Antioxidant Defense System In Rats Research Articles

Protective role of buffalo pineal proteins on arsenic-induced oxidative stress in blood and kidney of rats

Objective: Exposure to various toxic metals has become an increasingly recognized source of ill- ness in human and animals, worldwide. Arsenic (As) and its compounds cause adverse health effects in animals and humans. Recently, it has been suggested that the pineal gland may also have antioxidants role due to secretary product other than melatonin. With keeping this view, pre-sent investigation tested effect of buffalo (Bubalus bubalis) pineal proteins (PP) on arsenic-induced oxidative stress in RBCs (Red blood cells) and kidney of rats. Methods: Eighteen adult female Wistar rats were grouped into group-I (Control), group-II (Arsenic control), and group-III (Arsenic + Pineal proteins). Experimental rats were given 100 ppm arsenic (p.o.) for 4 weeks alone or along with pineal proteins at a dose of 100 µg/kg body weight (i.p.). Results: Interestingly, arsenic ex-posure led to the stimulation of kidney catalase (CAT) activity, but inhibition of RBCs CAT activ-ity and significantly (P<0.05) increased the RBCs and kidney lipid peroxidation level (LPO). How-ever, arsenic treatment caused depletion of glu- tathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione reductase (GR) in kidney tissues. In RBCs, only GR and CAT activity were significantly (P<0.05) declined. These changes were significantly (P<0.05) reversed by PP treatment in arsenic exposed animals. Conclusion: Therefore, present study indicated the significant protecting effect of buf-falo (Bubalus bubalis) PP against arsenic in-duced-oxidative stress through antioxidant de-fense systems in rats.

Pre-weaning undernutrition alters the expression levels of reactive oxygen species enzymes but not their activity levels or lipid peroxidation in the rat brain

It has been hypothesised that the increased life span commonly observed in rodents that have had their diet restricted after weaning may be related to its effects on the anti-oxidant defence systems. However, undernutrition during the gestation and pre-weaning period is known to have long-term deleterious effects on a rodent's growth and development, and it has been suggested that this may reduce their life span. We have now examined some of the anti-oxidant defence system in rats that have been undernourished from conception until 21 postnatal days-of-age, followed in some cases by a period of nutritional rehabilitation until 62 days of age. We found that such undernutrition could modulate the mRNA expression of Cu/ZnSOD and catalase in some brain regions. However, only catalase showed any undernutrition-induced change of enzyme activity level. There was some evidence that undernourished (but not control) rats had an age-related increase in the level of lipid peroxidation between 21 and 62 days of age, although the group × age interaction was not statistically significant. There was no significant change in the level of reduced glutathione induced by the pre-weaning period of undernutrition. If ROS and the extent of oxidative damage are truly implicated in the determination of life span, our results indicate that this is unlikely to be markedly affected by the relatively small changes we have observed in the anti-oxidant defence systems induced by undernutrition of rats from conception until weaning.

Protective effect of zinc supplementation on blood antioxidant defense system in rats exposed to cadmium

The aim of this study was to assess the effects of subchronic exposure to cadmium (Cd) on the antioxidant defense system of red blood cells (RBCs) and lipid peroxide concentration in the plasma, as well as the possible protective role of zinc (Zn). For this purpose, 60 male Wistar rats (8 weeks old) were divided into three groups: the first group was exposed to Cd in the form of CdCl 2, administered in five doses (each of 0.4 mg Cd/kg BW) on days 5, 10, 15, 20 and 25, giving a total dose of 2 mg Cd/kg BW, i.p.; the second group was simultaneously exposed to Zn and Cd with the same timeline and the same doses of Cd as the first group but with, in addition, injections of Zn in the form of ZnCl 2, administered in doses of 0.8 mg Zn/kg BW, giving a total dose of 4 mg Zn/kg BW, i.p.; a control group received 0.5 mL of physiological saline in an identical manner. It was shown that exposure to Cd induced a significant decrease ( p<0.05) in superoxide dismutase (Zn/Cu SOD) and catalase (CAT) activities in RBCs. Increased lipid peroxide concentration, measured by thiobarbituric acid reactive substances (TBARS), was also observed in the plasma of cadmium-exposed rats. Cd had no effect on glutathione peroxidase (GSH-Px) activity. Zn administration had a beneficial effect on the Cd-induced decrease in Zn/Cu SOD activity ( p<0.05) but not on CAT activity. Animals receiving Cd and Zn simultaneously had significantly ( p<0.05) lower concentrations of lipid peroxides than rats exposed to Cd alone. Our results indicate that Cd causes oxidative stress and that Zn supply in conditions of exposure to Cd can partially protect against Cd-induced oxidative stress.

Effect of Fish Oil, Olive Oil, and Vitamin E on Liver Pathology, Cell Proliferation, and Antioxidant Defense System in Rats Subjected to Partial Hepatectomy

The high capacity of liver regeneration after partial hepatectomy (PH) is well known. This study investigated the role of the antioxidant defense system in regeneration among Wistar-albino male rats subjected to 70% partial hepatectomy after a pretreatment period of 2 weeks with eicosapentanoic acid (EPA) rich fish oil (FO), first pressed virgin olive oil (OO), or vitamin E. The control group of 10 rats underwent PH only. On postoperative day 3, all rats were humanely killed. Liver sections of animals treated with FO or vitamin E showed significant increases in regeneration within both liver parenchyma and cut surface compared with the control group ( P < .05). Liver sections of OO displayed an insignificant increase in liver regeneration ( P > .05), with less increase in parenchyma than of the cut surface. The enhancement of the liver parenchymal regeneration in the FO group was significantly greater than that of the vitamin E group. Concerning liver function tests (LFT), there was no significant difference among the groups. When the treatment groups were compared to the control group glutathione (GSH) levels were increased and content of malondialdehyde (MDA), nitric oxide (NO), and superoxide dismutase (SOD) were decreased. Based on these results, we concluded that after 70% PH in rats, the liver parenchyma and cut surface regeneration were greatest with FO and least with OO treatment. Both FO and vitamin E served to improve the antioxidant defense system more than OO treatment.

Impact of polychlorinated biphenyl Aroclor 1254 on testicular antioxidant system in adult rats

To clarify the reproductive toxicity of polychlorinated biphenyl compounds through determination of testicular lipid peroxidation, reactive oxygen species and enzymatic and non-enzymatic antioxidants in rats exposed to Aroclor 1254. Adult male rats were administered Aroclor 1254 at a dose of 2 mg/kg per day ip for 30 days. The rats were sacrificed 24 hours after last dosing and the serum and other tissues collected and processed for relevant determinations. The body weight and the weights of the testis, epididymis, ventral prostate and seminal vesicle and the serum testosterone and estradiol were significantly decreased in Aroclor 1254 treated rats. The testicular lipid peroxidation, hydrogen peroxide and hydroxyl radical were significantly elevated whereas, testicular antioxidant enzymes, including superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), glutathione-S-transferase (GST) and glutathione reductase (GR) were significantly decreased. The non-enzymatic antioxidants, vitamin C and vitamin E, were also decreased. These results suggest that Aroclor 1254 induces an increase in the lipid peroxidation, hydrogen peroxide and hydroxyl radical and diminish in the antioxidant defense system in rats, indicating that the free radical-dependent mechanism may play an important role in the testicular toxicity of polychlorinated biphenyls.

Effect of Oren-gedoku-to (Huanglian-Jie-Du-Tang) extract on disruption of hepatic antioxidant defense systems in rats treated with d-galactosamine

We have indicated that the antioxidant action of Oren-gedoku-to (Huanglian-Jie-Du-Tang) extract (TJ-15), a traditional Chinese herbal medicine, may contribute to its preventive effect on the progression of d-galactosamine (GAL)-induced liver injury in rats. Herein, we examined a possibility that TJ-15 exerts this preventive effect by attenuating the disruption of hepatic antioxidant defense systems in GAL-treated rats. TJ-15 (500 mg/kg) was orally administered to rats injected with GAL (500 mg/kg, i.p.) at 6 h after hepatotoxin treatment. In the liver of rats treated with GAL alone, the concentration of thiobarbituric acid-reactive substances (TBARS), an index of lipid peroxidation, increased at 24 h, but not at 6 h, while reduced glutathione (GSH) and ascorbic acid concentrations and superoxide dismutase (SOD), catalase, and Se-glutathione peroxidase (Se-GSH-px) activities decreased at 24 h, but not at 6 h. Post-administered TJ-15 prevented all these changes observed at 24 h after GAL treatment. TJ-15 administered to GAL-untreated rats in the same manner did not affect the hepatic TBARS, GSH, and ascorbic acid concentrations and SOD, catalase, and Se-GSH-px activities. These results indicate that post-administered TJ-15 attenuates the disruption of hepatic antioxidant defense systems in GAL-treated rats, which may contribute to its preventive effect on the progression of GAL-induced liver injury.

Dietary oxidized cholesterol increases expression and activity of antioxidative enzymes and reduces the concentration of glutathione in the liver of rats.

An experiment was conducted with rats to investigate the effect of dietary oxidized cholesterol on the antioxidant status. Four groups of male, growing Sprague-Dawley rats received diets containing unoxidized or oxidized cholesterol (5 g/kg diet) with either coconut oil or salmon oil as dietary fat (100 g/kg diet) for 5 weeks. The oxidized cholesterol preparation consisted of 7 g of various cholesterol oxidation products and 93 g of unmodified cholesterol per 100 g preparation. No significant amounts of oxysterols were detected in the unoxidized cholesterol-supplemented diets. As parameters of the antioxidant status activities, mRNA concentrations of several antioxidative enzymes and the concentrations of glutathione were measured. Rats fed the diets containing oxidized cholesterol had significantly higher mRNA concentrations of glutathione peroxidase (p < 0.001) and superoxide dismutase (p < 0.01), a significantly higher activity of glutathione peroxidase (p < 0.001), and significantly lower concentrations of total (p < 0.05) and reduced glutathione (p < 0.01) in the liver than rats fed diets containing unoxidized cholesterol. These effects were independent of the dietary fat. In conclusion, the study suggests that dietary oxidized cholesterol stresses the antioxidant defense system in rats.

Effect of oxalomalate on lipid metabolism and antioxidant defense system in rats.

The metabolic functions of NADP(+)-specific isocitrate dehydrogenase (ID2), which may participate in the production of NADPH and biosynthesis of fatty acids, are not yet clearly understood. Accordingly, the current study investigated the effect of oxalomalate, known as a competitive inhibitor of ID2 in vitro, on lipid metabolism and the cellular defense system in vivo. Male Sprague Dawley rats (3 weeks old) were divided into two groups, fed a pelletized AIN-76 semisynthetic diet for 8 weeks, and injected intraperioneally with either saline or oxalomalate (25 mg/kg BW) dissolved in saline every 2 days. Oxalomalate did not lower the body weight and adipose tissue weight significantly; however, it significantly lower the plasma leptin concentration (p < 0.000), plasma and hepatic triglyceride levels (p < 0.01, p < 0.05), and adipocyte lipoprotein lipase activity (p < 0.01) compared to the control group. Meanwhile, hepatic antioxidant enzyme activities, except for superoxide dismutase activity (p < 0.01), glutathione content, and thiobarbituric acid reactive substances levels were not significantly different between the groups. Therefore, the current data suggests that oxalomalate produces a triglyceride-lowering activity and play a possible inhibitory role in fat accumulation. Furthermore, it was not found to affect the most antioxidative enzyme activities, glutathione content, and thiobarbituric acid reactive substances levels in rats fed normal diet.

INTERACTION OF EXERCISE TRAINING WITH ETHANOL AND THEOPHYLLINE ON CARDIAC ANTIOXIDANT DEFENSE SYSTEM IN RATS

Earlier studies from our laboratory have shown that exercise training for 6.5 to 10 weeks up-regulated the cardiac antioxidant system and attenuated alcohol-induced oxidative injury in rat heart. Since many individuals perform regular exercise and also consume alcoholic and/or methylxanthine containing beverages, therefore, the objective of this study was to investigate the effects of exercise training (Ex) and its interaction with chronic low dose ethanol (Et) and theophylline (Th) administration on cardiac antioxidant defense system in rats. Male Fisher-344 rats were divided into five different groups and treated as follows: (1) Sedentary Control; (2) Exercise; (3) Ex + Et (1g/kg, p.o.); (4) Ex + Th (1.7x10–6 moles/kg, i.p.); and (5) Ex + Et + Th. The animals were treated with the drugs and exercised on a treadmill for 6.5 weeks, and physiological parameters such as respiratory exchange ratio (RER), time to reach maximal oxygen consumption (VO2max time), heart rate and blood pressure were recorded every week. The rats were sacrificed 24 hours after the last treatments and hearts were isolated. The results showed a significant effect over time, including a significant linear trend for RER, VO2max time and blood pressure. Total SOD and GSH-Px activities significantly increased (119% and 132% of control) in the heart of Ex plus Et group. Theophylline blocked cardiac SOD and GSH-Px activities induced by Ex and Et. The ratio of GSH-Px/SOD significantly decreased (64% of control) in Ex plus Et plus Th group. It is concluded that theophylline modified the cardiac antioxidant system induced by ethanol and exercise training, which in turn influenced the physiological parameters in rats. Supported by AHA-IL Affiliate 9708751 A

Chronic diarrhea impairs intestinal antioxidant defense system in rats at weaning.

The aim of the present study was to evaluate the influence of severe protein-energy malnutrition on the antioxidant defense system in the small and large intestine in rats at weaning. Chronic diarrhea and the subsequent malnutrition were induced by oral intake of a lactose-enriched diet. Twenty rats were weaned at 21 days of age, and the control group was fed a semipurified synthetic diet for two weeks. The malnourished group was fed the same diet but carbohydrates were replaced by lactose, and they developed diarrhea one day after. Rats were killed, and macroscopic and histological features were analyzed, DNA content was measured, and alkaline phosphatase, myeloperoxidase, and gamma-glutamyltranspeptidase activities were determined to assess the degree of intestinal injury. Glutathione levels as well as the activities of intestinal glutathione transferase, glutathione reductase, total glutathione peroxidase, selenium-dependent glutathione peroxidase, superoxide dismutase, and catalase were measured to study the antioxidant defense system. Malnourished rats showed loss of body weight and an increase in length and weight in jejunum and ileum, while no significant changes were observed in colon. Epithelial cells showed fewer and shorter microvilli, larger mitochondria with low inner density and loss of cristae, dilated endoplasmic reticulum, and Golgi apparatus. The protein-to-DNA ratio was higher in the jejunum, ileum, and colon of malnourished rats. Glutathione levels decreased 40% in jejunum and 50% in colon of malnourished rats. A 40-50% decrease in the activity of all the enzymes of the antioxidant defense system was observed in the jejunum and ileum of malnourished rats, while only catalase and glutathione transferase activities decreased 50% in colon. These results suggest that early chronic diarrhea and severe protein-energy malnutrition impair the antioxidant defense system in both the small and large intestine, which may have a role in the pathogenesis and maintenance of the vicious circle of malabsorption-diarrhea-malnutrition in infancy.

Dose and Time Dependent Effects of Ethanol on Antioxidant System in Rat Testes

This study was designed to investigate the dose as well as time dependent effects of ethanol on testicular antioxidant defense system in rats. Male Fischer 344 rats were administered ethanol at a dose of 2, 4, and 6 gm/kg orally and control received equal volume of saline and sacrificed 1 h after ethanol ingestion. For time course study, animals were administered ethanol 4 g/kg orally and sacrificed at 1.5, 2, 4, and 6 h after ethanol ingestion. Testicular ethanol concentration increased with increasing doses of ethanol. Copper zinc-superoxide dismutase (CuZn-SOD) activity significantly decreased in the testes of rats treated with increasing doses of ethanol whereas manganese-superoxide dismutase (Mn-SOD) activity significantly increased in a dose dependent manner (181, 186, and 195% of control, respectively). Testicular glutathione (GSH) and malondialdehyde (MDA) levels did not significantly alter with increasing doses of ethanol one hour after ethanol ingestion. Ethanol concentration decreased in the testes with an increase in time after ethanol ingestion. Testicular CuZn-SOD activity significantly decreased whereas Mn-SOD activity increased with an increase in time after ethanol ingestion. Testicular catalase (CAT) activity significantly decreased at 2 h postethanol ingestion. Testicular MDA levels significantly increased at 4 and 6 h after ethanol ingestion indicating that end product of lipid peroxidation, MDA, takes considerable time to form in the testes. A significant decrease in the ratios of CAT/Mn-SOD and glutathione peroxidase (GSH-Px)/Mn-SOD in the testes of rat suggests the ability of mitochondria to scavenge reactive oxygen species (ROS). It is suggested that antioxidant enzyme ratios may be used as an important parameter to determine ethanol induced oxidative stress in the tissues.

Effect of HD-03, a herbal formulation, on the antioxidant defence system in rats

The effect of HD-03, a herbal formulation was investigated on the hepatocellular antioxidant defence system in CCl4 treated rats. Three doses of CCl4 were administered orally with liquid paraffin (1:1) to induce hepatic damage. Twenty four hours after the last dose, blood was collected by decapitation for the estimation of serum ALT and AST. The levels of antioxidant enzymes, lipid peroxidation and glycogen in the liver were estimated. Nineteen days pretreatment with HD-03 (750 mg/kg) significantly reversed CCl4-induced changes in serum ALT and AST levels. HD-03 pretreatment also significantly reversed the CCl4-induced changes in the different components of the cellular antioxidant system and lipid peroxidation. Pretreatment with HD-03 significantly restored the hepatic glycogen levels which were depleted in CCl4 intoxicated rats. The observed reversal produced by HD-03 in the serum AST and ALT may be due to the membrane stabilizing potential which helps in preventing the leakage of intracellular enzymes into the systemic circulation. The increase in the hepatic glycogen levels in HD-03 pretreated rats, indicates its preventive effect on subcellular injury caused by CCl4, which leads to glycogenolysis, as a result of disturbance in the intracellular Ca+2 pool. The inhibition of lipid peroxidation and enhancement in the activity of antioxidant enzymes by HD-03 may be due to the direct free radical scavenging activity and reactivation of these enzymes in the liver. Thus the antioxidant potential and inhibitory effect on­lipid peroxidation may play an important role in the antihepatotoxic activity of HD-03. © 1998 John Wiley & Sons, Ltd.

Dietary monounsaturated n-3 and n-6 long-chain polyunsaturated fatty acids affect cellular antioxidant defense system in rats with experimental ulcerative colitis induced by trinitrobenzene sulfonic acid.

The intrarectal administration of trinitrobenzene sulfonic acid in rats induces ulcerative colitis, which results in histological alterations of colonic mucosa, severe modification of the cellular antioxidant defense system, and enhanced production of inflammatory eicosanoids. This study evaluated the influence of different dietary fatty acids, i.e., monounsaturated, n-3, and n-3 + n-6 polyunsaturated fatty acids, on the recovery of the colonic mucosa histological pattern, the cellular antioxidant defense system of colon, and PGE2 and LTB4 colonic mucosa contents in a model of ulcerative colitis induced by intrarectal administration of trinitrobenzene sulfonic acid. Administration of dietary n-3 polyunsaturated fatty acids led to a minimum stenosis score, a higher histological recovery, lower colon alkaline phosphatase and gamma-glutamyltranspeptidase activities, and lower mucosal levels of PGE2 and LTB4 compared with the other two experimental groups. However, glutathione transferase, glutathione reductase, glutathione peroxidase, and catalase activities were lower in the group treated with n-3 polyunsaturated fatty acids than in the groups fed with either the monounsaturated or the n-6 + n-3 polyunsaturated enriched diet. We conclude that n-3 polyunsaturated fatty acids can be administered to prevent inflammation in ulcerative colitis, but they cause a decrease in the colonic antioxidant defense system, promoting oxidative injury at the site of inflammation.