Nonthiol ACE inhibitors, enalapril and lisinopril are unable to protect mitochondrial toxicity due to paraquat

Angiotensin-converting enzyme inhibitors (ACEi) were shown to ameliorate endothelial dysfunction in various human diseases and some of these inhibitors have been reported to enhance antioxidant defenses. The objective of the present study was to shown the abilities of enalapril and lisinopril as two nonthiol ACEi on mitochondrial toxicity due to paraquat. In this study, mitochondrial isolation from rat liver was divided into six groups. Group 1 was considered as control, group 2 received paraquat (5 mM), group 3 received enalapril (0.25 mM), group 4 received lisinopril (0.01 mM), group 5 received paraquat (5 mM) + enalapril (0.25 mM), and group 6 received paraquat(5 mM) + lisinopril (0.01 mM). Viability, lipid peroxidation, catalase activity, GSH (reduced glutathione) and GSSG (oxidized glutathione) concentrations were also determined. Simultaneous treatment of mitochondria with enalapril (0.25 mM) + paraquat (5 mM) and lisinopril (0.0.01 mM) + paraquat (5 mM) did not significantly ameliorate the mitochondrial toxicity induced by paraquat (5 mM) alone (p > 0.05). However, the nonthiol ACEi, enalapril showed to partially improve target of lipid peroxidation due to paraquat. In conclusion, nonthiol ACEi treatment did not improve the increased oxidative stress and the decreased antioxidant mechanisms.     

Protection by cAMP and cGMP phosphodiesterase inhibitors of diazinon-induced hyperglycemia and oxidative/nitrosative stress in rat Langerhans islets cells: Molecular evidence for involvement of non-cholinergic mechanisms

The objective of this study was to study the effects of acute administration of diazinon alone or in combination with two phosphodiesterase (PDE) inhibitors with selectivity to cAMP and cGMP (theophylline and sildenafil, respectively) on oxidative/nitrosative stress biomarkers, including nitric oxide (NO), lipid peroxides (TBARS), total antioxidant power (TAP), and concentration of tumor necrosis factor (TNF-α) in isolated Langerhans islets, plasma glucose and insulin levels, and the activity of plasma cholinesterase (ChE). Examination by different doses of diazinon (15, 30, and 60 mg/kg) in single administration lead us to choose diazinon (30 mg/kg) in combination therapies. Theophylline and sildenafil were used at doses of 25 and 5 mg/kg, respectively. In all diazinon-treated groups, plasma ChE activity and plasma insulin level were significantly decreased and plasma glucose concentration and Langerhans islets TNF-α, TBARS, and NO levels were significantly increased in comparison to controls. The TAP did not change in comparison to control. In combination therapy, both theophylline and sildenafil restored diazinon-induced changes in plasma glucose concentration, Langerhans islets TNF-α, NO, and TBARS concentrations but Langerhans islets TAP, plasma insulin, and ChE levels. It is concluded that diazinon stimulates oxidative/nitrosative stress in Langerhans islets that results in hyperglycemia due to insufficiency of insulin. Altered glucagons/insulin ratio, activated hepatic glucose production/release, and insulin resistance are possible mechanisms. The protective effects of cAMP and cGMP PDE inhibitors in restoration of diazinon-induced oxidative/nitrosative stress and hyperglycemia stress back to their antioxidant potentials that seem to be independent of ChE inhibition.     

Cypermethrin-induced alterations in vital physiological parameters and oxidative balance in Caenorhabditis elegans

Cypermethrin belongs to the class of synthetic pyrethroids, which are being widely used as an insecticides in agricultural practices. The toxicity of cypermethrin is well studied in Drosophila melanogaster, fish, rats, mice, and is reported to cause neurotoxicity and oxidative stress during its metabolism. In this study, we evaluated the biological consequences of 4 h exposure to cypermethrin at sublethal concentrations (1, 5 and 15 mM) in Caenorhabditis elegans on physiological parameters such as egg laying, brood size, feeding and lifespan and oxidative stress parameters such as ROS, hydrogen peroxide levels, protein carbonyl, enzymatic antioxidants and glutathione levels. There was a significant and dose-dependent decrease in brood size (18-53%), egg laying (54-67%), feeding (29-58%) and marked decrease in lifespan (20%) at 15 mM of cypermethrin. Increase in levels of oxidative markers such as ROS (21-56%), intracellular hydrogen peroxide (17-62%), protein carbonyl (8-29%) and alteration in the activity of enzymatic antioxidants as well as depletion of glutathione (13-38%) were also observed. Our study offers evidence to show that cypermethrin induces significant oxidative stress in C. elegans and alters several physiological parameters in these worms, which can lead to impaired functioning, and survival of these worms.     

Allelochemical ethyl 2-methyl acetoacetate (EMA) induces oxidative damage and antioxidant responses in Phaeodactylum tricornutum

Ethyl 2-methyl acetoacetate (EMA) is a novel allelochemical exhibiting inhibitory effects on the growth of marine unicellular alga Phaeodactylum tricornutum (P. tricornutum). Oxidative damage and antioxidant responses in P. tricornutum were investigated to elucidate the mechanism involved in EMA inhibition on algal growth. The increase in reactive oxygen species (ROS) levels and malondialdehyde (MDA) contents following exposure to EMA suggested that alga was suffered from oxidative stress and severely damaged. The decrease in cell activity and cellular inclusions suggested that cell growth was greatly inhibited. The activities of the antioxidant enzymes including superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), glutathione peroxide (GSH-PX) and glutathione S-transferase (GST) increased with the exposure concentration and decreased with the prolongation of exposure time. Cellular ascorbic acid (AsA) and reduced glutathione (GSH) systems were also involved in resisting oxidative stress of EMA by altering the composition of AsA and GSH pools. EMA exposure increased the contents of AsA, GSH, dehydroascorbate (DAsA) and glutathione (GSSG). However, the regeneration rate of AsA/DAsA did not change obviously between treatments and the control, while that of GSH/GSSG decreased significantly under 14 mmol/L EMA exposure on the 3rd day. These results showed that EMA-induced oxidative damage might be responsible for EMA inhibition on P. tricornutum growth and cellular antioxidant enzymes and non-enzymatic antioxidants were improved to counteract the oxidative stress.     

Oxidative stress and locomotor behaviour response as biomarkers for assessing recovery status of mosquito fish, Gambusia affinis after lethal effect of an organophosphate pesticide, monocrotophos

Recovery study was performed at regular intervals to establish the time course of 50% and 100% recovery in neurotransmitter enzyme (acetylcholinesterase, AChE, EC 3.1.1.7) and locomotor behaviour response of mosquito fish, Gambusia affinis exposed to lethal concentration (20.49 mg L⁻¹) of an organophosphorous pesticide, monocrotophos (MCP) for 96 h. In vitro AChE activity studies indicated that MCP could cause 50% inhibition (I₅₀) at 10.2 × 10⁻⁵ M. A positive correlation was observed between brain AChE activity and swimming speed during the recovery study. Also, the recovery response of the antioxidant enzymes superoxide dismutase (SOD, EC 1.15.1.1), catalase (CAT, EC 1.11.1.6) and glutathione reductase (GR, EC 1.6.4.2) as well as lipid peroxidation (LPO) as biomarkers of oxidative stress were assessed in viscera of G. affinis. The results showed that the MCP besides its inhibitory effect on target enzyme AChE activity and induction in antioxidant enzyme activities as a characteristic of oxidative stress, which can be used as biomarkers in the pesticide contaminated aquatic streams.     

Raf-1 is dually down regulated by p,p′-DDE via reduced thyroid hormone and activated ERK

Raf-1 is the best characterized member of the mammalian raf family. The raf-1 kinase has many important physiological functions but its regulation is complex. 1,1-Dichloro-2,2 bis(p-chlorophenyl) ethylene (p,p′-DDE), a major and important metabolite of organochlorine pesticide DDT, is a widespread environmental pollutant. Previous studies have reported that p,p′-DDE influences the MAPK pathway, but little details are known regarding how the raf-1 activity is influenced and regulated by p,p′-DDE in those events. And here, we used 20 male rats that received different doses of p,p′-DDE (0, 20, 60, 100 mg/kg b.wt) every other day by intraperitoneal injection for 10 days. Results showed that the raf-1 mRNA and protein expressions showed significant down-regulation. The thyroxine (T4) level and the protein kinase C alpha (PKCα) mRNA expression declined, but the raf kinase inhibitory protein (RKIP) up regulated. In addition, the p,p′-DDE-induced oxidative stress resulted in declines of glutathione peroxidase (GSH-PX) and superoxide dismutase (SOD) activities. The elevations of ERK mRNA level and phosphorylated ERK protein expression were also observed. Taken together, these results suggest that the raf-1 is dually down regulated by p,p′-DDE via two pathways. One pathway is that the p,p′-DDE exposure elevates RKIP level by decreasing T4 and PKCα level, and the increased RKIP eventually down regulates the raf-1. The other is that the p,p′-DDE exposure activates the ERK by oxidative stress, and the activated ERK down regulates the raf-1 through the negative feedback phosphorylation.     

Amelioratory effect of vitamin E on organophosphorus insecticide diazinon-induced oxidative stress in mice liver

Considering that the involvement of reactive oxygen species (ROS) has been implicated in the toxicity of organophosphate insecticides (OPIs), the aim of this study was to investigate the ameliorative properties of vitamin E (vitE) against the subchronic effect of diazinon (DZN) on oxidative damage markers such as lipid peroxidation (LPO) and the antioxidant defense system (ADS) in the liver of male MFI albino mice. The groups were intraperitoneally (i.p) administered with either vehicle or vitE (100 mg/kg body weight) or ¼ LD₅₀ of DZN (16.25 mg/kg b.w.) or ½ LD₅₀ of DZN; 32.5 mg/kg b.w) or ¼ LD₅₀-DZN + vitE or ½ LD₅₀ + vitE every consecutive day for 14 days. Hepatic damage markers analysis revealed that alanine transferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) were significantly decreased in both DZN doses. Also, the significantly increased levels of biomarkers of oxidative stress as LPO and protein carbonyl (PC) and the decreased antioxidant defenses like reduced glutathione (GSH), and free radical scavenger enzymes viz., catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and glutathione reductase (GSH-Rx) were noted in DZN-treated groups as compared to control group. Distinctly lower levels of GSH and increased levels of LPO, along with alterations in endogenous antioxidant enzymes were evident in hepatic toxicity of DZN which is dose-dependent. Hepatic specific marker enzymes were restored to normalcy in mice supplemented with vitE following treatment with DZN which otherwise was decreased in the DZN-treated mice. The results show that co-treatment of vitE with DZN prevents or diminishes the oxidative stress of DZN-treated mice and may act as a putative protective agent against DZN-induced liver tissue injury.     

Differential morphological and physiological responses of two oilseed Brassica species to a new herbicide ZJ0273 used in rapeseed fields

Weeds are considered as a major threat to the production of oilseed Brassica crops. The use of herbicides that are safe for crops and effective in controlling weeds is crucial for the agronomists and farmers. Propyl 4-(2-(4,6-dimethoxypyrimidin-2-yloxy)benzylamino)benzoate (ZJ0273), a derivative of 2-pyrimidinyloxy-N-aryl benzoate, is a new herbicide used in the rapeseed field. To evaluate the tolerance of Brassica species against this new herbicide, two cultivars of rapeseed Brassica napus cv. ZS 758 and Brassica rapa cv. Xiaoyoucai were tested by a foliar spray of ZJ0273 at the rate of 100, 500 and 1000 mg/L and a currently used ALS (acetolactate synthase)-inhibiting herbicide bispyribac-sodium (BS) at the rate of 100 mg/L. The results showed that both the cultivars of Brassica were less affected by ZJ0273 as compared to BS. Increasing level of ZJ0273 herbicide from 100 to 1000 mg/L increased the stress for the plants of both the cultivars as indicated by enhanced accumulation of malondialdehyde content. The activities of ALS and antioxidant enzymes (superoxide dismutase and peroxidase), soluble protein and sugar contents, photosynthetic system (SPAD value, photosynthetic rate and chlorophyll fluorescence) as well as the agronomic characters also declined consistently with each successive increase in ZJ0273 concentration. In general, the plants treated with 100 mg/L ZJ0273 recovered from the herbicide stress after 28 days. B. napus showed more tolerance than B. rapa to the new herbicide. Nevertheless, BS application at 100 mg/L did not allow the plants of both the cultivars to recover from the herbicidal stress.     

Selenium and vitamin E, natural antioxidants, protect rat cerebral cortex against dimethoate-induced neurotoxicity

Pesticides have been used in agriculture to enhance food production by eradicating unwanted insects and controlling disease vectors, nevertheless occupational exposure to high levels of these compounds can lead to neurodegenerative disorders, characterized by serious oxidative and neurotoxic effects. However, there is a lack of consensus as to which determinations are best used to quantify future risks arising from xenobiotic exposure and natural antioxidant interventions. Our study aims to determine the potential ability of selenium and/or vitamin E, used as nutritional supplements, to alleviate oxidative stress in cerebral cortex tissue induced by dimethoate, an organophosphorus pesticide. Adult Wistar rats were exposed either to dimethoate (0.2 g/L of drinking water), dimethoate + selenium (0.5 mg/kg of diet), dimethoate + vitamin E (100 mg/kg of diet), or dimethoate + selenium + vitamin E, for 30 days. Exposure to dimethoate increased malondialdehyde levels, protein carbonyl groups and advanced oxidation protein products, while Na⁺K⁺-ATPase, acetylcholinesterase and butyrylcholinesterase activities decreased in the cerebral cortex. An increase in glutathione peroxidase, superoxide dismutase and catalase activities and a decrease in glutathione, non-protein thiols and vitamin C levels were observed. Administration of selenium and/or vitamin E through the diet in dimethoate treated rats ameliorated the biochemical parameters cited above. The histological findings confirmed the biochemical results. The model of this study that we employed characterized the relationships between dimethoate-induced neurotoxicity and its alleviation by natural antioxidants like selenium and vitamin E. These elements may be considered beneficial for the protection of cerebral cortex against injury induced by dimethoate.     

Behavioral, morphological deformities and biomarkers of oxidative damage as indicators of sublethal cypermethrin intoxication on the tadpoles of D. melanostictus (Schneider, 1799)

Concerns have been raised that the amphibian larval stages are particularly at risk and may be vulnerable to adverse effects of pesticides. The present study reports acute toxicity of cypermethrin at 24, 48, 72 and 96 h through static renewal bioassay test for Duttaphrynus melanostictus. The LC₅₀ values were 5.15, 4.55, 3.95, and 3.34 μg/L for 24, 48, 72, and 96 h respectively. At sublethal concentration (0.33 μg/L) behavioral, morphological and biochemical changes were studied. The behavioral and morphological anomalies observed in the present study are typical signs of cyano pyrethroid poisoning. Significant changes were observed in total, soluble, and structural proteins. The depletion of all the protein fractions observed in this investigation led to progressive protein oxidation and catabolism of proteins. Decreased protein level has resulted in a marked elevation of free amino acid levels at all time intervals. The induction of catalase, glutathione-S-transferase activities and elevation in the levels of hydrogen peroxide, reduced glutathione, and malondialdehyde eventually lead to oxidative damage of biomolecules, showing that the generation of reactive oxygen species and oxidative stress are involved in the toxicity induced by cypermethrin. Indicating increased susceptibility of tadpoles. Thus, an exposure to cypermethrin at sublethal concentration had catastrophic effect on tadpoles of D. melanostictus.     

Enhanced extracellular laccase activity as a part of the response system of white rot fungi: Trametes versicolor and Abortiporus biennis to paraquat-caused oxidative stress conditions

Effects of paraquat dichloride (PQ) on the laccase (LAC) activity and some biochemical parameters of Trametes versicolor and Abortiporus biennis strains belonging to white rot Basidiomycetes fungi were examined. PQ water solution was added to 10-day-old stationary cultures cultivated on a liquid medium. Having measured the activity of extracellular laccase during the first 120 h, we found that the addition of 25 μM paraquat to T. versicolor and 20 μM paraquat to A. biennis cultures significantly stimulated the LAC activity in comparison to the control value (without PQ). Native PAGE gel analysis demonstrated that no new isoforms of laccase appeared in the presence of PQ stress. The increase of LAC activity was connected with dry weight loss. Enhanced activity of extracellular superoxide dismutase was observed during the first 48 h after PQ application in both investigated strains. The PQ-treatment also caused an evident increase of catalase activity, formaldehyde level and depletion of glutathione in T. versicolor as well as in A. biennis mycelia.     

Effect of ginger supplementation on developmental toxicity induced by fenitrothion insecticide and/or lead in albino rats

Evaluation of the antioxidant and antiteratogenic role of ginger Zingiber officinale polyphenols against the toxicity induced by fenitrothion and/or lead in female albino rats were investigated. Adult virgin females were divided into 8 groups and were orally treated as follow: control (C), 1% w/w of ginger (G), 120 μg/animal lead as lead acetate (L), 10 mg/kg of fenitrothion (F), lead (120 μg/animal) fenitrothion (10 mg/kg) (LF), ginger (1%w/w) + fenitrothion (10 mg/kg) (GF), ginger (1%w/w) + lead (120 μg/animal) (GL), ginger (1%w/w) + lead (120 μg/animal) + fenitrothion (10 mg/kg) (GLF). Treatments were expanded for 28 days before pregnancy and during gestation period from zero to 6th day. Blood samples were taken at the day 20th of gestation and animals were sacrificed to investigate the effect of tested substances on dams and development of their fetuses. Inhibition in AchE in (F) and (LF) groups and elevation in plasma AchE in (L) groups were observed. Elevation in oxidative stress biomarker malondialdehyde (MDA) was recorded in all intoxicated groups concomitants with reduction in total reduced glutathione (GSH) and reduction in the activity of glutathione S-transferase (GST). Elevation in liver function biomarkers alanin amintransferase (ALT) and aspartate aminotransferase (AST) and reduction in plasma total protein and albumin were recorded in (F), (L) and (LF). Supplementation with ginger in diet attenuates the alteration in MDA, GSH, GST, ALT and AST, however, it failed to counteract the effect of F, L and LF on AchE, total protein and albumin. Significant alterations in maternal toxicity were recorded in (GF, GL, LF and GLF) compared with control group. Also, parameters of embryotoxicity and fetotoxicity indicated significant decrease in litter number that observed in F and L and the number of dead fetus/dam and litters number increased in L group. Supplementation with ginger decreased each of the number of died fetus, growth retardation and fetal length, while, it increased fetal weight. As regards to, teratological aspects, the percentage of skeletal malformations and visceral anomalies were observed in all feti obtained from treated groups with different percentages. Supplementation with ginger slightly attenuates the developmental toxicity of fenitrothion and/or lead.     

Activation of paraquat in the earthworm Allolobophora chlorotica is mediated by NAD(P)H-cytochrome c reductase activities

This study reports that earthworms, Allolobophora chlorotica, are capable of biotransforming paraquat, a toxic herbicide, resulting in the formation of reactive oxygen species (ROS). We found that in earthworms the reduction of paraquat is mediated by NADPH- and NADH-cytochrome c reductase activities. The formation of superoxide anion (O₂⁻) from the incubation of paraquat with the earthworm extracts was demonstrated by using both Cypridina luciferin analog (CLA) chemiluminescence and the SOD-inhibitable cytochrome c reduction reaction. In addition, in vivo exposure of earthworms to paraquat in solution (24 and 48 h) was performed to investigate whether or not the herbicide affects the levels of the NAD(P)H-cytochrome c reductase activities. Although in vitro NADPH-cytochrome c reductase reduces paraquat more easily than the NADH-dependent activity, after the in vivo exposure an increase of NADH-cytochrome c reductase activity(s) by 12% compared to control values was observed, whereas NADPH-cytochrome c reductase activity was not affected. Xanthine oxidase (XO) is an enzyme implicated in paraquat toxicity, however, no XO was detected in earthworm extracts nor hypoxanthine was a source of electrons for the herbicide reduction. For comparative reasons menadione, a redox cycling quinone, was also incubated with the earthworm extracts. It was found that the incubation of menadione with earthworm extracts formed about two times more (O₂⁻) than with paraquat. It is concluded that the exposure of paraquat to earthworms could elicit radical formation and consequently toxic effects via oxidative stress-mediated mechanisms. The reduction of paraquat by the reductases leads to the formation of paraquat radical, which reacts with molecular oxygen, accounting for the formation of superoxide anion. Further studies are required to conclude that the observed increase of NADH-cytochrome c reductase activity(s) should be used as a biomarker for paraquat exposure in earthworms.     

Effects of N-acetylcysteine on oxidative responses in the liver of fenthion exposed Cyprinus carpio

The aim of this study was to evaluate the effects of different N-acetylcysteine doses on the tolerance to fenthion-induced oxidative stress, alterations in glutathione metabolism and cholinesterase specific activities in the liver by using freshwater fish Cyprinus carpio (Cyprinidae) as a model organism. An acute toxicity study was carried out to determine 96-h median lethal concentration of fenthion for this species (2.16 mg/L) and 80% of this concentration was applied in toxicity studies. Four groups, each containing eight fish were constituted as follows: Control group, fenthion treated group, 0.5 or 400 mg/kg NAC-injected + fenthion-treated groups. Biochemical analyses were carried out spectrophotometrically. Fenthion treatment significantly decreased total glutathione and glutathione levels, glutathione/glutathione disulfide ratio together with glutathione reductase and γ-glutamylcysteine synthetase specific enzyme activities. The higher dose of N-acetylcysteine increased the toxic effects of fenthion and γ-glutamyl transpeptidase specific activity while decreasing glutathione S-transferase specific activity. However, injection of the lower dose provided a limited protection against fenthion toxicity. In all exposure groups, lipid peroxidation increased and total protein levels decreased, while protein depletion was prevented by low dose of N-acetylcysteine application. Acetylcholinesterase and butyrylcholinesterase activities were at similar levels in the liver of C. carpio. A dose-dependent inhibition was observed in butyrylcholinesterase activity by N-acetylcysteine application. The results showed that fenthion had a significant oxidative stress inducing potential through the reduction of glutathione redox capacity. The critical point for overcoming oxidative stress by N-acetylcysteine in fenthion toxicity was the selection of the dose; N-acetylcysteine exerted its toxic effects by means of oxidative stress in fish liver at the higher dose.     

Antioxidant role of propolis extract against oxidative damage of testicular tissue induced by insecticide chlorpyrifos in rats

Pesticides induce oxidative stress leading to generate free radicals and alternate the antioxidant or oxygen free radical scavenging enzyme system. This study was conducted to investigate the oral toxicity of chlorpyrifos toward male rat and the oxidative stress of the sub-lethal dose (9 mg/kg; 1/25 LD₅₀) on the lipid peroxidation level (LPO), reduced glutathione content (GSH) and antioxidant enzymes; catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione-S-transferase (GST) activities of testicular tissue. Also, the protective effects of propolis extract (50 mg/kg b.w.) alone or in combination with chlorpyrifos were investigated. The oral administration of chlorpyrifos significantly caused elevation in LPO level by 1.79-fold as compared to control. The activities of antioxidant enzymes including CAT, SOD, GPx and GST were decreased significantly (23.66%, 27.75%, 29.13% and 11.52%) as well as the level of GSH decreased by 21.97% in testicular tissue as compared to control animals. Co-administration of propolis extract with chlorpyrifos or alone in male rats decreased LPO level, normalized CAT, SOD GPx and GST activities, while GSH content was increased in testicular tissue. We conclude that propolis extract significantly reduces chlorpyrifos-induced oxidative stress in rat testis and the protective effect of the pre-treatment with propolis extract as attenuating agent could be due to its antioxidant properties.     

Protective effects of Nigella sativa oil on propoxur-induced toxicity and oxidative stress in rat brain regions

Propoxur (PPr) is a widely used broad spectrum carbamate insecticide mainly used to control household pests. Because of the widespread use of pesticides for domestic and industrial applications, evaluation of their neurotoxic effects is of major concern to public health. The aim of the present study was to evaluate the possible protective effects of Nigella sativa oil (NSO), an antioxidant agent, against PPr-induced toxicity and oxidative stress in different brain regions of rats including cerebellum, cortex and hippocampus. In the present study, 32 male Sprague-Dawley rats were used and divided into four equal groups. Group 1 was allocated as the control group. Groups 2-4 were orally administered 1 ml/kg/bw/day NSO, 8.51 mg/kg/bw/day PPr or NSO plus PPr, respectively, for 30 days. Lipid peroxidation (LPO), protein carbonyl content (PCC) and acetylcholine esterase activity (AChE) were determined. Enzymatic antioxidant activities [superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione-S-transferase (GST)] and non-enzymatic antioxidants [reduced glutathione (GSH)] were determined. PPr treatment significantly increased the levels of LPO, PCC and oxidized glutathione (GSSG) in brain regions. On the contrary, levels of GSH and the activities of SOD, CAT, GSH-Px, GST and AChE were significantly decreased. NSO treatment to PPr intoxicated rats restored such biochemical parameters to within control levels except GST activity, emphasizing its antioxidant role. We conclude that NSO significantly reduces PPr-induced toxicity and oxidative stress in rat brain regions via a free radicals scavenging mechanism.     

Coexpression with Auxiliary β Subunits Modulates the Action of Tefluthrin on Rat Na(v)1.6 and Na(v)1.3 Sodium Channels

The erythrocyte, due to its role as O₂ and CO₂ transporter, is under the constant exposure to reactive oxygen species and oxidative stress. The objective of this study was to investigate the ability of 2,4-D to induce oxidative stress in blood of male wistar rats. Rats were randomly divided into four groups: a control group and three treated groups receiving by gavage 15, 75 and 150 mg, respectively, of 2,4-D/kg/BW/day for 28 days. Results showed that 2,4-D caused significant negative changes in the investigated biochemical parameters. In fact, 2,4-D exposition strongly increases LDH, by contrast, there is a statistically significant decrease in Hgb levels. The malondialdehyde level was significantly increased in 2,4-D treated groups. Fatty acid composition of the erythrocytes was also significantly changed with 2,4-D exposure, in favor of the peroxidation of polyunsaturated fatty acids. Furthermore, antioxidant enzyme (SOD, CAT, GPx, and GR) activities in erythrocytes were significantly decreased. Thus, our results indicated the potential effects of 2,4-D to cause oxidative stress in rat erythrocytes. Therefore, at higher doses, 2,4-D may play an important role in the development of vascular disease via lipid peroxidation and oxidative stress.     

Avermectin exposure induces apoptosis in King pigeon brain neurons

The effect of avermectin was studied on King pigeon brain nerve cells by cytotoxicity [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide, MTT] and apoptosis [acridine orange/ethidium bromide (AO/EB) assay, transmission electron microscope (TEM) evaluation, measurement of mitochondrial membrane potential (Δψm), phosphatidylserine (PS) exposure, caspases activities, DNA fragmentation, reactive oxygen species (ROS) and caspase-3 mRNA expression] within the 2.5–10 μg L⁻¹ concentration-range. The results revealed that within the concentrations of 2.5–10 μg L⁻¹, avermectin showed obvious cytotoxicity and induced apoptosis in a dose-dependent manner to neurons of King pigeon in vitro. Cell viability were 99.93 ± 8.52%, 82.02 ± 4.99% and 78.23 ± 5.67% after 24 h of treatment with avermectin at the concentrations of 0, 2.5 and 5 μg L⁻¹, which decreased to 56.36 ± 2.17% of 10 μg L⁻¹. Treated cells showed typical apoptosis morphological changes including cytoplasmic vacuolation, chromatin condensation, unclear nuclear membrane and decreased/swollen mitochondria. Typical biochemical hallmarks of apoptosis including Δψm loss, PS exposure, activations of caspase-3, caspase-8 and caspase-9, DNA fragmentation were observed too. Moreover, the levels of ROS in the avermectin treatment groups increased significantly compared to control group. Furthermore, the caspase-3 mRNA levels increased significantly following AVM treatment. In conclusion, our experimental results show that avermectin has cytotoxicity to brain neurons of King pigeon in vitro and the mechanism of neurotoxicity induced by avermectin is closely related to apoptosis.