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1.
Pesticides may induce oxidative stress leading to generate free radicals and alternate antioxidant or oxygen free radical scavenging enzyme system. This study was conducted to investigate the acute toxicity of chlorpyrifos toward male mice and the oxidative stress of the sub-lethal dose (1/10 LD50) on the lipid peroxidation level (LPO), reduced glutathione content (GSH) and antioxidant enzymes; catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), glucose-6-phosphate dehydrogenase (G6PD), and glutathione-S-transferase (GST) activities. Also, the protective effects of vitamin C (200 mg/kg body weight, bw) 30 min before or after administration of chlorpyrifos were investigated. The results demonstrated that the LD50 value of chlorpyrifos was 134.95 mg/kg bw. The oral administration of 13.495 mg/kg chlorpyrifos significantly caused elevation in LPO level and the activities of antioxidant enzymes including CAT, SOD and GST. However, GPx activity remained unchanged, while the level of GSH and G6PD activity were decreased. Vitamin C treatment to chlorpyrifos intoxicated mice decreased LPO level and GST activity, normalized CAT, SOD and G6PD activities, while GSH content was increased. We conclude that vitamin C significantly reduces chlorpyrifos-induced oxidative stress in mice liver and the protective effect of the pre-treatment with vitamin C is better than the post-treatment.  相似文献   

2.
This study was undertaken to evaluate the antioxidant effect of vitamins C and E against oxidative stress, apoptosis and histological changes of kidney and retina in CPF-treated rats. Forty male Sprague-Dawley rats were divided into four groups including the control group, the group treated orally with a single dose of CPF (63 mg/kg b.w.), the group injected intramuscularly (i.m.) with vitamin C (250 mg/kg b.w.), and intraperitonealy (i.p.) with vitamin E (150 mg/kg b.w.) daily for 7 days and the group treated with CPF (single dose) and injected with vitamins (for 7 days). The results showed that CPF induced apoptosis and severe oxidative stress as indicated by the significant increase in MDA and sFasL concentration and the significant decrease in GSH concentration in serum. Co-administration of vitamins C and E ameliorate these toxic effects and improved the histological pictures of kidneys and retinas. It could be concluded that combined administration of vitamins C and E is useful in the routine therapy for the protection against tissue damage induced by CPF.  相似文献   

3.
The purpose of this study, carried out on male Wistar rats, was to evaluate the beneficial effects of garlic (Allium sativum) extract injections upon lindane-induced damages in testes, brain and thyroid function. Under our experimental conditions, lindane poisoning (in drinking water for 30 days, supplying about 50 mg/kg body weight per day) resulted in a decreased weight of testes, epididymides, prostate gland and seminal vesicles (−52%, −42%, −50% and −5%, respectively), a decrease of spermatozoa count and motility (−56%, −37%, respectively), an increased level of free thyroxin (+84%) and decreased levels of TSH and FSH in serum (−74%, −77%, respectively). In addition, lindane treatment triggered an oxidative stress in testes and brain as revealed by an increased level of lipids peroxidation (TBARS) (+96%,+92%), an increase of superoxide-dismutase activity in testes (+69%) and a decrease of glutathione-peroxidase and catalase activities in testes and brain (−52%, −34% and −49%, −45%, respectively). These lindane-induced changes were almost reversed to normal in animals injected with a garlic extract (an amount corresponding to 300 mg fresh garlic/kg/day), what confirms a beneficial effect of this vegetal source of anti-oxidants.  相似文献   

4.
This study examined the effects of chlorpyrifos in the rat erythrocyte antioxidant system and evaluated the ameliorating effects of catechin and quercetin on the oxidative damage induced by chlorpyrifos. Sexually mature male Wistar rats were given chlorpyrifos (5.4 mg/kg, 1/25 of the oral LD50), catechin (20 mg/kg), quercetin (20 mg/kg), catechin plus chlorpyrifos, and quercetin plus chlorpyrifos daily via gavage for four weeks. No statistical differences were found in the catechin-only and quercetin-only groups compared with the control group. By the end of the fourth week, chlorpyrifos alone increased the levels of malondialdehyde (MDA) and decreased superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities compared with the control group in rat erythrocytes. In the catechin-plus-chlorpyrifos and quercetin-plus-chlorpyrifos groups, there were statistically significantly decreased MDA levels and increased SOD, CAT, and GPx activities compared with the chlorpyrifos-only group. Thus, it appears that catechin and quercetin ameliorate chlorpyrifos-induced oxidative stress in rat erythrocytes in vivo.  相似文献   

5.
Organophosphorus insecticides (OPIs) may induce oxidative stress leading to generation of free radicals and alteration in antioxidant system of animals. Many studies reported that enzymatic and non-enzymatic antioxidant may play protective role against OPIs induced toxicity in human and rats. The aim of present study was to investigate the possible protective role of vitamin E on ethion-induced hepatotoxicity in rats using qualitative, quantitative and biochemical approaches. Adult male albino rats of Wistar strain were randomly divided into four groups; each group consists of six animals. Animals were treated for a period of 28 days. Group I (control group received corn oil); Group II [ethion treated (2.7 mg/kg bw/day)]; Group III (vitamin E treated (50 mg/kg of bw/day)]; Group IV (ethion + vitamin E treated). Animals were sacrificed after 7, 14, 21 and 28 days by decapitation and liver tissue was used for the measurement of proteins, lipid peroxidation (LPO), reduced glutathione (GSH) content and activities of antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) glutathione reductase (GR) and glutathione-S-transferase (GST). Erythrocytes were analyzed for acetyl cholinesterase activity. The result of this study shows that in vivo administration of ethion caused a significant induction of oxidative damage in liver tissue as evidenced by increased level of LPO and decreased GSH content. Ethion toxicity also led to a significant increase in the activities of SOD, CAT, GPx and GST in liver tissue. In addition, decrease in GR activity was observed in ethion administered rats compared to control. Histopathological findings revealed that exposure to ethion caused damage in liver tissue. However, simultaneous supplementation with vitamin E restored these parameters partially. In conclusion, the results of the current study revealed that ethion-induced toxicity caused lipid peroxidation, alterations in the antioxidant enzymes and histopathological changes in liver. Supplementation of vitamin E exhibited protective effect by inhibiting ethion-induced toxicity in liver and erythrocytes.  相似文献   

6.
The aim of this study was to investigate effects of an organophosphate insecticide, diazinon (DI), on pancreas, and possible ameliorating role of vitamins E and C. We examined both in vivo and in vitro effects of DI on serum activities of alkaline phosphatase (ALP), γ-glutamyltransferase (GGT), amylase, and lipase enzymes. We also evaluated possible ameliorating effects of vitamins E and C combination against DI toxicity and blood levels of thiobarbituric acid reactive substances (TBARS) only in vivo. In vivo experimental groups were: control group, DI-treated group, and DI + vitamins E plus C-treated group. In vitro study groups were: control group and DI-treated group. The biochemical analyses were determined in in vitro experiments at both hour 0 and 24 while in in vivo experiments were determined only at hour 24. Lipase activity and TBARS level were found increased by DI in in vivo experiments while lipase activity was found decreased in in vitro experiments. Amylase and ALP activities were found decreased by DI in both in vivo and in vitro experiments. Also, the combination of vitamins E and C was found to partially improve these disorders. These results suggest that DI treatment causes pancreas damage via increasing oxidative stress in rats, and a combination vitamins E and C can reduce this lipoperoxidative effect.  相似文献   

7.
Organophosphate (OP) pesticides are among the most widely used synthetic chemicals for controlling a wide variety of pests. Chlorpyrifos (o,o′-diethyl-o-3,5,6-trichloro-2-pyridyl phosphorothionate, CPF) is among the leading OP pesticides used extensively throughout the world including India while methyl parathion (o,o-di methyl-o-p-nitrophenyl phosphorothioate, MPT) another OP compound, widely used as insecticide and acaricide to control many biting or sucking pests of agricultural crops. Present study was carried out to compare the chronic toxicity of CPF and MPT, their potential to generate oxidative stress and ameliorating effects of antioxidant vitamins in brain of rats. Results of the present study clearly demonstrated that the oral exposure of CPF or MPT, generated oxidative stress in different parts of rat brain consequently accumulating malondialdehyde (MDA) and 4-hydroxynonanal (4HNE), the two major end products of lipid peroxidation, in all the three brain regions i.e. fore-, mid- and hind-brain. The levels of hydrogen peroxide (H2O2) were also increased in all the three brain regions when compared with control. CPF and MPT exposure caused decrease in the levels of reduced glutathione (GSH) and increase in the levels of oxidized glutathione (GSSG) in all the three brain regions. The increase in the levels of MDA, 4HNE, H2O2 and GSSG was less pronounced when CPF or MPT was given to the rats fed with a mixture of vitamin A, E and C. The present findings clearly show that oral intake of a mixture of vitamin A, E and C protects the rats from MPT or CPF induced oxidative stress and suggest that this treatment alleviates the toxicity of these pesticides to a greater extent.  相似文献   

8.
9.
The effects of organophosphate insecticide methidathion (MD) on kidney tissue and the ameliorating effects of a combination of vitamins E and C against subchronic MD toxicity were evaluated in rats. Experimental groups were: control group (group I), 5 mg/kg body weight MD-treated group (group II), and 5 mg/kg body weight MD plus vitamin E plus vitamin C treated group (group III). The groups II and III were treated orally with MD on five days a week for four weeks. Vitamins E and C were injected at doses of 50 mg/kg body weight, i.m. and 20 mg/kg body weight, i.p., respectively, 30 min after the treatment of MD in the group III. Rats were anaesthesized and venous blood samples were collected by direct right ventricle heart puncture, in addition, the right kidney was removed for histopathological examinations and malondialdehyde (MDA) analyses after four weeks. The serum activity of cholinesterase (ChE) and the kidney level of malondialdehyde, and kidney histopathology were studied in rats. MD caused decreased ChE activity (group I: 2114 ± 63 U/L, group II: 1455 ± 100 U/L) and increased MDA level (group I: 147 ± 20.2 nmol/mg protein, group II: 236 ± 25.6 nmol/mg protein), and kidney damage in rats. Furthermore, a combination of vitamins E and C restored partially (ChE activity: 1670 ± 111 U/L, MDA level: 159 19.4 nmol/mg protein) this changes in MD-treated rats.  相似文献   

10.
A hundred and sixty female white mice, each weighing 35-40 g, were used in this study. The animals were assigned into eight groups as one control group and 7 experimental groups. Groups 2, 3 and 4 were administered N-acetylcysteine (NAC), proanthocyanidin and vitamin E alone, at doses of 100 mg/kg/body weight/day by intra-peritoneal, oral route and, intramuscular, respectively. Group 5 was administered a single dose of cyfluthrin (100 mg g/kg/body weight ∼1/3LD50) by oral, whereas Groups 6, 7 and 8 were given cyfluthrin+NAC, cyfluthrin+proanthocyanidin and cyfluthrin+vitamin E, at the same dose, respectively. The administration of the drugs was initiated following the administration of cyfluthrin, and continued until the end of the seventh day of the study. Blood samples were collected from each group, 24 h, and 3, 7 and 9 days after the administration of cyfluthrin for the assessment of blood malondialdehyde (MDA) levels and superoxide dismutase (SOD) and catalase (CAT) activities. According to the data obtained, compared to the control group, increase in the plasma MDA level of the group administered cyfluthrin alone, and decrease in erythrocyte SOD activities in some periods and CAT activities in all periods were determined. On the other hand, especially, MDA levels and CAT activities were observed to move closer to values of the control group, in the groups that were administered NAC, proanthocyanidin and vitamin E in addition to cyfluthrin. In other words, in most periods, decrease in plasma MDA levels, and increase in erythrocyte CAT and SOD activities were observed in comparison to the group administered cyfluthrin alone. Statistical analyses demonstrated significant differences to exist between the groups on the third, seventh and ninth days with respect to plasma MDA levels, and the third and ninth days with respect to erythrocyte SOD and CAT activities (P < 0.05). However no significant difference was demonstrated in any of the periods in the groups that were administered NAC, proanthocyanidin and vitamin E alone in comparison to the control group (P > 0.05). In view of the parameters examined, animals were concluded to be affected by cyfluthrin and the administration of the three compounds at the indicated doses and for the indicated periods were considered to alleviate the adverse effects of cyfluthrin partly throughout the study period.  相似文献   

11.
Methyl parathion is an organophosphate insecticide that has been used in agriculture and domestic for several years. Vitamin C (200 mg/kg bw per day) + vitamin E (200 mg/kg bw per day), methyl parathion (0.28 mg/kg bw per day) and vitamin C (200 mg/kg bw per day) + vitamin E (200 mg/kg bw per day) + methyl parathion (0.28 mg/kg bw per day) combination were given to rats orally via gavage for 7 weeks. Body and kidney weights, malondialdehyde (MDA) levels and histopathological changes were investigated at the end of 4th and 7th weeks comparatively with control group. When methyl parathion-treated group and vitamins C and E + methyl parathion-treated group were compared to control group body and kidney weights decreased significantly at the end of 4th and 7th weeks. MDA levels increased in kidney tissues of the methyl parathion- and vitamins C and E + methyl parathion-treated groups compared to control group. MDA levels decreased significantly in vitamins C and E + methyl parathion treated group compared with methyl parathion treated group at the end of 4th and 7th weeks. In our light microscopic investigations, after 4 weeks of methyl parathion exposure, glomerular atrophy and vascular dilatation, and after 7 weeks, necrosis and edema were observed in the kidney tissues. After 4 weeks of vitamins C and E + methyl parathion exposure, mononuclear cell infiltrations, and after 7 weeks, calcification were detected in the kidney tissues.  相似文献   

12.
13.
Methyl parathion is an organophosphate insecticide that has been used in agriculture and domestic for several years. Vitamin C (200 mg/kg bw per day) + vitamin E (200 mg/kg bw per day), methyl parathion (0.28 mg/kg bw per day) and vitamin C (200 mg/kg bw per day) + vitamin E (200 mg/kg bw per day) + methyl parathion (0.28 mg/kg bw per day) combination were given to rats orally via gavage for 7 weeks. Body and testis weights, sperm counts, sperm motility, sperm morphology and histopathological changes in the testes were investigated at the end of 24 h, 4th and 7th weeks comparatively with control group. No pathological changes were observed in all parameters at the end of 24 h. When methyl parathion-treated group and vitamins C and E + methyl parathion-treated group were compared to control group, body and testis weights decreased significantly at the end of 4th and 7th weeks. It was observed that, at the end of 4th and 7th weeks there was a statistically significant decrease in sperm counts and sperm motility, increase in abnormal sperm morphology when methyl parathion- and vitamins C and E + methyl parathion-treated group were compared to control group. While sperm counts increased at the end of 4th and 7th weeks, sperm motility increased at the end of 7th week when vitamins C and E + methyl parathion-treated group compared with methyl parathion-treated group, no changes were observed in abnormal sperm morphology at the end of 4th and 7th weeks. In our light microscopic investigations, after 4 and 7 weeks of methyl parathion exposure, necrosis and edema were observed in the seminiferous tubules and interstitial tissues. After 4 and 7 weeks of vitamins C and E + methyl parathion exposure, degenerative changes were detected in the seminiferous tubules while no pathological findings were observed in the interstitial tissues. According to the present study, we conclude that vitamins C and E reduces methyl parathion testicular toxicity, but it does not protect completely.  相似文献   

14.
Recent several studies have reported that oxidative stress could be an important component of the mechanism of cardiotoxicity due to organophosphate-induced toxicity. The aim of this study is to evaluate the oxidative and antioxidative parameters in cardiac toxicity of organophosphate poisoning, and determine the effects of atropine and pralidoxime on this parameters. The experimental groups were randomly divided into five groups as control (corn oil), dichlorvos (30 mg/kg), atropine (10 mg/kg), pralidoxime (40 mg/kg), and atropine (10 mg/kg) + pralidoxime (40 mg/kg) groups. Serum cholinesterase levels were suppressed with dichlorvos, and these reductions were inhibited with atropine and/or pralidoxime pretreatment. Serum, but not cardiac, total free sulfhydryl groups and paraoxonase activities were significantly increased in the pralidoxime group when compared to the control group. Serum arylesterase activities were elevated in the dichlorvos, atropine, pralidoxime, and atropine + pralidoxime groups when compared to the control group (P < 0.05). Total oxidant status, oxidative stress index, malondialdehyde and catalase activities in serum and cardiac tissues were not markedly different between the groups. No significant changes were also observed with cardiac myeloperoxidase and serum ceruloplasmin activities. In conclusion, these results showed that acute dichlorvos administration did not cause marked cardiac damage, and oxidative stress probably does not play a major role in dichlorvos-induced poisoning. On the other hand, especially pralidoxime treatment markedly increased the serum total free sulfhydryl groups, paraoxonase and arylesterase activities. However, the underlying mechanisms for these changes are not exactly known.  相似文献   

15.
Deltamethrin and thiachloprid are an α-cyano class pyrethroid and neonicotinoid insecticide, respectively. Recently, a pesticide combining deltamethrin and thiacloprid has also been released. In the present study, the acute and subacute toxic effects of deltamethrin, thiachlopride, and a combination of these insecticides, on the lymphoid organs (spleen, thymus and bone marrow), polymorphonuclear leukocytes (PMNs) and plasma of rats, were determined to better understand mammalian antioxidant-oxidant and inflammatory system responses. For this purpose, rats were treated orally with different doses of thiacloprid (single acute dose of 112.5 mg/kg); subacute dose of 22.5 mg/kg/day for 30 days; deltamethrin (single acute dose of 15 mg/kg); subacute dose (3 mg/kg/day for 30 days), or a combination of these pesticides. Results were compared with those from a comparable dosing regimen with the known immunosuppressive drug cyclophosphamide. Pesticide treatments caused significant changes in the levels of liver and kidney injury markers. Antioxidant enzyme (catalase and glutathione peroxidase), glutathione and plasma antioxidant levels decreased but lipid peroxidation increased in all lymphoid organs and the plasma. Glutathione-S-transferase and especially DT-diaphorase activity, decreased after thiacloprid treatment. Myeloperoxidase activity, carbonyl content, lipid peroxidation and total nitrite levels increased in PMNs and plasma. When evaluated as a whole, the oxidative and inflammatory stresses seen in the pesticide combination groups were not much more pronounced than in the groups treated with a single pesticide. In terms of the evaluated biochemical parameters, the pesticides showed similar effects to cyclophosphamide.  相似文献   

16.
The protective effects of zinc on liver and kidney injury induced by chlorpyrifos (CPF) were investigated in rats. Male and female rats were orally administered CPF at a dose of 6.75 mg kg−1 body weight for 28 consecutive days. An additional CPF group received zinc (227 mg l−1) in drinking water throughout the experimental duration. Two groups more served as controls. Administration of CPF resulted in a significant increase in serum lipid peroxidation (LPO) level, while induced significant decreases in the activities of plasma superoxide dismutase (SOD), glutathione-S-transferase (GST) and serum acetylcholinesterase (AChE) either in male or female rats. Similarly, a significant increase in the levels of various serum marker enzymes [e.g. aminotransferases (AST and ALT), lactate dehydrogenase (LDH) and gamma glutamyl transferase (GGT)] and increase the level of total protein, uric acid and creatinine. In contrast, co-administration of zinc to CPF-treated animals restored most of these biochemical parameters to within normal levels. In case of AChE, supplementation of zinc showed little alteration in the activity of this enzyme especially in male rats treated with CPF. CPF caused histopathological change in liver and kidneys of male and female rats. However, zinc administration to CPF-treated animals resulted in overall improvement in liver and kidneys damage, emphasizing its antioxidant role. In light of the available data, it can deduce that CPF-induced lipid peroxidation, oxidative stress, liver and kidneys damage in male and female rats, and conjunction supplementation of zinc has resulted in pronounced ameliorating effect.  相似文献   

17.
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.  相似文献   

18.
The present study was carried out to investigate the sub-lethal toxicity of technical grade deltamethrin (a synthetic pyrethroid) of concentration 1.61 μg/L (1/3rd of 96 h LC50) on hematological and biochemical parameters of catla (Catla catla) fingerlings and its amelioration through dietary vitamin C. The deltamethrin exposed fishes were fed with different levels of supplemented vitamin C such as 50, 250, 500 and 1000 mg/kg diet to see its ameliorating effect by assaying hematological parameters viz. total erythrocyte count (TEC), total leukocyte count (TLC), hemoglobin content (Hb), total serum protein, albumin, globulin, albumin–globulin ratio and biochemical parameters such as lactate dehydrogenase (LDH), acetylcholine esterase (AChE), alanine amino transferase (ALT), aspartate amino transferase (AST), total adenosine triphosphatase (ATPase), magnesium adenosine triphosphatase (Mg2+-ATPase) and sodium potassium adenosine triphosphatase (Na+, K+-ATPase) activities. The finding of this study showed that deltamethrin had negative effect on the hematological and biochemical parameters of Catla catla. The experimental group, which was exposed to deltamethrin and fed with normal diet showed significantly lower values (P ? 0.05) of all parameters studied except ALT activity. This might be due to possible disruption of hematopoiesis and proteosynthesis. However, the fish fed with varied concentration of vitamin C in diets neutralized the toxic effect of deltamethrin, as evidenced by significantly lowered hematological and biochemical response. Vitamin C @ 1000 mg/kg diet was the most effective in amelioration of harmful effect of deltamethrin on hematological and biochemical parameters of catla fingerlings. The result suggests that vitamin C can be effectively used to neutralize the toxic effect of deltamethrin on catla.  相似文献   

19.
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.  相似文献   

20.
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.  相似文献   

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