks. Combining transcriptome with brain calcium imaging and Annexin V-mCherry staining experiments showed that volatile dichlorvos mainly disrupts Ca2+ homeostasis and synaptic plasticity, induces apoptosis in the central nervous system, and further leads to olfactory dysfunction. Overall, this study highlighted a comprehensive work model for dichlorvos-induced olfactory impairment in S. litura and may provide insights into toxic effects of airborne organophosphates on non-target organisms.

SAHmap: Synergistic-antagonistic heatmap to evaluate the combined synergistic effect of mixtures of three pesticides on multiple endpoints of Caenorhabditis elegans.

The environmental pollution caused by toxic chemicals such as pesticides has become a global problem. The mixture of dichlorvos (DIC), dimethoate (DIM), aldicarb (ALD) poses potential risks to the environment and human health. To fully explore the interaction of complex mixtures on Caenorhabditis elegans behavioral toxicity endpoint. This study created a synergistic-antagonistic heatmap (SAHmap) based on the combination index to systematically describe the toxicological interaction prospect of the mixture system. It was shown that the three pesticides and their binary as well as ternary mixture rays have significant concentration-response relationship on three behavioral endpoints of nematodes, From the perspective of synergistic-antagonistic heatmaps, all the mixture rays in the DIC-DIM mixture system showed strong synergism on the three behavioral and lethal endpoints. In the ternary mixture system, the five mixture rays showed different interaction between the behavioral endpoint and the lethal endpoint, and showed slight synergism to two behavioral endpoints as a whole. The emergence of synergism should arouse our attention to these hazardous chemicals. In addition, the use of SAHmap and the significant linear correlation among three behavioral endpoints further improved the efficiency of the study on the behavioral toxicity of pesticide mixtures to Caenorhabditis elegans.

Photocatalytic activity of graphene oxide-TiO2 nanocomposite on dichlorvos and malathion and assessment of toxicity changes due to photodegradation.

Heterogeneous photocatalysis was used for the removal of two widely used organophosphorus pesticides, dichlorvos, and malathion from water. Graphene oxide-TiO2 nanocomposite (GOT) was synthesized and used as a photocatalyst for the removal of these pesticides. Batch studies for optimizing photocatalytic degradation and mineralization of pesticides over 80 min were conducted by varying the pH (2-10), catalyst dose (20 mg/L-200 mg/L), and initial pesticide concentration (0.5 mg/L-20 mg/L), and the irradiation source (125 W UV and visible lamp). Degradation kinetics for the pesticides were evaluated. Ellman assay was used to estimate the toxic effect of pesticides and evaluate toxicity reduction due to treatment. The highest degradation and mineralization of dichlorvos and malathion was observed at pH 6 and the optimum catalyst dose was 60 mg/L. Under UV irradiation, 80% and 90% degradation were observed for dichlorvos and malathion, respectively for 0.5 mg/L initial pesticide concentration. The photocatalytic degradation reaction followed Langmuir-Hinshelwood kinetics. A high degree of mineralization was achieved for both the pesticides. Analysis of the results revealed that the residual toxic effect after photocatalysis was primarily due to the residual parent compound. A comparative study revealed that GOT yielded better pesticide degradation compared to commercially available TiO2 under both UV and visible irradiation.

Chlorpyrifos and dichlorvos in combined exposure reveals antagonistic interaction to the freshwater fish Mrigal, Cirrhinus mrigala.

Toxicity imposed by organophosphate pesticides to the freshwater cultivable fish species mrigal (Cirrhinus mrigala) was assessed under laboratory conditions. Healthy juveniles were exposed to chlorpyrifos, dichlorvos, and their equitoxic mixture in geometric series. Median lethal concentrations of chlorpyrifos were found to be 0.906 (0.689-1.179), 0.527 (0.433-0.633), 0.435 (0.366-0.517) and 0.380 (0.319-0.450) mg/L and dichlorvos were found to be 38.432 (33.625-47.866), 22.477 (19.047-26.646), 12.442 (9.619-14.196) and 11.367 (9.496-13.536) mg/L after 24 h, 48 h, 72 h and 96 h of exposure respectively. Surprisingly, the joint toxicity of these organophosphates in the binary mixture was less than additive during most of the exposure periods. Behavioral changes exhibited by individual as well as mixture pesticide treatments were loss of schooling behavior, aggregating at corners of the test chamber, elevated opercular beatings, surplus mucus secretion, slight color changes and sudden and rapid body movements before death. Loss of fish equilibrium was noticed only in chlorpyrifos treated fish, whereas sluggish behavior was noticed only in mixture pesticide treatment. Such behavioral studies can be applied as a non-invasive bio-monitoring tool for water quality assessment for fish growth and development. Despite the same mode of action of both pesticides, the antagonistic action in the binary mixture is an interesting outcome of this research that requires further investigation for a lucid understanding of the joint toxicity mechanism of such pesticides.

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.

Olfactory dysfunction and potential mechanisms caused by volatile organophosphate dichlorvos in the silkworm as a model animal.

Volatile pesticides impair olfactory function in workers/farmers and insects, but data on molecular responses and mechanisms are poorly understood. This study aims to reveal the mechanisms of olfactory dysfunction in the silkworm after exposure to volatile dichlorvos. Our results demonstrated that acute exposure for 12 h significantly reduced electroantennogram responses, and over 62.50% of the treated male moths cannot locate the pheromone source. Transcriptional and proteomic responses of the antennae and heads were investigated. A total of 101 differentially expressed genes (DEGs) in the antennae, 138 DEGs in the heads, and 43 differentially expressed proteins (DEPs) in the heads including antennae were revealed. We discovered that upregulations of Arrestin1 and nitric oxide synthase1 (NOS1) may inhibit cyclic nucleotide-gated channels and hinder calcium influx in the antennae. In the central nervous systems (CNS), downregulations of tyrosine hydroxylase (TH) and tyrosine decarboxylase (TDC) may inhibit olfactory signal transduction by reducing the second messenger biosynthesis. Meanwhile, an abnormal increase of brain cell apoptosis was revealed by Annexin V-mCherry staining, often leading to persistent neurologic impairment. Taken together, this study highlighted olfactory dysfunction caused by dichlorvos, which may provide a novel perspective for understanding the toxicity mechanism of volatile pesticides in other organisms.

Effects of subchronic inhalation exposure to an organophosphorus insecticide compound containing dichlorvos on wistar rats' otoacoustic emissions.

INTRODUCTION: Considering that previous studies suggest that pesticides may cause hearing disorders in humans, as well as the lack of studies proving the specific mechanisms of injury and the difficulty of separating concomitant etiological factors of the hearing damage, such as noise and vibration, it is important to develop studies using animal models to elucidate the effects of exposure to those substances isolated from other hearing damage etiologies. OBJECTIVE: To evaluate if the exposure to a dichlorvos based organophosphorus insecticide may induce ototoxicity. METHODS: 36 male Wistar rats were assigned to 3 groups (12 rats/group): control (exposed to water), positive control (treated with cisplatin to induce hearing damage) and experimental (exposed to dichlorvos based organophosphorus insecticide). The amplitude of distortion product otoacoustic emissions in the frequencies of 4, 6, 8, 10 and 12kHz was evaluated before and after exposure, as well as systemic toxicity signs, body mass gain and plasma cholinesterase. Open field and plus maze tests were performed in 24 rats: experimental (n=8), control (n=8) and positive control group (n=8 introduced new rats to induce anxiolytic activity) to evaluate the locomotor activity and anxiety, respectively. RESULTS: There was no significant change in body mass gain and plasma cholinesterase in the dichlorvos based organophosphorus insecticide group, however, the animals showed transient piloerection, depression and dyspnea during exposure. The behavior was not affected in any group. The frequencies of 8 and 10kHz were significantly affected bilaterally in the insecticide group, which also showed a significant difference of the control in 10kHz on the right and 8 and 10kHz on the left ear. CONCLUSION: Subchronic inhalation exposure to dichlorvos based organophosphorus insecticide induced ototoxicity in the cochlear function of rats without relevant systemic toxicity.

Transient exposure to sublethal concentrations of a pesticide mixture (chlorpyrifos-difenoconazole) caused different responses in fish species from different trophic levels of the same community.

The assessment of early effects caused in biota by sublethal exposure to pesticide mixtures should enhance the realism in the ecological risk assessment for agricultural landscapes. This study aimed to evaluate sub-individual responses in fish, which can be linked with outcomes at higher levels of biological organization and affect their trophic relationships. A multilevel biomarker approach was applied to assess the effects of a 48 h exposure of two freshwater mesoamerican fish species (Parachromis dovii and Poecilia gillii) to a mixture of sublethal concentrations of chlorpyrifos (5 µg/L) and difenoconazole (325 µg/L). Transcriptomic induction of cyp1A and the activities of 7-ethoxy-resorufin-O-distillase (EROD) and glutathione S-transferase (GST) were measured as biotransformation-related biomarkers; cholinesterase activity (ChE) was assessed as a neurotoxicity biomarker; resting metabolic rate (RMR) was measured as a physiological biomarker; and the movement of fish in a dark-light environment as a behavior biomarker. The exposure to the mixture had evident effects on P. gillii, with significant induction of cyp1A transcription, increased EROD activity, ChE inhibition in muscle, and increased permanence in the light side of the dark-light environment. Meanwhile, P. dovii only showed significant induction of cyp1A, without evidence of neurotoxicity or changes in behavior. This study demonstrates that the severity of the effects caused by the exposure to a mixture of pesticides can differ among species from the same trophic chain. The potential impairment of predator-prey relationships is a relevant effect that pesticide pollution can cause and it should be considered for the risk assessment of such contaminants.

Modulations of blood biochemical parameters of golden mahseer, Tor putitora following exposures to single and mixed organophosphate.

Increasing pesticide application is a serious threat to human health and biodiversity. In nature, pesticides prevail in mixtures; therefore the joint effects of pesticides should be taken into consideration due to their priority in toxicity research when aiming at realistic evaluations. In this study, individual and mixture toxicity of the commonly used organophosphate insecticides- chlorpyrifos and dichlorvos was explored. Healthy and clinically active juveniles of golden mahseer (Tor putitora) were exposed to sub-lethal doses (10% of the 96 h-LC50) of the chlorpyrifos, dichlorvos, and their mixture. Blood sampling was conducted after 24 h and 96 h of exposure, followed by a 1 week recovery period. Among the examined biochemical parameters; blood glucose in dichlorvos treatment; alanine aminotransferase and alkaline phosphatase in chlorpyrifos and dichlorvos treatments; and aspartate aminotransferase and urea in mixture pesticide treatments were elevated. In contrast, blood albumin and triglycerides were diminished in mixture pesticide treatments. Vital organs like kidney and liver of the tested animals were compromised to different magnitudes in different pesticide treatments. Kidney was found to be more sensitive than liver in terms of pesticide toxicity during this short exposure experiment. This study revealed that most of the biomarkers were mainly affected at a later exposure phase (after 96 h) and steadily recovered during the depuration period.

Dichlorvos poisoning caused chicken cerebrum tissue damage and related apoptosis-related gene changes.

Dichlorvos (DDVP) is an organophosphorus compound with insecticidal effects. Organophosphorus pesticides can easily enter humans or animals through various channels, causing cerebrum nerve cell damage. The purpose of this research was to investigate whether acute dichlorvos poisoning can cause cerebrum neurotoxic injury and change the expression of apoptosis-related genes in broilers, further clarify the neurotoxic mechanism after acute dichlorvos exposure, and provide a research basis for prevention, treatment and gene drug screening in the later stage. In this experiment, healthy yellow-feathered broilers were randomly assigned to the control group, the low-dose group (1.13 mg/kg) and the high-dose group (10.2 mg/kg) for modelling observation, and detection was conducted based on H&E (haematoxylin and eosin) staining, transmission electron microscopy analysis of tissue sections, immunofluorescence techniques and real-time quantitative polymerase chain reaction (qRT-PCR). The results showed that organophosphorus poisoning was accompanied by obvious neurological symptoms such as limb twitching and massive salivation. In addition, we observed that compared with the control group, the number of lysed nuclear neurons, deformed vascular sheaths, and glial cells and the expression of glial fibrillary acidic protein (GFAP) in the poisoned group of broilers increased significantly, and the increase was more obvious in the low-dose group. However, cell apoptosis and mitochondrial structure dissolution were most pronounced in the high-dose group. Moreover, the qRT-PCR results also revealed significant changes in the expression of apoptosis-related genes. The expression levels of ACC, LKB1 and GPAT increased significantly, while the expression of HMGR, PPARα, CPT1 and AMPKα1 decreased significantly. In summary, these results indicated that dichlorvos may cause the lysis of cerebrum nerve cell nuclei, completely destroy the structure of mitochondria, change the expression of related apoptotic genes, enhance cell apoptosis, and cause neurogenic damage to the cerebrum. These research results offer a theoretical foundation for the prevention and treatment of acute organophosphate toxicosis.

Suppression of uric acid generation and blockade of glutathione dysregulation by L-arginine ameliorates dichlorvos-induced oxidative hepatorenal damage in rats.

Dichlorvos is a known risk factor for organ toxicity. The liver and kidney are essential metabolic tissues but it is unclear whether or not there is associated redox dyshomeostasis in both organs in physiological and pathological states. Uric acid accumulation and glutathione dysregulation have been implicated in the aetiopathogenesis of organ damage. The antioxidant potentials of L-arginine have been shown in various conditions. The present study was thus designed to investigate the synchrony in hepatic and renal uric acid and glutathione status in dichlorvos-induced hepatorenal damage and to probe the possible therapeutic role of L-arginine. Twenty-one male Wistar rats were treated with standard rat diet and water, dichlorvos, or dichlorvos and L-arginine. Our findings revealed that dichlorvos significantly impaired hepatic and renal functions, increased hepatic and renal malondialdehyde, but reduced glutathione and activities of superoxide dismutase, catalase, and glutathione peroxidase. These events were accompanied by increased accumulation of plasma, hepatic, and renal uric acid as well as reduced body weight gain, and hepatic and renal weights. Histopathological examinations revealed hepatic and renal architectural derangement and cellular necrosis and degeneration in dichlorvos-exposed rats. Interestingly, L-arginine reversed dichlorvos-induced systemic, hepatic and renal synchronous redox dyshomeostasis. L-arginine administration also improved hepatic and renal cytoarchitecture. It is thus concluded that dichlorvos triggered synchronous uric acid generation and glutathione alterations in the liver and kidney. L-arginine confers protection against dichlorvos-induced hepatorenal damage via suppression of uric acid generation and blockade of glutathione dysregulation.

In vivo assessment of dichlorvos induced histological and biochemical impairments coupled with expression of p53 responsive apoptotic genes in the liver and kidney of fish, Channa punctatus (Bloch, 1793).

Sub-lethal exposure of dichlorvos induces oxidative stress, consequent genetic instability and apoptosis coupled with impairments in biochemical, histopathological and transcription of genes in Channa punctatus. Exposure of 5% (0.041 mg/L; E2) and 10% (0.082 mg/L; E3) of 96 h-LC50 of dichlorvos significantly (p < 0.05) elevated the reactive oxygen species (ROS) generation and activities of SOD and CAT, as compared to control (E1) after 30 d. The maximum reduction in reduced glutathione (GSH) was recorded in the liver (18.53 ± 0.81 µg/mg of protein) and kidney (19.32 ± 0.97 µg/mg of protein); while the total protein contents were also found reduced, 278.38 ± 8.40 µg/mL (liver) and 248.44 ± 7.28 µg/mL (kidney), after 30 days in E3, in comparison to respective controls. Further, significant (p < 0.05) induction in micronuclei (MN) and apoptotic cells (AC), in a dose- and exposure-based manner were also recorded. Moreover, a significant (p < 0.05) up-regulation of p53 (2.51-fold in liver), bax (2.03-fold in liver; 1.99-fold in kidney) and casp3a (2.26-fold in liver; 2.10-fold in kidney) together with an elevated expression of cat (1.73-fold in liver; 1.12-fold in kidney), p53 (1.27-fold in kidney) and apaf-1 (1.72-fold in liver) in fish exposed to higher dose of dichlorvos for 30 d evidently reflects geno-toxicological potential of referenced pesticide. Disturbed biochemical and molecular parameters evince that the fish experienced oxidative stress as is further supported by prominent pathological observations in liver and kidney. Findings are, thus, helpful in organ-specific molecular scanning against aquatic toxicants like dichlorvos.

Defensive proclivity of bacoside A and bromelain against oxidative stress and AChE gene expression induced by dichlorvos in the brain of Mus musculus.

The objective of current study was to evaluate the neuroprotective effects of bacoside A and bromelain against dichlorvos induced toxicity. The healthy, 6-8 weeks old male Swiss mice were administered in separate groups subacute doses of dichlorvos (40 mg/kg bw), bacoside A (5 mg/kg bw) and bromelain (70 mg/kg bw). In order to determination of oxidative stress in different groups, thiobarbituric acid reactive substances (TBARS) and protein carbonyl content (PCC) were studied in the present investigation. Moreover, for toxic manifestation at molecular level the site-specific gene amplification of acetylcholinesterase (AChE) gene was studied in the brain. Nonetheless, the protective effects of bacoside A and bromelain were also evaluated on the TBARS, PCC and AChE gene. The exposure of dichlorvos leads to significant increase in TBARS level (p < 0.01, p < 0.001) and PCC. Besides, the decline in DNA yield, expression of amplified products of AChE gene was observed in the brain of dichlorvos treated group. The bacoside A and bromelain treatments significantly decreased the level of TBARS (p < 0.05, (p < 0.01) and PCC whereas, increase in the DNA yield and expression of amplified AChE gene products were observed in the brain compared to only dichlorvos treated mice. The overall picture which emerged after critical evaluation of results indicated that the dichlorvos induced oxidative stress and alteration in AChE gene expression showed significant improvement owing to the treatments of bacoside A and bromelain. Thus, bacoside A and bromelain are very effective in alleviating neurotoxicity induced by dichlorvos.

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.

Joint toxicity assessment reveals synergistic effect of chlorpyrifos and dichlorvos to common carp (Cyprinus carpio).

Common carp (Cyprinus carpio) is an important aquaculture species. However, their production and health is sometimes threatened by pesticides. In common carp, extensive studies have been done for exposures of single pesticides, but effects of mixtures such as those of the commonly used chlorpyrifos and dichlorvos, are still unknown for this species. In the first phase of this work, an acute lethal exposure experiment was conducted to estimate 24 h to 96 h lethal concentrations (LC10-90) of chlorpyrifos, dichlorvos and their mixture. Compared to dichlorvos, chlorpyrifos was found to be highly toxic to the tested species. Joint toxicity assessment of these pesticides in binary mixtures was dominated by synergism. In the second experimental phase, common carp were exposed to sub-lethal concentrations (LD-10% and HD-50% 96 h-LC50) of individual pesticides and their mixture. General fish behaviors, buccal movements and feeding attempts by fish were recorded after 1 h, 24 h, 48 h, 72 h and 96 h whereas aerobic metabolism of fish was recorded for 0-24 h, 24-48 h 48-72 h and 72-96 h of exposure. All pesticide treatments elevated buccal movements and oxygen uptake in a dose dependent manner. Feeding depression was also observed by pesticide exposure. The augmented deleterious effect of these pesticides in a mixture suggests that joint toxicity assessment is critical to develop more realistic water quality standards and monitoring guidelines.

The Effect of Organophosphate Exposure on Neuronal Cell Coenzyme Q10 Status.

Organophosphate (OP) compounds are widely used as pesticides and herbicides and exposure to these compounds has been associated with both chronic and acute forms of neurological dysfunction including cognitive impairment, neurophysiological problems and cerebral ataxia with evidence of mitochondrial impairment being associated with this toxicity. In view of the potential mitochondrial impairment, the present study aimed to investigate the effect of exposure to commonly used OPs, dichlorvos, methyl-parathion (parathion) and chloropyrifos (CPF) on the cellular level of the mitochondrial electron transport chain (ETC) electron carrier, coenzyme Q10 (CoQ10) in human neuroblastoma SH-SY5Y cells. The effect of a perturbation in CoQ10 status was also evaluated on mitochondrial function and cell viability. A significant decreased (P < 0.0001) in neuronal cell viability was observed following treatment with all three OPs (100 µM), with dichlorvos appearing to be the most toxic to cells and causing an 80% loss of viability. OP treatment also resulted in a significant diminution in cellular CoQ10 status, with levels of this isoprenoid being decreased by 72% (P < 0.0001), 62% (P < 0.0005) and 43% (P < 0.005) of control levels following treatment with dichlorvos, parathion and CPF (50 µM), respectively. OP exposure was also found to affect the activities of the mitochondrial enzymes, citrate synthase (CS) and mitochondrial electron transport chain (ETC) complex II+III. Dichlorvos and CPF (50 µM) treatment significantly decreased CS activity by 38% (P < 0.0001) and 35% (P < 0.0005), respectively compared to control levels in addition to causing a 54% and 57% (P < 0.0001) reduction in complex II+III activity, respectively. Interestingly, although CoQ10 supplementation (5 µM) was able to restore cellular CoQ10 status and CS activity to control levels following OP treatment, complex II+III activity was only restored to control levels in neuronal cells exposed to dichlorvos (50 µM). However, post supplementation with CoQ10, complex II+III activity significantly increased by 33% (P < 0.0005), 25% (P < 0.005) and 35% (P < 0.0001) in dichlorvos, parathion and CPF (100 µM) treated cells respectively compared to non-CoQ10 supplemented cells. In conclusion, the results of this study have indicated evidence of neuronal cell CoQ10 deficiency with associated mitochondrial dysfunction following OP exposure. Although CoQ10 supplementation was able to ameliorate OP induced deficiencies in CS activity, ETC complex II+III activity appeared partially refractory to this treatment. Accordingly, these results indicate the therapeutic potential of CoQ10 supplementation in the treatment of OP poisoning. However, higher doses may be required to engender therapeutic efficacy.