Effect of carnitine administration on levels of lipid peroxides and activities of superoxide dismutase and catalase in isoproterenol-induced myocardial infarction in rats

The effect of carnitine administration on levels of lipid peroxide and activities of superoxide dismutase and catalase was studied in rats administered isoproterenol to induce myocardial infarction. Levels of fatty acid were lower in rats pretreated with carnitine at the peak period and given isoproterenol than the levels in isoproterenoltreated control rats. Lipid peroxides were decreased in the heart at peak infarction in carnitine-treated rats compared to the levels in isoproterenol-treated controls. Activities of superoxide dismutase and catalase showed no change in carnitine-treated animals given isoproterenol compared to those in normal control rats, while they decreased in animals treated with isoproterenol alone.     

Lipid peroxidation and antioxidant systems in the blood of young rats subjected to chronic fluoride toxicity

Wistar albino rats were exposed to 30 or 100 ppm fluoride in drinking water during their fetal, weanling and post-weaning stages of life up to puberty. Extent of lipid peroxidation and response of the antioxidant systems in red blood cells and plasma to prolonged fluoride exposure were assessed in these rats in comparison to the control rats fed with permissible level (0.5 ppm) of fluoride. Rats treated with 100 ppm fluoride showed enhanced lipid peroxidation as evidenced by elevated malondialdehyde (MDA) levels in red blood cells but, 30 ppm fluoride did not cause any appreciable change in RBC MDA level. 30 ppm fluoride-intake resulted in increased levels of total and reduced glutathione in red blood cells and ascorbic acid in plasma while 100 ppm fluoride resulted in decreases in these levels. The activity of RBC glutathione peroxidase was elevated in both the fluoride-treated groups, more pronounced increase was seen with 100 ppm. Reduced to total glutathione ratio in RBC and uric acid levels in plasma decreased in both the groups. RBC superoxide dismutase activity decreased significantly on high-fluoride treatment. These results suggest that long-term high-fluoride intake at the early developing stages of life enhances oxidative stress in the blood, thereby disturbing the antioxidant defense of rats. Increased oxidative stress could be one of the mediating factors in the pathogenesis of toxic manifestations of fluoride.     

Protective action of aspirin in experimental myocardial infarction induced by isoproterenol in rats and its effect on lipid peroxidation

The protective action of aspirin in experimental myocardial infraction induced by isoproterenol was studied in rats. Aspirin treated rats showed lower mortality rate and smaller changes in the myocardium on histopathological examination when compared to corresponding animals given isoproterenol alone. Changes were also observed in the different lipid fractions studied. The ratio of cholesterol to phospholipids decreased in the heart in aspirin treated animals when compared to control rats given isoproterenol alone. The levels of lipid peroxide also showed a decrease while the activity of superoxide dismutase (SOD) and catalase registered an increase in the aspirin treated animals given isoproterenol when compared to corresponding animals given isoproterenol alone.     

Effects of corticosterone and 2,3,7,8‐tetrachloro‐ dibenzo‐p‐dioxin on epididymal antioxidant system in adult rats

2,3,7,8‐Tetrachlorodibenzo‐p‐dioxin (TCDD), an endocrine disruptor, causes epididymal toxicity by inducing oxidative stress. Glucocorticoids have been found to influence TCDD action in vitro and in vivo. The present experiments were set up to analyze the effects of TCDD on rat epididymal antioxidant system under the influence of increased corticosterone level. Adult male Wistar/NIN rats (70–80 days old) numbering 24 (six per group) were used in the study. Corticosterone (3 mg/kg body weight per day) or TCDD (100 ng/kg body weight per day) were administered or coadministered to rats for 15 days. Treatment with corticosterone or TCDD decreased the levels of serum testosterone significantly. In caput, corpus, and cauda fractions, administration of corticosterone or TCDD increased the levels of lipid peroxidation and hydrogen peroxide and decreased the activities of superoxide dismutase and catalase significantly. Coadministration of corticosterone and TCDD to rats decreased the levels of serum testosterone significantly as compared with rats treated with TCDD alone. In caput, corpus, and cauda fractions, the levels of lipid peroxidation and hydrogen peroxide were increased and activities of superoxide dismutase and catalase were decreased significantly as compared with rats treated with TCDD alone. Stress, characterized by increased glucocorticoid levels and activity, may enhance TCDD‐induced epididymal toxicity. © 2010 Wiley Periodicals, Inc. J Biochem Mol Toxicol 24:242–249, 2010; View this article online at wileyonlinelibrary.com . DOI 10.1002/jbt.20332     

Effect of lead acetate on superoxide anion generation and its scavengers in mice given endotoxin

The administration of endotoxin to mice rendered hypersensitive by lead acetate resulted in profound lipid peroxide formation in the liver 6 hr postintoxication. Endotoxin plus lead acetate administration depressed glutathione peroxidase and superoxide dismutase activities in mouse liver, whereas superoxide anion generation significantly increased in the livers of endotoxin plus lead acetate-treated mice compared with that in mice treated with endotoxin alone. Serum acid phosphatase and lactate dehydrogenase isozyme exhibited much more leakage in endotoxin plus lead acetate-injected mice than in sera of mice given endotoxin alone. Nonprotein SH level in the liver was reduced markedly in endotoxin-lead treated mice compared with those receiving endotoxin alone. The plasma vitamin E level was found to decline by 6 hr postintoxication in both endotoxin-lead and endotoxin alone-treated mice, and the transient elevation of the plasma level at 18 hr may be considered to indicate mobilization from other tissues into the blood.     

Effects of Bacillus thuringiensis toxin on hepatic lipid peroxidation and free-radical scavengers in rats given alpha-tocopherol or acetylsalicylate

The effect of Dipel (D), a Bacillus thuringiensis-based bioinsecticide, on hepatic antioxidant enzyme activities and lipid peroxidation in rat liver was investigated. Administration of D in a dose of 1 mg/100 g body mass for 4 successive days increased the activities of glutathione peroxidase (GPx), glutathione reductase (GR) and the level of malondialdehyde (MDA) in rat hepatocytes. The activity of superoxide dismutase (SOD) and glutathione (GSH) level were decreased. Administration of D in rats pretreated with alpha-tocopherol (alphaT) or acetylsalicylic acid (ASA) decreased the activities of GPx, GR and MDA levels, while the GSH level was increased compared with rats treated with D alone. The SOD activity was increased in rats pretreated with alphaT before D, but decreased on pretreatment with ASA, compared with rats treated with D alone. The results indicated that D induced oxidative stress in rat liver that has been protected by prior administration of alphaT or ASA.     

Restoration of antioxidants in liver by methionine feeding in experimental rat urolithiasis.

The effect of methionine or citrate on antioxidant defense system has been studied in urolithic rat. Liver weight and its protein concentration did not change in the rats fed with calculi producing diet (CPD) when compared to normal diet fed rats. Feeding rats along with citrate (c-CPD) or methionine (m-CPD) improved their body weight gain. Liver microsomes and mitochondria fractions of CPD and c-CPD fed groups showed increased susceptibility for lipid peroxidation in presence of ascorbate and t-butyl hydroperoxide when compared to either control or m-CPD fed groups. Increased superoxide dismutase and xanthine oxidase activities, decreased catalase, glutathione peroxidase and glucose-6-phosphate dehydrogenase activities, decreased concentrations of reduced glutathione, total thiols, ascorbic acid and vitamin-E and increased formation of hydroxyl radical, hydroperoxides and diene conjugates were observed in the liver of both CPD fed group as well as c-CPD fed group. Except SOD and xanthine oxidase, all other parameters were normalized in m-CPD fed group. This suggested that feeding methionine reduced the susceptibility for lipid peroxidation by restoration of the level of free radical scavengers.     

Short-term gemfibrozil treatment reverses lipid profile and peroxidation but does not alter blood glucose and tissue antioxidant enzymes in chronically diabetic rats

In this study, we investigated the efficiency of short-term treatment with gemfibrozil in the reversal of diabetes-induced changes on carbohydrate and lipid metabolism, and antioxidant status of aorta. Diabetes was induced by a single injection of streptozotocin (45 mg/kg, i.p.). After 12 weeks of induction of diabetes, the control and diabetic rats were orally gavaged daily with a dosing vehicle alone or with 100 mg/kg of gemfibrozil for 2 weeks. At 14 weeks, there was a significant increase in blood glucose, plasma cholesterol and triglyceride levels of untreated-diabetic animals. Diabetes was associated with a significant increase in thiobarbituric acid reactive substances (TBARS) in both plasma and aortic homogenates, indicating increased lipid peroxidation. Diabetes caused an increase in vascular antioxidant enzyme activity, catalase, indicating existence of excess hydrogen peroxide (H₂O₂). However, superoxide dismutase (SOD) and glutathione peroxidase (GSHPx) activities in aortas did not significantly change in untreated-diabetic rats. In diabetic plus gemfibrozil group both plasma lipids and lipid peroxides showed a significant recovery. Gemfibrozil treatment had no effect on blood glucose, plasma insulin and vessel antioxidant enzyme activity of diabetic animals. Our findings suggest that the beneficial effect of short-term gemfibrozil treatment in reducing lipid peroxidation in diabetic animals does not depend on a change of glucose metabolism and antioxidant status of aorta, but this may be attributed to its decreasing effect on circulating lipids. The ability of short-term gemfibrozil treatment to recovery of metabolism and peroxidation of lipids may be an effective strategy to minimize increased oxidative stress in diabetic plasma and vasculature.     

Effect of a 50 Hz electric field on plasma ACTH, glucose, lactate, and pyruvate levels in stressed rats

The effect of extremely low frequency electric field (EF) on stress induced changes of plasma ACTH, glucose, lactate, and pyruvate levels was examined in ovariectomized rats. The rats were exposed to 50 Hz EF (17500 V/m) for 60 min and were restrained for the latter half (30 min) of the EF exposure period. The restraint stress significantly increased the plasma ACTH and glucose levels (P <.05: Student's t test). Restraint induced increase of plasma ACTH and glucose levels tended to be suppressed by exposure to the EF. Meanwhile, the EF exposure also affected plasma lactate level. Thus, the EF exposure significantly decreases plasma lactate levels in the stressed rats (P <.05: Student's t test). Although the precise mechanisms in the restraint dependent alteration in plasma ACTH, glucose, lactate, and pyruvate levels are not fully understood, our results demonstrate that the 50 Hz EF alter both stress responses and energy metabolism in stressed rats.     

Antioxidant enzymes and lipoperoxide in blood in uremic children and adolescents

To determine whether oxidant-antioxidant balance is altered in chronic renal failure, antioxidant enzymes and lipid peroxide in peripheral blood cells and lipid peroxide in plasma were measured. Nine children and adolescents maintained on hemodialysis (HD), 9 on continuous ambulatory peritoneal dialysis (CAPD), and 14 controls were studied. Lipid peroxide was assayed fluorimetrically as thiobarbituric acid-reactive substances, superoxide dismutases by radioimmunoassays. Both manganese and copper-zinc superoxide dismutases in lymphocytes and monocytes in the HD and CAPD patients, and manganese superoxide dismutase in polymorphs in the HD patients were higher than in the controls. Copper-zinc superoxide dismutase, glutathione peroxidase, and catalase in erythrocytes were unaltered. The lipid peroxide level in plasma in the dialyzed patients was increased, whereas those in polymorphs and lymphocytes were unaltered. Triglyceride and total cholesterol in plasma in the dialyzed patients were also increased. The plasma lipid peroxide in the patients correlated with the triglyceride and total cholesterol level. This is the first study in which manganese superoxide dismutase is measured in nucleated cells of the patients with chronic renal failure. The present results suggest that increased superoxide dismutases protect against oxidative stress induced by chronic renal failure in nucleated cells but in neither erythrocytes nor plasma.     

Oxidative stress in streptozotocin-induced diabetic rats: effects of garlic oil and melatonin

In the present study, oxidative stress in diabetic model and the effect of garlic oil or melatonin treatment were examined. Streptozotocin (60 mg/kg body weight, i.p.)-induced diabetic rats, showed a significant increase of plasma glucose, total lipids, triglyceride, cholesterol, lipid peroxides, nitric oxide and uric acid. Concomitantly, significant decreases in the levels of antioxidants ceruloplasmin, albumin and total thiols were found in the plasma of diabetic rats. Lipid peroxide levels were significantly increased in erythrocyte lysate and in homogenates of liver and kidney, while superoxide dismutase (SOD) activities were decreased in tissue homogenates of liver and kidney. Treatment of diabetic rats with garlic oil (10 mg/kg i.p.) or melatonin (200 microg/kg i.p.) for 15 days significantly increased plasma levels of total thiol, ceruloplasmin activities, albumin. Lipid peroxides, uric acid, blood glucose, total lipid, triglyceride and cholesterol were decreased significantly after treatment with garlic oil or melatonin. Nitric oxide levels were decreased significantly in rats treated with melatonin only. In erythrocytes lysate, glutathione S-transferase (GST) activities were increased significantly in rats treated with garlic oil or melatonin, while lipid peroxides decreased significantly and total thiol increased significantly in melatonin or garlic oil treatment, respectively. In liver homogenates of rats treated with garlic or melatonin, lipid peroxides were decreased significantly, and GST activities increased significantly, while SOD activities were increased significantly in liver and kidney after garlic or melatonin treatment. The results suggest that garlic oil or melatonin may effectively normalize the impaired antioxidants status in streptozotocin induced-diabetes. The effects of these antioxidants of both agents may be useful in delaying the complicated effects of diabetes as retinopathy, nephropathy and neuropathy due to imbalance between free radicals and antioxidant systems. Moreover, melatonin may be more powerful free radical scavenger than garlic oil.     

Protective influences of alpha-ketoglutarate on lipid peroxidation and antioxidant status in ammonium acetate treated rats

The effects of alpha-ketoglutarate on ammonium acetate induced hyperammonemia were studied biochemically in experimental rats. The levels of circulatory, non-protein nitrogen, serum transaminases and thiobarbituric acid reactive substances were significantly increased in ammonium acetate treated rats. These levels were significantly decreased in alpha-ketoglutarate and ammonium acetate treated rats. Similar patterns of alterations were observed in the levels of free fatty acids, triglycerides, phopholipids and cholesterol inbetween various groups. Further non-enzymatic (vitamins C and E) and enzymatic (superoxide dismutase and catalase) antioxidants were significantly decreased in ammonium acetate treated rats; and were significantly increased in alpha-ketoglutarate and ammonium acetate treated rats. The biochemical alterations during alpha-ketoglutarate treatment could be due to (i) the detoxification of excess ammonia, (ii) by participating in the non-enzymatic oxidative decarboxylation in the hydrogen peroxide decomposition process and (iii) by enhancing the proper metabolism of fats which could suppress oxygen radicals generation and thus prevent the lipid peroxidative damages in rats.     

Changes in lipid peroxidation, superoxide dismutase activity, ascorbic acid and phospholipid content in liver of freshwater catfish Heteropneustes fossilis exposed to elevated temperature

1. 1. Lipid peroxidation, superoxide dismutase (SOD) activity, ascorbic acid (AsA) and individual phospholipid contents in liver of fresh water cat fish Heteropneustes fossilis were measured after exposure to different temperatures (25, 27, 32, 37°C) at various times (1–4 h).

2. 2. Lipid peroxidation and superoxide dismutase activity were significantly increased with increases in temperature at various times.

3. 3. Ascorbic acid content was depleted when temperature was increased.

4. 4. After temperature exposure, phosphatidyl inositol was increased while phosphatidyl choline, phosphatidyl serine and phosphatidyl ethanolamine were depleted. Phosphatidic acid level did not change.

5. 5. The findings indicated an increased oxidative stress in liver following increases in temperature at various times. Concurrent with the increase in lipid peroxidation, superoxide dismutase activity and ascorbic acid from the liver of fish varied. It is suggested that depletion of major individual phospholipids following temperature exposure could be due to superoxide created oxidative stress in the liver.

     

Comparison of the effect of alpha-lipoic acid and alpha-tocopherol supplementation on measures of oxidative stress

In vitro studies have shown that alpha-lipoic acid (LA) is an antioxidant. There is a paucity of studies on LA supplementation in humans. Therefore, the aim of this study was to assess the effect of oral supplementation with LA alone and in combination with alpha-tocopherol (AT) on measures of oxidative stress. A total of 31 healthy adults were supplemented for 2 months either with LA (600 mg/d, n = 16), or with AT (400 IU/d, n = 15) alone, and then with the combination of both for 2 additional months. At baseline, after 2 and 4 months of supplementation, urine for F2-isoprostanes, plasma for protein carbonyl measurement and low-density lipoprotein (LDL) oxidative susceptibility was collected. Plasma oxidizability was assessed after incubation with 100 mM 2,2'-azobis (2-amidinopropane) hydrochloride (AAPH) for 4 h at 37 degrees C. LDL was subjected to copper- and AAPH-catalyzed oxidation at 37 degrees C over 5 h and the lag time was computed. LA significantly increased the lag time of LDL lipid peroxide formation for both copper-catalyzed and AAPH-induced LDL oxidalion (p < .05), decreased urinary F2-isoprostanes levels (p < .05), and plasma carbonyl levels after AAPH oxidation (p < .001). AT prolonged LDL lag time of lipid peroxide formation (p < .01 ) and conjugated dienes (p < .01) after copper-catalyzed LDL oxidation, decreased urinary F2-isoprostanes (p < .001), but had no effect on plasma carbonyls. The addition of LA to AT did not produce an additional significant improvement in the measures of oxidative stress. In conclusion, LA supplementation functions as an antioxidant, because it decreases plasma- and LDL-oxidation and urinary isoprostanes.     

Experimental investigation of some systemic effects of nitric oxide inhalation

The goal of this work was to study the influence of nitric oxide inhalation on parameters of blood proand antioxidant systems in rats under both an intact condition and experimental thermal injury. We studied 40 Wistar rats that were divided into four equal groups. The intact group was subjected to no manipulation exñept a single blood sampling, main group I was subjected to inhalation of a air mixture containing 20 ppm of nitric oxide for 10 days, the control group was subjected to thermal injury and conventional treatment, and main group II was subjected to thermal injury and daily inhalation of nitric oxide (20 ppm) for 10 days. We studied the intensity of lipid peroxidation in the blood plasma, the total antioxidant activity, the peroxide resistance of erythrocytes, the level of malondialdehyde in the blood plasma and erythrocytes, and the activity of superoxide dismutase. It was shown that daily inhalations of a mixture containing a low concentration of nitric oxide (20 ppm) modified blood oxidative metabolism in healthy and burned rats. We hypothesized that the activation of lipid peroxidation in erythrocytes accompanied by a pronounced increase in the catalytic activity of superoxide dismutase is a unified response of healthy and burned rats to exogenous nitric oxide exposure. We also observed a moderate prooxidant effect in the blood plasma of healthy animals comparable to that in the erythrocytes of these rats. In the case of thermal injury, oxidative stress tended to be corrected after the end of the course of inhalation.     

Effect of dietary fish on antioxidant parameters of normal and cholesterol stressed rats

Feeding fish (Sardinella longiceps) to normal rats increased lipid peroxidation and total and Se-dependent glutathione peroxidase (GSH-px) activity in erythrocytes and manganese dependent superoxide dismutase (Mn-SOD) activity in liver. Feeding fish to cholesterol stressed rats showed a significant increase in the activity of GSH-px and cholesterol feeding alone, resulted in a significant increase in the lipid peroxidation and liver Mn-SOD activity. The results suggest that the high polyunsaturated fatty acid content of S. longiceps, the fish abundantly available in the west coast of India, does not have any deleterious effect by way of free radical generation. The observed lipid peroxidation is not critical as is evident from the results of glutathione level and other scavenging enzymes.     

Role of Arogh, a polyherbal formulation to mitigate oxidative stress in experimental myocardial infarction

Antioxidant role of Arogh in isoproterenol induced myocardial infarction in rats has been studied. The activity of heart tissue antioxidants like glutathione, superoxide dismutase, catalase, glutathione peroxidase and glutathione-s-transferase were significantly decreased in isoproterenol administered group. The activity of ceruloplasmin and levels of glutathione, vitamins E and C were also found to be substantially decreased in serum with a concomitant rise in lipid peroxide levels after isoproterenol exposure to rats. The synergistic effect of Arogh pretreatment, significantly suppressed the alterations induced by isoproterenol alone in rats.     

Effect of anaesthetic ether on lipid peroxidation and superoxide dismutase isozymes of young and adult rat brain

Changes in lipid peroxidation and superoxide dismutase level in rat brain due to single exposure to diethyl ether (anaesthetic) were studied in 100 and 300 day old rats. Enhancement of superoxide dismutase activity was more pronounced in young rat brain, while the reverse was the case with lipid peroxidation. The neurotoxic effects of diethyl ether may involve active oxygen species and superoxide dismutase activity increases as a defensive adaptation.     

Effect of carnosine alone or combined with α-tocopherol on hepatic steatosis and oxidative stress in fructose-induced insulin-resistant rats

A diet high in fructose (HFr) induces insulin resistance in animals. Free radicals are involved in the pathogenesis of HFr-induced insulin resistance. Carnosine (CAR) is a dipeptide with antioxidant properties. We investigated the effect of CAR alone or in combination with α-tocopherol (CAR?+?TOC) on HFr-induced insulin-resistant rats. Rats fed with HFr containing 60 % fructose received CAR (2 g/L in drinking water) with/without TOC (200 mg/kg, i.m. twice a week) for 8 weeks. Insulin resistance, serum lipids, inflammation markers, hepatic lipids, lipid peroxides, and glutathione (GSH) levels together with glutathione peroxidase (GSH-Px) and superoxide dismutase 1 (CuZnSOD; SOD1) activities and their protein expressions were measured. Hepatic histopathological examinations were performed. HFr was observed to cause insulin resistance, inflammation and hypertriglyceridemia, and increased triglyceride and lipid peroxide levels in the liver. GSH-Px activity and expression decreased, but GSH levels and SOD1 activity and expression did not alter in HFr rats. Hepatic marker enzyme activities in serum increased and marked macro- and microvesicular steatosis were seen in the liver. CAR treatment did not alter insulin resistance and hypertriglyceridemia, but it decreased steatosis and lipid peroxidation without any change in the antioxidant system of the liver. However, CAR?+?TOC treatment decreased insulin resistance, inflammation, hepatic steatosis, and lipid peroxidation and increased GSH-Px activity and expression in the liver. Our results may indicate that CAR?+?TOC treatment is more effective to decrease HFr-induced insulin resistance, inflammation, hepatic steatosis, and dysfunction and pro-oxidant status in rats than CAR alone.     

Evalution of toxicity of abcisic acid and gibberellic acid in rats: 50 days drinking water study

In the present study, the influence of subchronic effects of two plant growth regulators (PGRs) [Abcisic acid (ABA) and Gibberellic acid (GA3)] on antioxidant defense systems [reduced glutathione (GSH), glutathione reductase (GR), superoxide dismutase (SOD), glutathione-S-transferase (GST) and catalase (CAT)] and lipid peroxidation level (malondialdehyde = MDA) in various tissues of the rat were investigated during treatment as a drinking water model. 75 ppm of ABA and GA3 in drinking water were continuously administered orally to rats (Sprague-Dawley albino) ad libitum for 50 days. The PGRs treatments caused different effects on the antioxidant defense systems and MDA content of dosed rats compared to controls. The lipid peroxidation end product MDA significantly increased in the lungs, heart and kidney of rats treated with GA3 without significant change in the spleen. ABA caused also a significant increase in MDA content in the spleen, lungs, heart and kidney. The GSH levels were significantly depleted in the spleen, lungs and stomach of rats treated with ABA without any change in the tissues of rats treated with GA3 except the kidney where it increased. Antioxidant enzyme activities such as SOD significantly increased in the lungs and stomach and decreased in the spleen and heart tissues of rats treated with GA3. Meanwhile, SOD significantly decreased in the spleen, heart and kidney and increased in the lungs of rats treated with ABA. While CAT activity significantly decreased in the lungs of rats treated with GA3, a significant increase occurred in the heart of rats treated with both PGRs. On the other hand, the ancillary enzyme GR activity in the tissues were either significantly depleted or not changed with PGRs treatment. The drug metabolizing enzyme GST activity significantly decreased in the lungs of rats treated with ABA but increased in the stomach of rats treated with both PGRs. As a conclusion, the rats resisted oxidative stress via the antioxidant mechanism. But the antioxidant mechanism could not prevent the increases in lipid peroxidation in rat's tissues. This data, along with changes, suggests that PGRs produced substantial systemic organ toxicity in the spleen, lungs, stomach, heart and kidney during a 50-day period of subchronic exposure.