Outcomes of elderly patients with organophosphate intoxication.

This study analysed the clinical patterns and outcomes of elderly patients with organophosphate intoxication. A total of 71 elderly patients with organophosphate poisoning were seen between 2008 and 2017. Patients were stratified into two subgroups: survivors (n = 57) or nonsurvivors (n = 14). Chlorpyrifos accounted for 33.8% of the cases, followed by methamidophos (12.7%) and mevinphos (11.3%). Mood, adjustment and psychotic disorder were noted in 39.4%, 33.8% and 2.8% of patients, respectively. All patients were treated with atropine and pralidoxime therapies. Acute cholinergic crisis developed in all cases (100.0%). The complications included respiratory failure (52.1%), aspiration pneumonia (50.7%), acute kidney injury (43.7%), severe consciousness disturbance (25.4%), shock (14.1%) and seizures (4.2%). Some patients also developed intermediate syndrome (15.5%) and delayed neuropathy (4.2%). The nonsurvivors suffered higher rates of hypotension (P < 0.001), shock (P < 0.001) and kidney injury (P = 0.001) than survivors did. Kaplan-Meier analysis indicated that patients with shock suffered lower cumulative survival than did patients without shock (log-rank test, P < 0.001). In a multivariate-Cox-regression model, shock was a significant predictor of mortality after intoxication (odds ratio 18.182, 95% confidence interval 2.045-166.667, P = 0.009). The mortality rate was 19.7%. Acute cholinergic crisis, intermediate syndrome, and delayed neuropathy developed in 100.0%, 15.5%, and 4.2% of patients, respectively.

In Vitro Antioxidant Activity of Litsea martabanica Root Extract and Its Hepatoprotective Effect on Chlorpyrifos-Induced Toxicity in Rats.

In Thailand, people in the highland communities whose occupational exposure to pesticides used the root of Litsea martabanica as a detoxifying agent. However, the scientific data to support the traditional use of this plant are insufficient. This study aimed to evaluate the antioxidant activity and anti-pesticide potential of L. martabanica root extract. Antioxidant properties were investigated by 2,2'-diphenyl-1-picrylhydrazyl (DPPH) assay, superoxide radicals scavenging assay, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assay, ferric reducing antioxidant power (FRAP), and total phenolic content determination. In all assays, L. martabanica extracts and their fractions exhibited high antioxidant activities differently. The water extract is traditionally used as a detoxifying agent. Therefore, it was chosen for in vivo experiments. The rats received the extract in a way that mimics the traditional methods of tribal communities followed by chlorpyrifos for 16 days. The results showed that acetylcholinesterase activity decreases in pesticide-exposed rats. Treatment with the extract caused increasing acetylcholinesterase activity in the rats. Therefore, L. martabanica extract may potentially be used as a detoxifying agent, especially for the chlorpyrifos pesticide. The antioxidant properties of L. martabanica may provide a beneficial effect by protecting liver cells from damage caused by free radicals. Histopathology results revealed no liver cell necrosis and showed the regeneration of liver cells in the treatment group. L. martabanica extract did not cause changes in behavior, liver weight, hematological and biochemical profiles of the rats.

Quercetin ameliorates the hepatic apoptosis of foetal rats induced by in utero exposure to fenitrothion via the transcriptional regulation of paraoxonase-1 and apoptosis-related genes.

BACKGROUND & PURPOSE: Exposure to organophosphorus during different phases of pregnancy induces many adverse impacts on the developing foetuses due to their immature detoxification system. We have estimated the potential amelioration role of quercetin against hepatic injury-induced apoptosis in rat foetuses following gestational exposure to fenitrothion and probable involvement of paraoxonase-1. METHODS: Forty pregnant rats were allocated into four groups; the first one kept as control, the second intubated with quercetin (100 mg/kg), the third orally administrated fenitrothion (4.62 mg/kg) and the last group received quercetin two hours before fenitrothion intoxication. RESULTS: Fenitrothion significantly elevated the foetal hepatic levels of thiobarbituric acid reactive substances, protein carbonyl, and nitric oxide, but it reduced the enzymatic activities of glutathione-S-transferase, superoxide dismutase, catalase, and acetylcholinesterase. Furthermore, fenitrothion provoked many histopathological changes in the foetal liver and markedly up-regulated the mRNA gene expression of p53, caspase-9 along with elevation in the immunoreactivity of Bax and caspase-3, but it down-regulated the expression level of paraoxonase-1. Remarkably, quercetin co-treatment successfully ameliorated the hepatic oxidative injury and apoptosis prompted by fenitrothion. CONCLUSIONS: Dietary supplements with quercetin can be used to reduce the risk from organophosphorus exposure probably through paraoxonase-1 up-regulation and enhancement of the cellular antioxidant system.

Nano-curcumin versus curcumin in amelioration of deltamethrin-induced hippocampal damage.

We aimed to prove that oxidative stress is the main mechanism responsible for hippocampal neurotoxicity induced by deltamethrin (DLM). The protective role of curcumin (CMN) and nano-curcumin (NCMN) over this toxicity was studied. The rats were categorized into four groups: control, DLM, CMN and NCMN. The study continued for 30 days. Hippocampus was processed for histological, biochemical and immunohistochemical studies. Caspase-3, glial fibrillar acidic protein (GFAP), acetylcholinesterase (AChE), malondialdehyde (MDA), glutathione (GSH), catalase (CAT) and superoxide dismutase (SOD) were measured for DLM-induced oxidative stress (increased MDA by 354%/decreased GSH by 61%, SOD by 61%, CAT 57%). Oxidative stress induced apoptosis of hippocampal neurons through increasing Nrf2, gamma-glutamyl cysteine synthetase heavy subunit (GCS-HS) and light subunit (GCS-LS) and decreasing AChE. It increases the activity of astrocytes through increasing GFAP. Finally, oxidative stress has a bad impaction on cognitive function. Improvement of oxidative stress was observed with use of CMN and NCMN (decrease of MDA/increase of GSH, SOD, CAT). The level of Nrf2, GCS-HS and GCS-LS decreased, while AChE, GFAP increased. Improvement of cognitive function was observed in both groups. In conclusion, oxidative stress is the common mechanism responsible for DLM-induced hippocampal neurotoxicity. It exerts apoptosis of hippocampal neurons through increasing Nrf2, HS-GCS, LS-GCS and decreasing AChE. In addition, it activates astrocytes through increasing expression of GFAP. The protective role of CMN and CMMN is related to their potent antioxidant effect. Much improvement has been detected with NCMN as compared to CMN.

Oxidative stress-mediated genotoxicity of malathion in human lymphocytes.

Applying the single-cell gel electrophoresis (comet) assay, we show that the widely used organophosphorus pesticide malathion is cytotoxic, genotoxic, and induces oxidative stress in human lymphocytes.

Diphenyl diselenide abrogates chlorpyrifos-induced hypothalamic-pituitary-testicular axis impairment in rats.

Exposure to pesticide chlorpyrifos (CPF) has been implicated in reproductive deficits in both humans and animals. Diphenyl diselenide (DPDS) is an organoselenium compound widely reported to elicit potent pharmacological activities in several chemically-induced toxicity and disease models. However, there is paucity of scientific information on the influence of DPDS on CPF-induced reproductive dysfunction. The present study investigated the influence of DPDS on CPF-induced functional changes along the hypothalamic-pituitary- testicular axis in rats. CPF was administered alone at 5 mg/kg body weight or orally co-treated with DPDS at 2.5 and 5 mg/kg body weight for 35 consecutive days. Results showed that DPDS co-treatment significantly (p < 0.05) abrogated CPF-induced oxidative stress by increasing the antioxidant enzymes activities and glutathione content, decreasing the hydrogen peroxide and lipid peroxidation levels in the hypothalamus, testes and epididymis of the treated rats. Moreover, DPDS co-treatment significantly ameliorated CPF-induced histological alterations in the hypothalamus, testes and epididymis of the treated rats. Besides, the significant augmentation of luteinizing hormone, follicle-stimulating hormone and testosterone levels as well as the testicular activities of acid phosphatase, alkaline phosphatase and lactate dehydrogenase by DPDS was accompanied by an increase in sperm quality and quantity in the treated rats. Taken together, DPDS abrogates CPF mediated toxicity along the hypothalamic-pituitary-testicular axis in rats via inhibition of lipid peroxidation, enhancement of antioxidant enzymes activities and testicular function. Thus, DPDS may be a possible chemoprotective drug candidate against CPF-induced male reproductive deficits in humans.

Synthesis, Biological Evaluation, and Docking Studies of Novel Bisquaternary Aldoxime Reactivators on Acetylcholinesterase and Butyrylcholinesterase Inhibited by Paraoxon.

Nerve agents and oxon forms of organophosphorus pesticides act as strong irreversible inhibitors of two cholinesterases in the human body: acetylcholinesterase (AChE; EC 3.1.1.7) and butyrylcholinesterase (BChE; EC 3.1.1.8), and are therefore highly toxic compounds. For the recovery of inhibited AChE, antidotes from the group of pyridinium or bispyridinium aldoxime reactivators (pralidoxime, obidoxime, HI-6) are used in combination with anticholinergics and anticonvulsives. Therapeutic efficacy of reactivators (called "oximes") depends on their chemical structure and also the type of organophosphorus inhibitor. Three novel oximes (K131, K142, K153) with an oxime group in position four of the pyridinium ring were designed and then tested for their potency to reactivate human (Homo sapiens sapiens) AChE (HssACHE) and BChE (HssBChE) inhibited by the pesticide paraoxon (diethyl 4-nitrophenyl phosphate). According to the obtained results, none of the prepared oximes were able to satisfactorily reactivate paraoxon-inhibited cholinesterases. On the contrary, extraordinary activity of obidoxime in the case of paraoxon-inhibited HssAChE reactivation was confirmed. Additional docking studies pointed to possible explanations for these results.

Effect of Tunceli garlic on some immunological parameters in Cyprinus carpio exposed to chlorpyrifos.

In this study, the effect of Tunceli garlic (Allium tuncelianium) on hemoglobin (Hb) level, oxidative radical production of neutrophils (Nitoblue tetrazolium assay-NBT activity) and total immunoglobulin (TI) content in carp (Cyprinus carpio) exposed to chlorpyrifos (CPF)  was investigated. The 96 hour LC50 value of CPF on C. carpio was calculated to as 0.230 mg/L. The fishes were exposed to sublethal concentration of chlorpyrifos (1/8 of LC50 value: 0.029 mg/L), and Tunceli garlic (20 and 40 g/kg diet) was simultaneously administered for 21 days. Blood samples were taken from the fishes at 7, 14 and 21 days and analysed to determine the Hb levels, the NBT activity and the TI content. There was a significant decrease in the Hb level, the NBT activity and the TI content of CPF-treated fish. However, Tunceli garlic reversed the Hb level, the NBT activity and the TI content. In conclusion, this study demonstrated that CPF had a negative effect on the immunological values of the fish. The simultaneous administration of Tunceli garlic was neutralised CPF-induced toxicity.

Polyphenol-Rich Fraction of Parquetina nigrescens Mitigates Dichlorvos-Induced Cardiorenal Dysfunction Through Reduction in Cardiac Nitrotyrosine and Renal p38 Expressions in Wistar Rats.

Parquetina nigrescens is commonly used to treat diseases in humans and animals in developing countries, including Nigeria. This study evaluates the effects of its polyphenol-rich fraction (prf) on dichlorvos-induced cardio- and renal toxicity. There were several factors assessed during this study, including cardiac and renal markers, serum myeloperoxidase and xanthine oxidase, and electrocardiograph (ECG) changes. The changes in electrocardiograph (ECG) were recorded. Immunohistochemistry of cardiac and renal p38 and nitrotyrosine was determined. Dichlorvos exposure caused a significant decrease in L-glutathione (reduced glutathione) and other antioxidant enzymes with increases in malondialdehyde, myeloperoxidase, advanced oxidation protein products, and protein carbonyl levels. It also brought about alterations in microanatomy of the heart and kidneys accompanied by increases in serum creatinine and urea levels. Exposure to dichlorvos induced prolonged QRS interval and shortened QT durations in rats. Immunohistochemistry revealed lower expressions of cardiac nitrotyrosine and renal p38 (mitogen-activated protein kinase; MAPK) in rats treated with prf of P. nigrescens. Combining all, prf of P. nigrescens demonstrated antioxidant as well as protective properties in the heart and kidneys of rats exposed to dichlorvos. It ameliorated dichlorvos-induced cardio- and nephrotoxicity giving credence to its use in ethnomedicine.

Neuroprotective potential of crocin against malathion-induced motor deficit and neurochemical alterations in rats.

In several epidemiological studies, an association between pesticide exposure and the incidence of Parkinson's disease (PD) has been reported. Increasing evidence showed that oxidative stress plays an important role in the pathogenesis of PD. The present study investigated the preventive effect of crocin, saffron active components, on malathion (an organophosphate pesticide (OP))-induced Parkinson-like behaviors in rat. Rats were divided into eight groups: control (normal saline), malathion (100 mg/kg/day, i.p), crocin (10, 20, or 40 mg/kg/day, i.p) plus malathion, levodopa (10 mg/kg/day, i.p) plus malathion, crocin (40 mg/kg/day, i.p), and PEG (vehicle of levodopa) groups. Treatments were continued for 28 days. The neurobehavioral tests which include open field, rotarod and catalepsy were performed on day 28. The activity of acetylcholinesterase (AChE) in serum, the levels of malondialdehyde (MDA), reduced glutathione (GSH), TNF-α, and IL-6 in striatum at the end of treatments were evaluated. Results showed that malathion induced neurobehavioral impairments together with elevation of MDA, TNF-α and IL-6 levels, reduction of GSH, and AChE activity. Crocin (10, 20, and 40 mg/kg) improved neurobehavioral impairments induced by malathion but not AChE activity. Crocin (10, 20, and 40 mg/kg) or levodopa plus malathion decreased MDA and increased GSH. Also crocin (10 mg/kg) decreased TNF-α and IL-6 levels in striatum. In summary, subchronic malathion exposure induced Parkinson-like behavior in rat. Crocin exhibited protective effects against malathion-induced Parkinson-like behavior through reducing lipid peroxidation, improvement of motor deficit and anti-inflammatory effects.

Species specific RNA A-to-I editing of mosquito RDL modulates GABA potency and influences agonistic, potentiating and antagonistic actions of ivermectin.

The insect GABA receptor, RDL, is the target of several classes of pesticides. The peptide sequences of RDL are generally highly conserved between diverse insects. However, RNA A-to-I editing can effectively alter amino acid residues of RDL in a species specific manner, which can affect the potency of GABA and possibly insecticides. We report here that RNA A-to-I editing alters the gene products of Rdl in three mosquito disease vectors, recoding five amino acid residues in RDL of Aedes aegypti and six residues in RDLs of Anopheles gambiae and Culex pipiens, which is the highest extent of editing in RDL observed to date. Analysis of An. gambiae Rdl cDNA sequences identified 24 editing isoforms demonstrating a considerable increase in gene product diversity. RNA editing influenced the potency of the neurotransmitter, GABA, on An. gambiae RDL editing isoforms expressed in Xenopus laevis oocytes, as demonstrated by EC50s ranging from 5 ± 1 to 246 ± 41 µM. Fipronil showed similar potency on different editing isoforms, with IC50s ranging from 0.18 ± 0.08 to 0.43 ± 0.09 µM. In contrast, editing of An. gambiae RDL affected the activating, potentiating and inhibiting actions of ivermectin. For example, ivermectin potentiated currents induced by GABA at the EC20 concentration in the unedited isoform but not in the fully edited variant. Editing of a residue in the first transmembrane domain or the cys-loop influenced this potentiation, highlighting residues involved in the allosteric mechanisms of cys-loop ligand-gated ion channels. Understanding the interactions of ivermectin with molecular targets may have relevance to mosquito control in areas where people are administered with ivermectin to treat parasitic diseases.

Protective effect of α-lipoic acid against α-cypermethrin-induced changes in rat cerebellum.

Alfa cypermethrin is a pyrethroids extensively used as ectoparasiticide in domestic animals, insecticidal spray on cotton, vegetables and other crops and to kill cockroaches, fleas and termites in house and other buildings. Previous studies have shown the adverse effect of α -cypermethrin on brain. This study was planned to evaluate the possible role of α-lipoic acid in α -cypermethrin induced toxicity in brain of male albino rats. Rats were divided into four groups. The control, α-cypermethrin, α-lipoic acid and α -cypermethrin plus α-lipoic acid treated groups. The duration of the experiment was four weeks. Our results showed that the administration of α-cypermethrin caused a significant decreased in γ- aminobutyric acid level, acetylcholinesterase, catalase, superoxide dismutase activities and increase in lipid peroxidation in cerebellum. Furthermore, the co-administration of α-lipoic acid mitigates the toxicity of α-cypermethrin by partially normalizing the biochemical parameters. The biochemical observations were supported by histopathological examinations. The findings of this investigation suggest that α-lipoic acid may play a protective role against α-cypermethrin induced toxicity in cerebellum of treated rats.

A P-glycoprotein gene serves as a component of the protective mechanisms against 2-tridecanone and abamectin in Helicoverpa armigera.

P-glycoprotein (P-gp) exists in animals, fungi and bacteria and likely evolved as a defense mechanism against harmful substances. Here a cDNA (4054bp) encoding a putative P-glycoprotein gene from Helicoverpa armigera was cloned and named HaPgp1. This putative HaPgp1 sequence encoded a protein of 1253 amino acids with a molecular mass of approximately 137kDa. qPCR analyses demonstrated that the expression of HaPgp1 was significantly higher in 4th instar larvae when compared to other developmental stages. HaPgp1 transcripts were more abundant in the head and fat bodies than in other tissues. Compared with the control, the expression of HaPgp1 reach a peak at 12h after the treatment by 2-tridecanone in all tissues. However, the expression of HaPgp1 increased from 12h to 48h after treatment with abamectin in all tissues. Immunohistochemistry analyses also verified that 2-tridecanone and abamectin can induce the increase of HaPgp1 expression. RNAi of HaPgp1 significantly raised the mortality rate of larvae treated by 2-tridecanone and abamectin, as compared to control larvae fed with GFP dsRNA. These results illustrate the possible involvement of HaPgp1 as a component of the protective mechanisms to plant secondary chemicals such as 2-tridecanone and to certain classes of insecticides, like abamectin.

24-epibrassinolide stimulates imidacloprid detoxification by modulating the gene expression of Brassica juncea L.

BACKGROUND: Pesticides cause oxidative stress to plants and their residues persist in plant parts, which are a major concern for the environment as well as human health. Brassinosteroids (BRs) are known to protect plants from abiotic stress conditions including pesticide toxicity. The present study demonstrated the effects of seed-soaking with 24-epibrassinolide (EBR) on physiological responses of 10-day old Brassica juncea seedlings grown under imidacloprid (IMI) toxicity. RESULTS: In the seedlings raised from EBR-treated seeds and grown under IMI toxicity, the contents of hydrogen peroxide (H2O2) and superoxide anion (O.2-) were decreased, accompanied by enhanced activities of superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), glutathione-S-transferase (GST), guaiacol peroxidase (POD) and the content of glutathione (GSH). As compared to controls, the gene expressions of SOD, CAT, GR, POD, NADH (NADH-ubiquinone oxidoreductase), CXE (carboxylesterase), GSH-S (glutathione synthase), GSH-T (glutathione transporter-1), P450 (cytochrome P450 monooxygenase) and GST1-3,5-6 were enhanced in the seedlings raised from EBR-treated seeds and grown in IMI supplemented substratum. However, expression of RBO (respiratory burst oxidase, the gene responsible for H2O2 production) was decreased in seedlings raised from EBR treated seeds and grown under IMI toxicity. Further, the EBR seed treatment decreased IMI residues by more than 38% in B. juncea seedlings. CONCLUSIONS: The present study revealed that EBR seed soaking can efficiently reduce oxidative stress and IMI residues by modulating the gene expression of B. juncea under IMI stress. In conclusion, exogenous EBR application can protect plants from pesticide phytotoxicity.

Mode of Action of the Natural Insecticide, Decaleside Involves Sodium Pump Inhibition.

Decalesides are a new class of natural insecticides which are toxic to insects by contact via the tarsal gustatory chemosensilla. The symptoms of their toxicity to insects and the rapid knockdown effect suggest neurotoxic action, but the precise mode of action and the molecular targets for decaleside action are not known. We have presented experimental evidence for the involvement of sodium pump inhibition in the insecticidal action of decaleside in the cockroach and housefly. The knockdown effect of decaleside is concomitant with the in vivo inhibition of Na+, K+ -ATPase in the head and thorax. The lack of insecticidal action by experimental ablation of tarsi or blocking the tarsal sites with paraffin correlated with lack of inhibition of Na+- K+ ATPase in vivo. Maltotriose, a trisaccharide, partially rescued the toxic action of decaleside as well as inhibition of the enzyme, suggesting the possible involvement of gustatory sugar receptors. In vitro studies with crude insect enzyme preparation and purified porcine Na+, K+ -ATPase showed that decaleside competitively inhibited the enzyme involving the ATP binding site. Our study shows that the insecticidal action of decaleside via the tarsal gustatory sites is causally linked to the inhibition of sodium pump which represents a unique mode of action. The precise target(s) for decaleside in the tarsal chemosensilla and the pathway linked to inhibition of sodium pump and the insecticidal action remain to be understood.

A simple and highly effective catalytic nanozyme scavenger for organophosphorus neurotoxins.

A simple and highly efficient catalytic scavenger of poisonous organophosphorus compounds, based on organophosphorus hydrolase (OPH, EC 3.1.8.1), is produced in aqueous solution by electrostatic coupling of the hexahistidine tagged OPH (His6-OPH) and poly(ethylene glycol)-b-poly(l-glutamic acid) diblock copolymer. The resulting polyion complex, termed nano-OPH, has a spherical morphology and a diameter from 25nm to 100nm. Incorporation of His6-OPH in nano-OPH preserves catalytic activity and increases stability of the enzyme allowing its storage in aqueous solution for over a year. It also decreases the immune and inflammatory responses to His6-OPH in vivo as determined by anti-OPH IgG and cytokines formation in Sprague Dawley rats and Balb/c mice, respectively. The nano-OPH pharmacokinetic parameters are improved compared to the naked enzyme suggesting longer blood circulation after intravenous (iv) administrations in rats. Moreover, nano-OPH is bioavailable after intramuscular (im), intraperitoneal (ip) and even transbuccal (tb) administration, and has shown ability to protect animals from exposure to a pesticide, paraoxon and a warfare agent, VX. In particular, a complete protection against the lethal doses of paraoxon was observed with nano-OPH administered iv and ip as much as 17h, im 5.5h and tb 2h before the intoxication. Further evaluation of nano-OPH as a catalytic bioscavenger countermeasure against organophosphorus chemical warfare agents and pesticides is warranted.

PPAR-γ activation attenuates deltamethrin-induced apoptosis by regulating cytosolic PINK1 and inhibiting mitochondrial dysfunction.

Central events in the mitochondrial-dependent cell death pathway include the disruption of mitochondrial membrane potential, which causes the release of apoptogenic molecules leading to cell death. Based on the cytotoxic mechanism of deltamethrin (DLM), we examined the neuroprotective mechanisms of rosiglitazone (RGZ), which is against DLM-induced neuronal cell death. In this study, we found that DLM induces apoptosis in SH-SY5Y cells as demonstrated by the activation of caspase-3 and nuclear condensation. In addition, neuronal cell death in response to DLM was due to mitochondrial dependent-apoptosis pathways since DLM increased cytochrome c release into the cytosol and activated caspase-9. DLM exposure reduced PINK1 expression, and pretreatment with RGZ significantly reduced cytochrome c release and caspase-9 activation. RGZ also attenuated the reduction of complex I activity, mitochondrial membrane potential, and ATP levels. Pretreatment with RGZ significantly enhanced PINK1 expression in DLM-exposed cells. In addition, RGZ increased cytosolic PINK1 by inhibiting mitochondrial translocation of PINK1. Interestingly, RGZ fails to rescue DLM-induced mitochondrial dysfunction both in PINK1 knockdown and PPAR-γ antagonist treated cells. Results from this study suggest that RGZ exerts anti-apoptotic effects against DLM-induced cytotoxicity by attenuation of mitochondrial dysfunction through cytosolic PINK1-dependent signaling pathways.

Synergistic ameliorative effects of sesame oil and alpha-lipoic acid against subacute diazinon toxicity in rats: hematological, biochemical, and antioxidant studies.

Diazinon (DZN) is a common organophosphorus insecticide extensively used for agriculture and veterinary purposes. DZN toxicity is not limited to insects; it also induces harmful effects in mammals and birds. Our experiment evaluated the protective and antioxidant potential of sesame oil (SO) and (or) alpha-lipoic acid (ALA) against DZN toxicity in male Wistar albino rats. DZN-treated animals exhibited macrocytic hypochromic anemia and significant increases in serum biochemical parameters related to liver injury, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), γ-glutamyl transferase (γGT), cholesterol, and triglycerides. They also had elevated levels of markers related to cardiac injury, such as lactate dehydrogenase (LDH) and creatine phosphokinase (CPK), and increased biomarkers of renal injury, urea and creatinine. DZN also increased hepatic, renal, and cardiac lipid peroxidation and decreased antioxidant biomarker levels. SO and (or) ALA supplementation ameliorated the deleterious effects of DZN intoxication. Treatment improved hematology and serum parameters, enhanced endogenous antioxidant status, and reduced lipid peroxidation. Importantly, they exerted synergistic hepatoprotective, nephroprotective, and cardioprotective effects. Our findings demonstrate that SO and (or) ALA supplementation can alleviate the toxic effects of DZN via their potent antioxidant and free radical-scavenging activities.

Quercetin mitigates fenitrothion-induced testicular toxicity in rats.

Fenitrothion (FNT) is a widely used organophosphorus pesticide in agriculture. Quercetin (QR), a plant-derived flavonoid, has a free radical scavenging property. This study investigated the protective effect of QR on FNT-induced testicular toxicity in rats. Twenty-four male rats were divided into four groups. Group I (control) received normal saline. Group II was administered QR at the dose of 50 mg kg(-1) b.wt. Group III was orally administered FNT (20 mg kg(-1) b.wt). Group IV was gavaged FNT and QR together at the same doses. All administrations were performed daily by gavage and maintained for 70 days. Sperm parameters and histopathological changes in testes were investigated. Serum testosterone and luteinising hormone were estimated using radioimmunoassay kits. In testes, expressions of steroidogenic genes (3ß-hydroxysteroid dehydrogenase type 6, 17 ß-hydroxysteroid dehydrogenase type 3 and steroidogenic factor-1) and oxidative stress genes (catalase and superoxide dismutase) were determined using real-time PCR. FNT administration caused significant decreases in sperm count, motility and hormonal levels, a significant increase in abnormal sperm morphology and a significant down-regulation of steroidogenic and antioxidant genes in the testis. However, QR administration ameliorated FNT-induced toxic effects. Our results concluded that QR effectively mitigated testicular damage induced by FNT in rats.

Oxidative Stress, Cytotoxicity, and Genotoxicity Induced by Methyl Parathion in Human Gingival Fibroblasts: Protective Role of Epigallocatechin-3-Gallate.

Organophosphorous (OP) compounds are pesticides frequently released into the environment because of extensive use in agriculture. Among these, methyl parathion (mPT) recently received attention as a consequence of illegal use. The predominant route of human exposure to mPT is via inhalation, but inadvertent consumption of contaminated foods and water may also occur. The goal of this study was to investigate the in vitro effects of mPT on cells in the oral cavity and evaluate the potential protective role of epigallocathechin-3-gallate (EGCG) on these effects. Human gingival fibroblasts (HGF) were exposed to 10, 50, or 100 µ g/ml mPT for 24 h and assessed for oxidative stress, as evidenced by reactive generation of oxygen species (ROS), induction of apoptotic cell death, DNA damage (comet assay and cytochinesis-block micronucleus test), and nitric oxide (NO) production. The results showed that mPT produced significant oxidative stress, cytotoxicity, and genotoxicity and increased NO levels through stimulation of inducible NO synthase expression. Finally, data demonstrated that EGCG (10, 25, or 50 µ M) was able to inhibit the pesticide-induced effects on all parameters studied. Data indicate that cytotoxic and genotoxic effects may be associated with oxidative stress induced by mPT observed in HGF cultures and that EGCG plays a protective role via antioxidant activities.