Diazinon Exposure Research Articles

Protective effect of thymoquinone, the main component of Nigella Sativa, against diazinon cardio-toxicity in rats

Several studies have shown that oxidative stress and cell damage can occur at very early stages of diazinon (DZN) exposure. The present study was designed to determine the beneficial effect of thymoquinone (Thy), the main component of Nigella sativa (black seed or black cumin), against DZN cardio-toxicity in rats. In the present experimental study, 48 male Wistar rats were randomly divided into six groups: control (corn oil gavages), DZN gavages (20 mg/kg/day), Thy gavages (10 mg/kg/day) and Thy + DVN gavages (2.5, 5 and 10 mg/kg/day). Treatments were continued for 28 days, then the animals were anesthetized by ether and superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST), lactate dehydrogenize (LDH) and glutathione peroxide (GPX) activity was evaluated. In addition, glutathione (GSH) and malondialdehyde (MDA) the heart tissue and creatinephosphokinase-MB (CPK-MB) and troponin (TPI) levels and cholinesterase activity in the blood were evaluated. DZN-induced oxidative damage and elevated the levels of the cardiac markers CK-MB, TPI, MDA and LDH and decreased SOD, CAT and cholinesterase activity and GSH level compared with the control group. Treatment with Thy reduced DZN cardio-toxicity and cholinesterase activity. The success of Thy supplementation against DZN toxicity can be attributed to the antioxidant effects of its constituents. Administration of Thy as a natural antioxidant decreased DZN cardio-toxicity and improved cholinesterase activity in rats through the mechanism of free radical scavenging.

Alteration of hepatocellular antioxidant gene expression pattern and biomarkers of oxidative damage in diazinon-induced acute toxicity in Wistar rat: A time-course mechanistic study.

In the present survey, the plasma level of diazinon after acute exposure was measured by HPLC method at a time-course manner. In addition, the impact of diazinon on the expression of the key genes responsible for hepatocellular antioxidative defense, including PON1, GPx and CAT were investigated. The increase in oxidative damages in treated rats was determined by measuring LPO, protein carbonyl content and total antioxidant power in plasma. After administration of 85 mg/kg diazinon in ten groups of male Wistar rats at different time points between 0-24 hours, the activity of AChE enzyme was inhibited to about 77.94 %. Significant increases in carbonyl groups and LPO after 0.75 and 1 hours were also observed while the plasma antioxidant power was significantly decreased. Despite the dramatic reduction of GPX and PON1 gene expression, CAT gene was significantly upregulated in mRNA level by 1.1 fold after 4 hours and 1.5-fold after 24 hours due to diazinon exposure, compared to control group. Furthermore, no significant changes in diazinon plasma levels were found after 4 hours in the treated rats. The limits of detection and quantification were 137.42 and 416.52 ng/mL, respectively. The average percentage recoveries from plasma were between 90.62 % and 95.72 %. In conclusion, acute exposure to diazinon increased oxidative stress markers in a time-dependent manner and the changes were consistent with effects on hepatic antioxidant gene expression pattern. The effect of diazinon even as a non-lethal dose was induced on the gene expression of antioxidant enzymes. The change in antioxidant defense system occurs prior to diazinon plasma peak time. These results provide biochemical and molecular evidence supporting potential acute toxicity of diazinon and is beneficial in the evaluation of acute toxicity of other organophosphorus pesticides as well.

Gene expression analysis reveals chronic low level exposure to the pesticide diazinon affects psychological disorders gene sets in the adult rat

Chronic low level exposure to organophosphate (OPs) pesticides in adulthood has been linked to adverse neurobehavioural deficits and psychological disorder symptoms, although this remains a contentious issue. The OP-induced biological changes that could underlie these effects are unclear. We assessed gene expression changes following chronic low level exposure to diazinon, a pesticide with a high dietary exposure risk. Adult male rats were orally exposed to diazinon (0, 1, 2mg/kg, 5days a week for 12 weeks). After 4 weeks, marble burying behaviour was lower in diazinon exposed rats than vehicle exposed rats; this difference persisted for 8 weeks. Chronic diazinon exposure did not significantly inhibit acetylcholinesterase activity, the primary mechanism of action of high level OPs. Affymetrix GeneChip® HT RG-230 PM Arrays were used for gene profiling followed by Ingenuity Pathway analysis. In the hippocampus, the most significant gene expression changes caused by OP exposure were associated with Psychological Disorders, and Cell-To-Cell Signalling and Interaction functions. Genes encoding the AMPA3 glutamate receptor, glutaminase, dopamine transporter and tyrosine hydroxylase were up-regulated, whereas the gene encoding the GABAB1 receptor was down-regulated. In the dorsal raphe nucleus, genes associated with development and the Psychological Disorders function were significantly affected, including the up-regulation of the gene encoding the α1b-adrenoceptor, the major driver of serotoninergic (5-HT) neuronal activity. These data indicate that chronic exposure to diazinon in adulthood, below the threshold to inhibit acetylcholinesterase, stimulates glutamatergic, dopaminergic and serotonergic synaptic transmission which may underlie adverse neurological outcomes.

Protective effect of thymoquinone against diazinon-induced hematotoxicity, genotoxicity and immunotoxicity in rats

Several studies have shown that oxidative stress and cell damage can occur in the very early stages of diazinon (DZN) exposure. The present study was designed to determine the beneficial effect of thymoquinone (Thy), the main component of Nigella sativa (black seed or black cumin) against DZN immunotoxicity, hematotoxicity and genotoxicity in rats. In the present experimental study, 48 male Wistar rats were randomly divided into six groups, (eight per group) as follows: control (receiving corn oil as the DZN solvent), DZN (20mg/kg), Thy (10mg/kg), Thy (2.5mg/kg)+DZN, Thy (5mg/kg)+DZN and Thy (10mg/kg)+DZN. After four weeks of treatment, the hematological parameters of red blood cells (RBCs), white blood cells (WBCs), hemoglobin (Hb), hematocrit (Hct) and platelets (PLTs) were evaluated. The evaluation of genotoxicity was carried out using the micronucleus assay. For measurement of cytokine production, interferon gamma (IFN-γ), interleukin 10 (IL10) and interleukin 4 (IL4) were chosen as immunotoxicity indicators of DZN toxicity. DZN was found to decrease RBCs, WBCs, Hb, Hct, PLTs, butyrl- and acetyl-cholinesterase activity and I FN-γ and increased the micronucleus indices of IL10 and IL4 as compared with the control group. Treatment with Thy reduced DZN hematotoxicity and immunotoxicity, but, significantly, did not prevent genotoxicity. This study showed that Thy (without the significant effect on genotoxicity) decreased the hematological toxicity, immunotoxicity and butyrl and acetyl cholinesterase activity induced by DZN. The success of Thy supplementation against DZN toxicity can be attributed to the antioxidant effects of its constituents.

Effects of Acute Exposure of Diazinon on the Ovarian Steroidogenesis in Chicken, Gallus gallus

Diazinon (DZN) is an organophosphate insecticide has been used widely in agriculture to control pests. DZN has been found to induce reproductive dysfunctions in animals, particularly, avian species. This current study evaluated the lethal effects of acutely ingested DZN on the ovaries of laying hens. Twenty white leghorn laying hens were divided equally into two groups. Group one was kept as a control, and the second group was administrated orally with a single dose of DZN (6 mg/kg B.W) for twenty one days. At end of the experiment, serum and tissue samples (ovaries) were collected for hormonal and histopathological analysis. The results revealed that body weight was not affected significantly by DZN treatment. However, DZN treated group exhibited destructive changes in folliculogenesis, degeneration of ovarian follicles, and stromal hemorrhage in comparison with the control group. Additionally, significant changes of steroidal hormonal levels were observed with a significant increase in serum progesterone and decrease in estrogen in the treated group as compared to the control group. Therefore, the current reduction of serum estrogen in our study could be due to the destructive effects of DZN on ovarian tissues and/or its ability to alter the expression of P450 aromatase, the enzyme which is involved in estrogen production. In the contrary, serum progesterone levels increased significantly. This increase might be due to the activation of some steroidogenic enzymes such as 3β-hydroxy-steroid dehydrogenase (3β-HSD) by ovarian secondary follicles. In conclusion, this current study showed that acute oral administration of DZN induces destructive structural changes in ovary and changes in female sex steroid hormone levels in blood. This lethal effect of DZN may lead to the infertility in laying hens, thus economic lose and health impact.

Molecular quantitative assay for esterase-mediated organophosphate resistance in Rhipicephalus microplus

The use of pesticides is the main tool to control infestations of the cattle tick Rhipicephalus microplus, and organophosphate (OP) is one of the most used compounds for this purpose. Carboxylesterases (ChEs) are targets for OP pesticides in arthropods, and acetylcholinesterase 2 (AChE2) and esterase 1 (EST1) are metabolic enzymes involved in the xenobiotic detoxification process. The increase in the synthesis of these enzymes can be detected by the quantitative polymerase chain reaction (qPCR) assay, which was used to identify cattle tick populations resistant to OP pesticides. For that, two field populations of R. microplus were used, one previously identified by the larval packet test (LPT) as OP −sensitive (LC50=0.13μg/cm2) and the other OP-resistant (LC50=8.14μg/cm2). To promote the OP enzyme detoxification, groups of 10 females of the resistant strain were immersed in solutions of diazinon in technical grade at concentrations of 1.0mg/ml, 2.5mg/ml, and 5.0mg/ml. The ticks that survived diazinon exposure were submitted to qPCR assay, which enabled observing an increase in AChE2 and EST1 synthesis in the OP-resistant strain when compared to the susceptible strain. The initial results of expression analysis suggest that the qPCR assay can discriminate OP-resistant and susceptible populations. The development and improvement of molecular diagnostic tests to identify pesticide resistant R. microplus populations are priorities and in the near future it will be important to expand the molecular targets involved in OP resistance, which could be used for better selection of effective strategies to control cattle tick populations.

Editor's Highlight: OrganophosphateDiazinon Altered Quorum Sensing, Cell Motility, Stress Response, and Carbohydrate Metabolism of Gut Microbiome.

The gut microbiome plays a key role in energy production, immune system development, and host resistance against invading pathogens, etc. Disruption of gut bacterial homeostasis is associated with a number of human diseases. Several environmental chemicals have been reported to induce alterations of the gut microbiome. Diazinon, one of important organophosphate insecticides, has been widely used in agriculture. Diazinon and its metabolites are readily detected in different environmental settings and human urine. The toxicity of organophosphates has been a long-standing public health concern. We recently demonstrated that organophosphate insecticide diazinon perturbed the gut microbiome composition of mice. However, the functional impact of exposure on the gut microbiome has not been adequately assessed yet. In particular, the molecular mechanism responsible for exposure-induced microbial profile and community structure changes has not been identified. Therefore, in this study, we used metatranscriptomics to examine the effects of diazinon exposure on the gut metatranscriptome in C57BL/6 mice. Herein, we demonstrated for the first time that organophosphate diazinon modulated quorum sensing, which may serve as a key mechanism to regulate bacterial population, composition, and more importantly, their functional genes. In addition, we also found that diazinon exposure activated diverse stress response pathways and profoundly impaired energy metabolism of gut bacteria. These findings provide new understandings of the functional interplay between the gut microbiome and environmental chemicals, such as organophosphates.

Protective effects of cerium oxide and yttrium oxide nanoparticles on reduction of oxidative stress induced by sub-acute exposure to diazinon in the rat pancreas

Diazinon is a kind of organophosphorus (OP) compound that is broadly used against different species of insects and pests. Oxidative stress can occur at very early stages of diazinon exposure and the pancreas is one of the main target organs for toxicity by diazinon. The aim of this study was to evaluate the protective effects of cerium oxide nanoparticles (CeO2 NPs) and yttrium oxide nanoparticles (Y2O3 NPs) against the pancreatic damage from sub-acute exposure of diazinon. Diazinon at a dose of 70mg/kg/day was given through gavage to rats once a day. Along with diazinon, trace amounts of CeO2 NPs and Y2O3 NPs (35mg/kg and 45mg/kg per day, respectively) were administered by intraperitoneal injection once a day for 2 weeks. Animals weight and blood glucose were measured during the treatment, and oxidative stress biomarkers, diabetes physiology, function and viability of cells were investigated at the end of the treatment in serum and pancreas tissues. Apoptosis of islets was examined by the flow cytometry. The high blood glucose level and significant weight loss resulting from diazinon were modified as a result of the application of the NPs. A significant recovery in oxidative stress markers, pro-insulin, insulin, C-peptide, adenosine diphosphate/adenosine triphosphate (ATP/ADP) ratio, caspase-3 and -9 activities and apoptosis–necrosis in the islets was observed. In conclusion, administration of CeO2 NPs or Y2O3 NPs only or their combination with suitable and defined dose will help to overcome the consequences from oxidant agents.

Protective effect of some plant oils on diazinon induced hepatorenal toxicity in male rats.

Environmental pollution and exposure to environmental pollutants are still some of the major global health issues. Pesticides have been linked to a wide range of health hazards. The toxicity of pesticides depends on several factors such as its chemical properties, doses, exposure period, exposure methods, gender, genetics, age, nutritional status and physiological case of exposed individuals. Medicinal plants, natural products and nutrition continue to play a central role in the healthcare system of large proportions of the world’s population. Alternative medicine plays an important role in health services around the world. The aim of this study was to investigate the effect of olive, sesame and black seed oils on hepatorenal toxicity induced by diazinon (DZN) in male rats. The experimental animals were divided into nine groups. The first group served as control. The second group was exposed to DZN. The third group was treated with olive oil and DZN. Rats of the fourth group were subjected to sesame oil and DZN. Rats of the fifth group were exposed to black seed oil and DZN. The sixth, seventh and eighth groups were supplemented with olive, sesame and black seed oils respectively. Rats of the ninth group were treated with corn oil. Levels of serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma glutamyl transferase, total bilirubin, creatinine, blood urea nitrogen and malondialdehyde were significantly increased in rats exposed to DZN. Moreover, levels of serum glutathione and superoxide dismutase were significantly decreased. Several histopathological changes were observed in the structures of liver and kidney due to DZN exposure. This study showed that these oils attenuated the physiological disturbances and histopathological alterations induced by DZN intoxication. Moreover, the antioxidant properties of these oils support the bioactive roles of its protective effects on DZN toxicity. This study therefore suggests that these oils could be used as preventive factors against the toxicity of DZN due to its antioxidant properties.

Improving function of rat pancreas, by using yttrium oxide nanoparticles in sub-acute diazinon exposure

Improving function of rat pancreas, by using yttrium oxide nanoparticles in sub-acute diazinon exposure

Sperm motility and morphology changes in rats exposed to cadmium and diazinon.

BackgroundHumans are ubiquitously exposed to multiple environmental contaminants. Consequences of combined action on the reproductive system remain unknown. This study aimed to assess single and joint effects of cadmium and diazinon exposure on sperm quality parameters.MethodsMale adult Wistar rats were randomized into 4 groups of ten animals each. Group A was used as a control, animals from group B were exposed to cadmium (30 mg/L), rats from group C were administered with diazinon (40 mg/L), and rats from group D were exposed simultaneously to cadmium (30 mg/L) and diazinon (40 mg/L) via drinking water for 90 days. Sperm morphology and motility were evaluated using a bright field microscope and a computer-assisted semen analysis.ResultsThe percentage of motile spermatozoa and morphologically normal sperm was markedly reduced in rats from the group B. Rats from the C group showed an increase in velocity parameters, amplitude of lateral head displacement, decrease in beat-cross frequency, and an increase in abnormal sperm morphology. Simultaneous coexposure to cadmium and diazinon increased distance and velocity parameters, and amplitude of lateral head displacement. Reductions were observed in straightness, linearity, wobble, and beat-cross frequency. The decreased normal sperm morphology rates were related to defects of the sperm tail.ConclusionsExposure to cadmium and diazinon at relatively low doses impairs sperm quality and can reduce male fertility. Cadmium and diazinon caused significant changes on sperm morphology with varying effects on motility patterns. These parameters were significantly higher in the group D as compared to the group C. The findings have important implications for reproductive risk assessment of combined exposures to multiple chemicals.

Prioritization of pesticides based on daily dietary exposure potential as determined from the SHEDS model

A major pathway for exposure to many pesticides is through diet. The objectives were to rank pesticides by comparing their calculated daily dietary exposure as determined by EPA's Stochastic Human Exposure and Dose Simulation (SHEDS) to single pesticides for different age groups to acceptable daily intakes (ADI), characterize pesticide trends in exposures over different time periods, and determine commodities contributing to pesticide exposures. SHEDS was applied, using Pesticide Data Program (PDP) (1991–2011) and pesticide usage data on crops from USDA combined with NHANES dietary consumption data, to generate exposure estimates by age group. ADI data collected from EPA, WHO, and other sources were used to rank pesticides based on relativeness of the dietary exposure potential to ADI by age groups. Sensitivity analysis provided trends in pesticide exposures. Within SHEDS, commodities contributing the majority of pesticides with greatest exposure potential were determined. The results indicated that the highest ranking pesticides were methamidophos and diazinon which exceeded 100% of the ADI. Sensitivity analysis indicated that exposure to methamidophos, diazinon, malathion, ethion and formetanate hydrochloride had a marked decrease from 1991–1999 to 2000–2011. Contributions analysis indicated that apples, mushroom, carrots, and lettuce contributed to diazinon exposure. Beans and pepper contributed to methamidophos exposure.

Mitigation of diazinon-induced cardiovascular and renal dysfunction by gallic acid.

Studies of the link between environmental pollutants and cardiovascular dysfunction, neglected for decades, have recently provided new insights into the pathology and consequences of these killers. In this study, rats were divided into four groups, each containing 10 rats. The rats in group one served as controls and were administered normal saline, whereas the rats in group two were orally gavaged with 3 mg/kg of diazinon (DZN) alone for twenty one consecutive days. The rats in groups 3 and 4 were administered respective 60 mg/kg and 120 mg/kg gallic acid (GA) in addition to DZN for twenty one consecutive days. Exposure of rats to diazinon significantly (p<0.05) reduced the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and reduced glutathione (GSH) content. Malondialdehyde, hydrogen peroxide (H2O2) and nitric oxide (NO) contents were also significantly (p<0.05) elevated following DZN exposure. DZN further caused a significant (p<0.05) decrease of heart rate and QT interval prolongation. Hematologic analysis revealed significant reduction (p<0.05) in packed cell volume (PCV), hemoglobin concentration (Hb), red blood cell (RBC) count, and total white blood cell count of rats administered only DZN. Observations in this study suggest a modulatory role of gallic acid in diazinon-induced anemia and associated cardiovascular dysfunction in rats. Treatment with gallic acid reversed the oxidative stress markers studied, increased the antioxidant defence system and reduced deleterious effects on hematological parameters in rats. Pathologic findings of the heart and kidney were also found to be lessened.

Sex-Specific Effects of Organophosphate Diazinon on the Gut Microbiome and Its Metabolic Functions.

Background:There is growing recognition of the significance of the gut microbiome to human health, and the association between a perturbed gut microbiome with human diseases has been established. Previous studies also show the role of environmental toxicants in perturbing the gut microbiome and its metabolic functions. The wide agricultural use of diazinon, an organophosphate insecticide, has raised serious environmental health concerns since it is a potent neurotoxicant. With studies demonstrating the presence of a microbiome–gut–brain axis, it is possible that gut microbiome perturbation may also contribute to diazinon toxicity.Objectives:We investigated the impact of diazinon exposure on the gut microbiome composition and its metabolic functions in C57BL/6 mice.Methods:We used a combination of 16S rRNA gene sequencing, metagenomics sequencing, and mass spectrometry–based metabolomics profiling in a mouse model to examine the functional impact of diazinon on the gut microbiome.Results:16S rRNA gene sequencing revealed that diazinon exposure significantly perturbed the gut microbiome, and metagenomic sequencing found that diazinon exposure altered the functional metagenome. Moreover, metabolomics profiling revealed an altered metabolic profile arising from exposure. Of particular significance, these changes were more pronounced for male mice than for female mice.Conclusions:Diazinon exposure perturbed the gut microbiome community structure, functional metagenome, and associated metabolic profiles in a sex-specific manner. These findings may provide novel insights regarding perturbations of the gut microbiome and its functions as a potential new mechanism contributing to diazinon neurotoxicity and, in particular, its sex-selective effects.Citation:Gao B, Bian X, Mahbub R, Lu K. 2017. Sex-specific effects of organophosphate diazinon on the gut microbiome and its metabolic functions. Environ Health Perspect 125:198–206; http://dx.doi.org/10.1289/EHP202

Effect of separate and combined exposure of selenium and diazinon on rat sperm motility by computer assisted semen analysis

Effects of selenium (Se) and diazinon (DZN) on sperm motility parameters in rats were investigated. Male rats received a separate dose of Se (2mgkg−1 b.w., intraperitoneally, 5mgL−1, per os in drinking water), diazinon (20mgkg−1 b.w., intraperitoneally, 40mgL−1, per os in drinking water), and in combination (Se+DZN) with the same dosage as in the separate administration. 36h an intraperitoneal (i.p.) and after 90days of per oral (p.o.) exposure, thirteen parameters of sperm motility were evaluated using a Computer Assisted Sperm Analyzer (CASA). Almost all the evaluated sperm motility parameters significantly decreased in Se p.o. exposed groups. In the Se i.p. group decrease was noted only in beat cross frequency (BCF) and progressive motility. Significant decline in the sperm motility, progressive motility, BCF and increase in amplitude of lateral head displacement (ALH) were recorded after DZN i.p. administration. In DZN p.o. group, significant increase in ALH, velocity average path (VAP) and curvilinear velocity (VCL) but decrease in progressive motility and BCF was detected. Se+DZN i.p. administration caused a significant decrease in motility, progressive motility and BCF. Per oral administration of Se+DZN decreased all motility parameters except LIN, WOB and ALH. Sperm abnormalities increased in all experimental conditions. Se and DZN negatively affected sperm structure and function in separate doses or in combination. No protective effect of Se was observed.

Mitigation of Diazinon‐induced cardiovascular and renal dysfunction by Gallic acid

The link between environmental pollutants and cardiovascular dysfunction had been neglected for the decades. However, new insights into the pathology and the consequences of these killers are being studied. In this study, rats were divided into four groups each containing 10 rats. Rats in group one served as controls and were administered normal saline, whereas rats in group two were orally gavaged with 3 mg/kg of Diazinon (DZN) alone for twenty one consecutive days. The rats in groups 3 and 4 were administered with 60 mg/kg and 120 mg/kg Gallic acid (GA) in addition to DZN for twenty one consecutive days. Exposure of rats to Diazinon significantly (p &lt;0.05) reduced the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione‐S‐transferase (GST) activities and reduced glutathione (GSH) content. Also, malondialdehyde, hydrogen peroxide (H2O2) generated and nitric oxide (NO) contents were also significantly (p &lt;0.05) elevated following DZN exposure. DZN also caused significant (p &lt;0.05) decreased heart rate and QT prolongation. Haematological analysis revealed significant reduction (p&lt; 0.05) in packed cell volume (PCV), Haemoglobin concentration (Hb), red blood cell (RBC) count, total white blood cell counts of rats administered only DZN. Observations in this study suggest a protective modulatory role for Gallic acid in Diazinon‐induced anaemia and associated cardiovascular dysfunction in rats. Treatment with Gallic acid reversed the aforementioned oxidative stress markers, increased antioxidant defence system and the deleterious effects on haematological parameters of rats. Pathology of the heart and kidney was also restored.

Strain-Related Differences on Response of Liver and Kidney Antioxidant Defense System in Two Rat Strains Following Diazinon Exposure

Background: Diazinon (DZN) is one of the most organophosphates that widely used in agriculture and ectoparasiticide formula- tions. Its extensive use as an eective pesticide was associated with the environmental deleterious eects on biological systems. Objectives: The aim of this study was to investigate the potency of DZN to aect serum biochemical parameters and the antioxidant defense system in the liver and kidney of two rat strains. Materials and Methods: In this experimental study, 30 female Wistar and 30 female Norway rats were randomly divided into con- trol and DZN groups. DZN group was divided into four subgroups: 25, 50, 100 and 200 mg/kg of DZN administered groups by i.p. injection. The parameters were evaluated after 24 hours. Results: At higher doses of DZN, superoxide dismutase, catalase, glutathione S-transferase and lactate dehydrogenase activities and glutathione (GSH) and malondialdehyde levels in liver and kidney of Wistar rats were higher than Norway rats. At these concentra- tions, DZN increased some serum biochemical indices such as liver enzymes activities and levels of urea, uric acid and creatinine in Wistar rat. Conclusions: DZN at higher doses alters the oxidant-antioxidant balance in liver and kidney of both rat strains and induces oxida- tive stress, which is associated with a depletion of GSH and increased lipid peroxidation. However, Wistar rats are found to be more sensitive to the toxicity of DZN compared to Norway rats. In addition, the eect of DZN on liver antioxidant system was more than

Mechanism for the acute effects of organophosphate pesticides on the adult 5-HT system

The neurotransmitter serotonin (5-HT) is involved in mood disorder aetiology and it has been reported that (organophosphate) OP exposure affects 5-HT turnover. The aim of this study was to elucidate the mechanism underlying OP effects on the adult 5-HT system. First, acute in vivo administration of the OP diazinon (0, 1.3, 13 or 39 mg/kg i.p.) to male Hooded Lister rats inhibited the activity of the cholinergic enzyme acetylcholinesterase in blood and in the hippocampus, dorsal raphe nucleus (DRN), striatum and prefrontal cortex. Diazinon-induced cholinesterase inhibition was greatest in the DRN, the brain's major source of 5-HT neurones. Second, acute in vivo diazinon exposure (0 or 39 mg/kg i.p.) increased the basal firing rate of DRN neurones measured ex vivo in brain slices. The excitatory responses of DRN neurones to α1-adrenoceptor or AMPA/kainate receptor activation were not affected by in vivo diazinon exposure but the inhibitory response to 5-HT was attenuated, indicating 5-HT1A autoreceptor down-regulation. Finally, direct application of the diazinon metabolite diazinon oxon to naive rat brain slices increased the firing rate of DRN 5-HT neurones, as did chlorpyrifos-oxon, indicating the effect was not unique to diazinon. The oxon-induced augmentation of firing was blocked by the nicotinic acetylcholine receptor antagonist mecamylamine and the AMPA/kainate glutamate receptor antagonist DNQX. Together these data indicate that 1) acute OP exposure inhibits DRN cholinesterase, leading to acetylcholine accumulation, 2) the acetylcholine activates nicotinic receptors on 5-HT neurones and also on glutamatergic neurones, thus releasing glutamate and activating 5-HT neuronal AMPA/kainate receptors 3) the increase in 5-HT neuronal activity, and resulting 5-HT release, may lead to 5-HT1A autoreceptor down-regulation. This mechanism may be involved in the reported increase in risk of developing anxiety and depression following occupational OP exposure.

Effects of vitamin E, selenium and vitamin C on various biomarkers following oxidative stress caused by diazinon exposure in rainbow trout

Biochemical parameters are appropriate biomarkers to assess the effects of pesticides on an aquatic ecosystem. Diazinon is an organophosphate pesticide whose metabolism in fish body produces reactive oxygen species that can cause oxidative stress. In this study, Oncorhynchus mykiss were allocated into four treatment groups (with three replicates): control; Diazinon; vitamin C + diazinon, and vitamin E,selenium + diazinon. Blood samples were obtained after two and four weeks and superoxide dismutase (SOD), catalase (CAT), total antioxidant capacity (TAC), and malondialdehyde (MDA) were measured. SOD activity was significantly lower in diazinon-exposed fish than in the control group. However, there were no differences between the two supplemented groups and the control group in this regard. CAT activity was significantly higher in all three diazinon-exposed groups compared to the control group. However vitamin E, selenium had the least difference with the control group. Maximum and minimum TAC were observed respectively in fish supplemented with vitamin E, selenium and those only exposed to diazinon. The diazinon group also had the highest MDA levels. The two supplemented groups and the control group had no significant differences in MDA levels. These findings highlighted the antioxidant effects of supplementation with vitamin E, selenium or vitamin C against free radical produced during the metabolism of diazinon. Meanwhile, the combination of vitamin E, selenium had higher antioxidant effects than vitamin C. Moreover, SOD, the first defensive barrier against superoxide radicals, and MDA, an index of cellular damage induced by hydroxyl radicals, are the most suitable indicators to assess the effects of diazinon.

Metabolomics reveals energetic impairments in Daphnia magna exposed to diazinon, malathion and bisphenol-A

1H nuclear magnetic resonance (NMR)-based metabolomics was used to study the response of Daphnia magna to increasing sub-lethal concentrations of either an organophosphate (diazinon or malathion) or bisphenol-A (BPA). Principal component analysis (PCA) of 1H NMR spectra were used to screen metabolome changes after 48h of contaminant exposure. The PCA scores plots showed that diazinon exposures resulted in aberrant metabolomic profiles at all exposure concentrations tested (0.009–0.135 μg/L), while for malathion the second lowest (0.08μg/L) and two highest exposure concentrations (0.32μg/L and 0.47μg/L) caused significant shifts from the control. Individual metabolite changes for both organophosphates indicated that the response to increasing exposure was non-linear and described perturbations in the metabolome that were characteristic of the severity of exposure. For example, intermediate concentrations of diazinon (0.045μg/L and 0.09μg/L) and malathion (0.08μg/L) elicited a decrease in amino acids such as leucine, valine, arginine, glycine, lysine, glutamate, glutamine, phenylalanine and tyrosine, with concurrent increases in glucose and lactate, suggesting a mobilization of energy resources to combat stress. At the highest exposure concentrations for both organophosphates there was evidence of a cessation in metabolic activity, where the same amino acids increased and glucose and lactate decreased, suggesting a slowdown in protein synthesis and depletion of energy stocks. This demonstrated a similar response in the metabolome between two organophosphates but also that intermediate and severe stress levels could be differentiated by changes in the metabolome. For BPA exposures, the PCA scores plot showed a significant change in metabolome at 0.1mg/L, 1.4mg/L and 2.1mg/L of exposure. Individual metabolite changes from 0.7 to 2.1mg/L of BPA exposure showed increases in amino acids such as alanine, valine, isoleucine, leucine, arginine, phenylalanine and tyrosine. These metabolite changes were correlated with decreases in glucose and lactate. This pattern of response was also seen in the highest organophosphate exposures and suggested a generalized stress response that could be related to altered energy dynamics in D. magna. Through studying increasing exposure responses, we have demonstrated the ability of metabolomics to identify discrete differences between intermediate and severe stress, and also to characterize how systemic stress is manifested in the metabolome.