2,3,7,8-Tetrachlorodibenzo-p-dioxin-induced impairment of glucose-stimulated insulin secretion in isolated rat pancreatic islets

We have explored the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) administration on the secretory function of isolated rat pancreatic islets. Twenty-four hours after TCDD administration (1 microg/kg b.w., i.p.), rats showed no significant differences in plasma glucose, insulin, triglycerides and leptin levels whereas plasma-free fatty acids were significantly increased with respect to untreated controls. In isolated islets, DNA and protein content were unchanged, whereas insulin content was significantly decreased in TCDD-treated rats. Incubation with different concentrations of glucose demonstrated a significant impairment of glucose-stimulated insulin secretion in islets isolated from TCDD-treated rats, whereas insulin release was better preserved upon alpha-ketoisocaproate stimulation. A significant reduction of [3H]-2-deoxy-glucose uptake was observed in pancreatic tissue of TCDD-treated rats, whereas no significant reduction in GLUT-2 protein levels was detectable by immunoblotting in islets from TCDD-treated rats. We concluded that low-dose TCDD could rapidly induce significant alterations of the pancreatic endocrine function in the rat.     

2,3,7,8-Tetrachlorodibenzo-p-dioxin-induced porphyria in genetically inbred mice: partial antagonism and mechanistic studies

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) (233 nmol/kg) causes a significant increase of hepatic uroporphyrin, heptacarboxyporphyrin, and total porphyrins in female C57BL/6 mice, ovariectomized C57BL/6 mice, male C57BL/10 mice, and male C57BL/6 mice 3 weeks after treatment. In contrast, 6-methyl-1,3,8-trichlorodibenzofuran (MCDF) was inactive at a dose of 750 mumol/kg. Cotreatment of the mice with TCDD (233 mol/kg) plus MCDF (750 mumol/kg) resulted in partial antagonism of TCDD-induced hepatic porphyrin accumulation only in the female mice. Parallel studies in female C57BL/6 mice showed that the TCDD-induced porphyria was accompanied by the induction of hepatic microsomal aryl hydrocarbon hydroxylase (AHH) and ethoxyresorufin O-deethylase (EROD) activities and the depression of uroporphyrinogen decarboxylase (UROD). MCDF (750 mumol/kg) did not significantly affect these enzymes. In the cotreatment studies (MCDF plus TCDD), MCDF partially antagonized TCDD-induced hepatic porphyrin accumulation but did not affect the levels of hepatic AHH, EROD, or UROD. These results indicate that other factors, in addition to the induction of cytochrome P450-dependent monooxygenases and depressed UROD activity, are important in TCDD-induced porphyria in C57BL/6 female mice.     

Effect of chitosan oligosaccharide on 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced oxidative stress in mice

The abilities of two types of chitosan oligosaccharides, chitosan oligosaccharide I (1-kDa相似文献   

Acute stressor-selective effects on homocysteine metabolism and oxidative stress parameters in female rats

Homocysteine levels are affected by diet factors such as vitamin deficiencies, non-diet factors such as genetic disorders, and stress exposure. Hyperhomocysteinemia has been implicated in several disorders, including cardiovascular disease, depression, schizophrenia, Alzheimer's and Parkinson's disease. Since sex differences play a role both in stress responses and in susceptibility to various diseases, the objective of this study was to evaluate possible alterations in homocysteine metabolism including cysteine, folate, and vitamin B(6), and oxidative stress markers in female rats exposed to different types of acute stress. Female rats were randomly distributed into eight groups according to stress manipulation (restraint, swimming, cold and control) and estrous cycle (diestrus and estrus). In general no significant differences were seen between rats in estrus and diestrus. Restraint stress was the only type of stress that altered homocysteine concentrations (+33% relative to controls). An increase in levels of thiobarbituric acid reactive substances (TBARS) and a decrease in total glutathione (GSHt) concentration were also observed in animals subjected to restraint and swimming stress, suggesting the possibility of oxidative damage. Thus, both the homocysteine results and the oxidative stress data indicated that restraint stress was the most powerful stress manipulation in female rats, as previously observed in male rats. These findings indicate that hormonal and gonadal differences do not interfere with stress responses related to homocysteine metabolism and suggest that putative gender-related differences in homocysteine responses are probably not involved in the differential prevalence of some diseases in human males and females.     

2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD) induces oxidative stress in the epididymis and epididymal sperm of adult rats

2,3,7,8-Tetrachlorodibenzo- p-dioxin (TCDD) is one of the most potent environmental contaminants, which has been shown to induce oxidative stress in testis and epididymal sperm of rats. However, the nature and mechanism of action of TCDD on the epididymis is not clear. The aim of the present study was to investigate whether induction of oxidative stress in epididymal sperm was direct effect of TCDD on epididymis. In the present studies, TCDD (0.1, 1.0 and 10 micro g/kg body weight per day) was administered orally to rats for 4 days. Twenty-four hours after the last treatment the animals were killed using anesthetic ether. Both epididymides were dissected out and epididymal sperm were collected by cutting the epididymides into small pieces in Ham's F-12 medium at 35 degrees C. The epididymal sperm and caput, corpus and cauda epididymides were homogenized and used for biochemical studies. Epididymal sperm counts did not decrease in the rats treated with TCDD. Administration of TCDD increased the production of reactive oxygen species such as hydrogen peroxide while the activities of antioxidant enzymes superoxide dismutase, catalase, glutathione reductase and glutathione peroxidase were found to be decreased in the epididymal sperm as well as in cauda epididymides. Lipid peroxidation also increased in the epididymal sperm and in the various regions of the epididymides after exposure to TCDD. The results indicated that TCDD induces oxidative stress in the epididymis and epididymal sperm by decreasing the antioxidant enzymes through induction of reactive oxygen species. Thus, the adverse effects of TCDD on the epididymal sperm were due to direct effect of TCDD on epididymis.     

Induction of oxidative stress in rat epididymal sperm after exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin

The ability of 2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD) to induce oxidative stress in various tissues of animals has been reported. The nature and mechanism of action of TCDD on the antioxidant system of sperm has not been studied. In the present study we have sought to investigate whether TCDD induces oxidative stress in the epididymal sperm of rats. Subchronic doses of TCDD (1, 10, and 100 ng/kg body weight per day) were administered orally to male Wistar strain rats for 45 days. After 24 h of the last treatment the rats were killed using diethyl ether. The epididymides were removed and cleared from the adhering tissues. Epididymal sperm were collected by cutting the epididymides into small pieces in Ham's F12 medium, and counted using a hemocytometer. The epididymal sperm counts in the TCDD-treated groups decreased in a dose-dependent manner from the control value of 8.2+/-0.14 x 10(8) to 5.31+/-0.15 x 10(8). Since a positive correlation (r=0.95; n=24) was observed between sperm count and DNA content of the epididymal sperm, DNA content was routinely used as an indicator of sperm count, and the results were expressed in terms of both protein and DNA. There was a significant decline in the activities of superoxide dismutase (40+/-2.17 to 27.1+/-0.76/mg protein and 32.41 to 18.07+/-0.76/mg DNA), catalase (2.49+/-0.13 to 2.03+/-0.05/mg protein and 2.01+/-0.05 to 1.35+/-0.05/mg DNA), glutathione reductase (71.2+/-3.87 to 48+/-1.79/mg protein and 57.58+/-1.52 to 31.94/mg DNA) and glutathione peroxidase (22.4+/-1.43 to 16.9+/-1.57/mg protein and 18.08+/-0.61 to 11.38+/-1.22/mg DNA) while there were increases in the levels of hydrogen peroxide (20.8+/-1.96 to 55.3+/-0.88/ mg protein and 16.18+/-1.88 to 36.87+/-0.88/ mg DNA) and lipid peroxidation (2.17+/-0.2 to 6.08/mg protein and 1.75+/-0.12 to 4.05+/-0.12/mg DNA) in the epididymal sperm. The results suggest that graded doses of TCDD elicit depletion of antioxidant defense system in sperm, indicating TCDD-induced oxidative stress in the epididymal sperm. In conclusion, the adverse effect on male reproduction in TCDD-treated rats may be due to the induction of oxidative stress in sperm.     

Hepatocarcinogenesis in female Sprague-Dawley rats following discontinuous treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin.

In this study, we investigated the time course of promotion of tumors and putatively preneoplastic altered hepatic foci in the livers of diethylnitrosamine (DEN)-initiated female Sprague-Dawley rats. These rats had been treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) under different dosing regimens, but we used the same administered biweekly dose of 1.75 microg/kg of body weight. Animals were treated continuously for up to 60 weeks, or continuously for 30 weeks, followed by cessation of treatment for up to 30 weeks. In addition, TCDD treatment in these groups was begun either 2 or 18 weeks after initiation with DEN. Liver tumors were only observed in animals after 60 weeks on the study and were increased by continuous TCDD treatment, relative to controls. The incidence of hepatocellular adenoma and carcinoma combined, in animals treated with TCDD for 30 weeks followed by no TCDD treatment for 30 weeks (17%), was lower than in animals receiving either TCDD (79%) or vehicle control (corn oil) alone (55%) for 60 weeks. The lower liver-tumor incidence after cessation of TCDD treatment paralleled time-dependent decreases in the volume fraction occupied by placental glutathione S-transferase-positive altered hepatic foci and the number of foci per unit volume, but not the mean focus volume that exhibited a time-dependent increase after cessation of TCDD treatment. Cessation of TCDD treatment led to reductions in liver TCDD levels, and these changes were reflected in a cessation of reduced body weight because of TCDD treatment. These data indicate that liver-tumor promotion by TCDD in female rats is dependent upon continuous exposure to TCDD, and that alterations in patterns of TCDD exposure can have significant effects on tumor incidence not reflected by standard measures of dioxin exposure.     

Effects of diphenyl diselenide on lipid profile and hepatic oxidative stress parameters in ovariectomized female rats

Objectives Ovarian hormone decline after menopause is linked to many pathophysiological reactions. Female rats submitted to ovariectomy are employed as a model of post‐menopausal condition. This study investigated the effects of diphenyl diselenide (PhSe)₂ on body weight gain, intra‐abdominal fat deposition, plasma lipid profile and hepatic oxidative stress in ovariectomized rats. Methods Female adult Wistar rats were ovariectomized (OVX rats) or sham‐operated and divided into four groups: (i) sham‐operated, (ii) (PhSe)₂, (iii) OVX and (iv) OVX + (PhSe)₂. (PhSe)₂ (5 mg/kg; 5 ml/kg, p.o.) was administered once a day for 30 days to groups (ii) and (iv). After that, rats were anaesthetized for blood sample gathering and submitted to euthanasia. Key findings (PhSe)₂ (5 mg/kg) was effective in preventing the rise in body weight gain and intra‐abdominal fat deposition induced in OVX rats. Although (PhSe)₂ was not effective in avoiding the increase in plasma total cholesterol and non‐HDL levels induced in OVX rats, (PhSe)₂ reduced plasma triglycerides and augmented HDL levels in OVX rats. (PhSe)₂ also increased hepatic ascorbic acid levels, reduced glutathione content, glutathione S‐transferase activity and restored catalase activity in liver of OVX rats. Conclusions These findings suggest that (PhSe)₂ could be a promising alternative to minimize menopause related symptoms.     

Protective effects of antioxidants on acrylonitrile‐induced oxidative stress in female F344 rats

The induction of oxidative stress and damage appears to be involved in acrylonitrile induction of brain astrocytomas in rat. The present study examined the effects of dietary antioxidant supplementation on acrylonitrile‐induced oxidative stress and oxidative damage in rats in vivo. To assess the effects of antioxidants on biomarkers of acrylonitrile‐induced oxidative stress, female F344 rats were provided with diets containing vitamin E (0.05%), green tea polyphenols (GTP, 0.4%), N‐acetyl cysteine (NAC, 0.3%), sodium selenite (0.1mg/kg), and taurine (10g/kg) for 7 days, and then co‐administered with 0 and 100 ppm acrylonitrile in drinking water for 28 days. Significant increase in oxidative DNA damage in brain, evidenced by elevated 8OHdG levels, was seen in acrylonitrile‐exposed rats. Supplementation with vitamin E, GTP, and NAC reduced acrylonitrile‐induced oxidative DNA damage in brain while no protective effects were seen with the selenium or taurine supplementation. Acrylonitrile increased oxidative DNA damage, measured by the fpg‐modified alkaline Comet assay in rat WBCs, which was reduced by supplementation of Vitamin E, GTP, NAC, selenium, and taurine. In addition to stimulation of oxidative DNA damage, acrylonitrile triggered induction of pro‐inflammatory cytokines Tnfα, Il‐1β, and Ccl2, and the growth stimulatory cyclin D1 and cyclin D2 genes, which were effectively down‐regulated with antioxidant treatment. Antioxidant treatment also was able to stimulate the pro‐apoptotic genes Bad, Bax, and FasL and DNA repair genes Xrcc6 and Gadd45α. The results of this study support the involvement of oxidative stress in the development of acrylonitrile‐induced astrocytomas and suggest that antioxidants block acrylonitrile‐mediated damage through mechanisms that may involve in the suppression of inflammatory responses, inhibition of cell proliferation and stimulation of apoptosis. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1808–1818, 2016.     

Regulation of 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced tumor promotion by 17 beta-estradiol in female Sprague--Dawley rats

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a potent hepatocarcinogen in female but not in male rats. In an initiation-promotion model, ovariectomy inhibits TCDD-induced cell replication and reduces both TCDD-induced tumor formation and the promotion of enzyme-altered hepatocellular foci (AHF). The aim of this study was to determine the involvement of the ovarian hormone 17 beta-estradiol in the induction of cell proliferation and development of putative preneoplastic AHF following chronic exposure to TCDD. Diethylnitrosamine (DEN)-initiated ovariectomized (OVX) female rats were treated with TCDD for 20 or 30 weeks in the presence and absence of 17 beta-estradiol administered continuously by implanted 90-day release pellets. Following 20 weeks of treatment, cell proliferation in TCDD-treated rats was decreased regardless of ovarian hormones. Following 30 weeks of exposureTCDD, only significantly induced cell proliferation in OVX rats receiving supplemental 17 beta-estradiol. These data demonstrate that the the transitory mitoinhibition of cell replication by TCDD is not hormonally responsive, but that induction of cell replication at later time points is. TCDD exposure resulted in elevated AHF expressing gamma-glutamyltranspeptidase (GGT) in intact, but not OVX rats at both time points. TCDD also induced GGT-positive AHF in 17 beta-estradiol-supplemented OVX rats. TCDD induced AHF expressing the placental form of glutathione-S-transferase (PGST) in both intact and OVX rats regardless of 17 beta-estradiol exposure, indicating that the modulating effect of 17 beta-estradiol on AHF was specific to the GGT-positive phenotype.     

N-acetylcysteine attenuates dimethylnitrosamine induced oxidative stress in rats

Oxidative stress has been implicated in the pathogenesis and progression of various hepatic disorders and hence screening for a good hepatoprotective and antioxidant agent is the need of the hour. The present study was aimed to investigate the hepatoprotective and antioxidant property of N-acetylcysteine (NAC) against dimethylnitrosamine (DMN) induced oxidative stress and hepatocellular damage in male Wistar albino rats. Administration of single dose of DMN (5 mg/kg b.w.; i.p.) resulted in significant elevation in the levels of serum aspartate transaminase and alanine transaminase, indicating hepatocellular damage. Oxidative stress induced by DMN treatment was confirmed by an elevation in the status of lipid peroxidation (LPO) and reduction in the activities of enzymic antioxidants such as superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glutathione-S-transferase and in the levels of non-enzymic antioxidants, reduced glutathione, vitamin-C and vitamin-E in the liver tissue. DMN induced oxidative stress and hepatocellular membrane instability was further substantiated by a decline in the status of the membrane bound ATPases in the liver tissue. Post-treatment with NAC (50 mg/kg b.w.; p.o.) for 7 days effectively protected against the DMN induced insult to liver by preventing the elevation in the status of the serum marker enzymes and LPO, and restoring the activities of both the enzymic and non-enzymic antioxidants and membrane bound ATPases towards normalcy. These results demonstrate that NAC acts as a good hepatoprotective and antioxidant agent in attenuating DMN induced oxidative stress and hepatocellular damage.     

Acrylamide-induced oxidative stress and biochemical perturbations in rats

Acrylamide is neurotoxic to experimental animals and humans. Also, it has mutagenic and carcinogenic effects. The present study was carried out to investigate the effects of different doses of acrylamide on some enzyme activities and lipid peroxidation in male rats. Animals were assigned at random to one of the following treatments: group 1 served as control, while groups 2, 3, 4, 5, 6 and 7 were treated with 0.5, 5, 25, 50, 250 and 500 microg/kg body weight of acrylamide, respectively in drinking water for 10 weeks. Acrylamide significantly decreased plasma protein levels and the activity of creatine kinase, while increased plasma phosphatases. The activities of transaminases and phosphatases were significantly decreased in liver and testes, while lactate dehydrogenase did not change compared to control group. Plasma and brain acetylcholinesterase activity was significantly decreased. The concentration of thiobarbituric acid reactive substances, and the activities of glutathione S-transferase and superoxide dismutase in plasma, liver, testes, brain, and kidney were increased in acrylamide-treated rats. On the other hand, results obtained showed that acrylamide significantly reduced the content of sulfhydryl groups and protein in different tissues. The present results showed that different doses of acrylamide exerted deterioration effects on enzyme activities and lipid peroxidation in a dose-dependent manner.     

Crocin attenuates cisplatin-induced renal oxidative stress in rats

Reactive oxygen species (ROS) and oxidative damage are the most important factors in cisplatin-induced acute renal failure. This study examined the protective effects of crocin against cisplatin-induced renal oxidative stress in rat. Animals were divided into five groups (n = 6). Group 1 received normal saline (2 ml/day, i.p.). Group 2 received a single dose of cisplatin (5 mg/kg, i.p.). Groups 3–5 received crocin (100, 200, and 400 mg/kg, i.p., respectively) for four consecutive days beginning 1-h before a single dose of cisplatin (5 mg/kg) on day 1. On day 5, blood samples were drawn and kidneys were removed for histopathological, biochemical and RT-PCR examinations. Twenty four hours urinary chemistries were measured. Blood urea and creatinine and urinary glucose and protein concentrations in crocin-treated groups were significantly lower compared to the cisplatin-treated group. Histopathological studies showed massive damage in the S₃ segment of proximal tubules in cisplatin-treated group but not in crocin-treated groups. Crocin treatment resulted in a significant reduction in malondialdehyde (MDA) concentration and produced a significant elevation in total thiol and glutathione peroxidase concentrations. There was a significant elevation in the mRNA expression of glutathione peroxidase in crocin-treated groups. The results suggest that crocin attenuates cisplatin-induced renal oxidative stress in rats.     

Diazinon-induced oxidative stress and renal dysfunction in rats

Diazinon (O,O-diethyl-O-[2-isopropyl-6-methyl-4-pyrimidinyl] phosphoro thioate), an organo-phosphate insecticide, has been used worldwide in agriculture and domestic for several years, which has led to a variety of negative effects in non target species including humans. However, its nephrotoxic effects and mechanism of action has not been fully elucidated so far. Therefore, the present study was aimed at evaluating the nephrotoxic effects of diazinon and its mechanism of action with special reference to its possible ROS generating potential in rats. Treatment of rats with diazinon significantly enhances renal lipid peroxidation which is accompanied by a decrease in the activities of renal antioxidant enzymes (e.g. catalase, glutathione peroxidise, glutathione reductase, glucose-6-phosphate dehydrogenase, glutathione S-transferase) and depletion in the level of glutathione reduced. In contrast, the activities of renal γ-glutamyl transpeptidase and quinone reductase were increased. Parallel to these changes, diazinon treatment enhances renal damage as evidenced by sharp increase in blood urea nitrogen and serum creatinine. Additionally, the impairment of renal function corresponds histopathologically. In summary, our results indicate that diazinon treatment eventuates in decreased renal glutathione reduced, a fall in the activities of antioxidant enzymes including the enzymes involved in glutathione metabolism and excessive production of oxidants with concomitant renal damage, all of which are involved in the cascade of events leading to diazinon-mediated renal oxidative stress and toxicity. We concluded that in diazinon exposure, depletion of antioxidant enzymes is accompanied by induction of oxidative stress that might be beneficial in monitoring diazinon toxicity.     

Pyritinol reduces nociception and oxidative stress in diabetic rats

The purpose of this study was to assess the antinociceptive and antiallodynic effect of pyritinol as well as its possible mechanism of action in diabetic rats. Streptozotocin (50 mg/kg) injection caused hyperglycemia within 1 week. Formalin-evoked flinching was increased in diabetic rats as compared to non-diabetic rats. Oral acute administration of pyritinol (50-200 mg/kg) dose-dependently reduced flinching behavior in diabetic rats. Moreover, prolonged administration of pyritinol (12.5-50 mg/kg, every 2 days for 2 weeks) reduced formalin-induced nociception. 1H-[1,2,4]-oxadiazolo [4,3-a] quinoxalin-1-one (ODQ, a guanylyl cyclase inhibitor, 2 mg/kg, i.p.), but not naltrexone (a non-selective opioid receptor antagonist, 1 mg/kg, s.c.) or indomethacin (a non-selective cycloxygenase inhibitor, 5 mg/kg, i.p.), blocked the pyritinol-induced antinociception in diabetic rats. Given alone ODQ, naltrexone or indomethacin did not modify formalin-induced nociception in diabetic rats. Oral acute (200 mg/kg) or prolonged (25 mg/kg, every 2 days for 2 weeks) administration of pyritinol significantly reduced streptozotocin-induced changes in free carbonyls, dityrosine, malondialdehyde and advanced oxidative protein products. Four to 8 weeks after diabetes induction, tactile allodynia was observed in the streptozotocin-injected rats. On this condition, oral administration of pyritinol (50-200 mg/kg) reduced tactile allodynia in diabetic rats. Results indicate that pyritinol is able to reduce formalin-induced nociception and tactile allodynia in streptozotocin-injected rats. In addition, data suggest that activation of guanylyl cyclase and the scavenger properties of pyritinol, but not improvement in glucose levels, play an important role in these effects.     

Parachlorophenylalanine exacerbates oxidative stress induced by gentamicin in rats

The present work studies the effect of parachlorophenylalanine (PCPA, 200 mg/kg intraperitoneally/48 hr for 7 days) on the oxidative stress and nephropathy induced by gentamicin (80 mg/kg intraperitoneally/daily for 7 days) in Wistar rats. The effect of PCPA on lipid peroxidation products and reduced glutathione content in renal and brain tissue, as well as on 5HT content in brain was assessed. Catalase and superoxide dismutase activities were determined in brain tissue. Blood urea nitrogen and creatinine in plasma and total protein content in urine were also measured. Gentamicin caused significant increases in proteinuria, non-protein nitrogen compounds and lipid peroxidation markers, together with decreases in both reduced glutathione content in renal and brain tissue and enzymatic activities in brain homogenates. PCPA harnessed the effect of gentamicin in the brain and the kidney, while PCPA alone induced brain oxidative stress. These results support the prooxidant action of PCPA in brain tissue and its capacity to exacerbate the oxidative stress and renal dysfunction induced by gentamicin, as well as the possible antioxidant property of serotonin.     

Melatonin attenuates gentamicin-induced nephrotoxicity and oxidative stress in rats

The present study investigated the protective effects of melatonin (MT) against gentamicin (GM)-induced nephrotoxicity and oxidative stress in rats. We also investigated the effects of MT on induction of apoptotic cell death and its potential mechanisms in renal tissues in response to GM treatment. The following four experimental groups were evaluated: (1) vehicle control, (2) MT (15?mg/kg/day), (3) GM (100?mg/kg/day), and (4) GM&MT. GM caused severe nephrotoxicity as evidenced by increased serum blood urea nitrogen and creatinine levels, increased renal tubular cell apoptosis, and increased Bcl2-associated X protein and cleaved caspase-3 protein expression. Additionally, GM treatment caused an increase in levels of inducible nitric oxide synthase (iNOS) and nuclear factor-kappa B (NF-κB) protein expression in renal tissues. The significant decreases in glutathione content, catalase, superoxide dismutase, glutathione-S-transferase, glutathione peroxidase, and glutathione reductase activities and the increase in malondialdehyde content indicated that GM-induced tissue injury was mediated through oxidative reactions. In contrast, MT treatment protected kidney tissue against the oxidative damage and the nephrotoxic effect caused by the GM treatment. Histopathological studies confirmed the renoprotective effect of MT. These results indicate that MT prevents nephrotoxicity induced by GM in rats, presumably because it is a potent antioxidant, restores antioxidant enzyme activity, and blocks NF-κB and iNOS activation in rat kidney.     

2,3,7,8-Tetrachlorodibenzo-p-dioxin-induced change in intestinal function and pathology: evidence for the involvement of arylhydrocarbon receptor-mediated alteration of glucose transportation

Although numerous studies have been performed to clarify the mechanism(s) underlying the toxicological responses induced by dioxins, their effect on the intestine is less well understood. To address this issue, we examined the effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the pathology and function of the intestine in arylhydrocarbon receptor (AhR)-sensitive (C57BL/6J) and -less-sensitive (DBA/2J) mice. A single oral administration of TCDD (100 mug/kg) to C57BL/6J mice produced changes in villous structure and nuclear/cytoplasm ratio in the epithelial cells of the intestine. Furthermore, in an oral glucose tolerance test, the serum glucose level was significantly increased in the C57BL/6J mouse but not in the DBA/2J mouse by TCDD treatment. In agreement with this, the expression of intestinal mRNAs coding sodium-glucose co-transporter 1 (SGLT1) and glucose transporter type 2 were increased only in C57BL/6J mice by TCDD. The increase in the former transporter was also confirmed from its protein level. The glucose level in the intestinal contents is thought to be one of the factors contributing to SGLT1 induction. Concerning with this, the intestinal activity of sucrase and lactase was significantly increased only in C57BL/6J mice by TCDD. These results suggest that while TCDD produces initial damage to the intestinal epithelium, the tissues induce SGLT1 to facilitate the absorption of glucose, which is expected, at least partially, to combat the wasting syndrome induced by TCDD. The data provided here also suggest that AhR is involved in the mechanism of SGLT1 induction.     

Pesticides induced oxidative stress and female infertility: a review

Abstract

Oxidative stress impairs the female reproductive physiology by altering the affectivity of antioxidant defense system in the individual. Several toxicants mainly pesticides alters this defense system producing various lifestyle-related diseases. The imbalance in antioxidant defense system, due to pesticidal toxicity-induced oxidative stress, is found to be associated with reproductive disorders like estrous cycle defects, impaired folliculogenesis, follicular atresia, implantation defects, spontaneous abortions, endometriosis, fetal, and other birth defects, thereby, directly affecting fertility and reproductive physiology of the organism. So, the present review emphasizes upon pesticides-mediated oxidative stress and its influence on female fertility.