Lipoic acid restores antioxidant system in tissues of hyperinsulinaemic rats.

Feeding rats with high fructose induces insulin resistance, hyperinsulinaemia, elevation of blood glucose level and impaired glucose tolerance. Oxidative stress plays a vital role in pathology associated with insulin resistance. The present study was to investigate the effects of alpha-lipoic acid (LA) on the oxidant-antioxidant balance in liver and kidney of high fructose-fed rats. Male Wistar rats (170-180 g) were divided into six groups. The control group received diet containing starch; the fructose group was given a high fructose diet (>60% of total calories); the third and fourth groups were given fructose diet and administered with two different doses of lipoic acid as low dose (35 mg/kg body weight) and high dose (70 mg/kg bw) intraperitoneally using olive oil as vehicle; the fifth group received control diet and was administered with lipoic acid (70 mg/kg bw); the sixth group received the control diet and olive oil. The rats were maintained in their respective dietary regimen for 20 days. Lipid peroxidation indices and antioxidant status in liver and kidney were quantitated. The rats fed fructose showed increased levels of lipid hydroperoxides, thiobarbituric acid reactive substances (TBARS), conjugated dienes, and impaired antioxidant defence potential as evidenced by a decrease in the levels of non-enzymatic and enzymatic antioxidants. Treatment with LA to the fructose-fed rats mitigated these alterations and LA was effective uniformly at both the closes. Increased lipid peroxidation and inadequate antioxidant system are observed in the high dose fructose-fed rats. LA administration restored the antioxidant potential and lowered lipid peroxidation. These findings strengthen the utility of LA in the management of insulin resistance and associated pathology.

Thirunavukkarasu V ，Anitha Nandhini AT ，Anuradha CV 《INDIAN JOURNAL OF MEDICAL RESEARCH》

Influence of alpha-lipoic acid on lipid peroxidation and antioxidant defence system in blood of insulin-resistant rats.

High fructose feeding induces insulin resistance and hyperinsulinaemia in rats. A role for oxidative stress in the occurrence of insulin resistance has been suggested by several workers. The aim of this study was to investigate the effect of alpha-lipoic acid (LA) on oxidant-antioxidant balance in rats fed on a high-fructose diet that showed characteristic features of insulin resistance. Male Wistar rats weighing 150-170 g were divided into seven groups. The control group received the control diet containing starch. The fructose group was given a high-fructose diet (>60% of total calories). The third and fourth groups were given fructose diet and were administered two different doses of LA at a low dose (35 mg/kg body weight) and high dose (70 mg/kg body weight) using olive oil as vehicle. The fifth group received fructose diet and olive oil. The sixth group received control diet and was administered LA (70 mg/kg body weight). And, the seventh group received the control diet and olive oil. Products of lipid peroxidation and activities of enzymic antioxidants, namely superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase and glutathione reductase, in red blood cells were assayed. Levels of non-enzymic antioxidants alpha-tocopherol, ascorbic acid and reduced glutathione were determined in plasma. The levels of lipid peroxides, diene conjugates and thiobarbituric acid-reactive substances were significantly higher in fructose-fed rats. Inadequate antioxidant system was observed in high-fructose-fed rats. Treatment of fructose rats mitigated the imbalance between peroxidation and antioxidant defence system at both the doses tested. Increases in glucose, triglycerides, free fatty acids, insulin and insulin resistance were observed in fructose-fed rats. LA administration prevented these alterations and improved insulin sensitivity. Significant positive correlations were obtained between insulin resistance and lipid peroxidation indices. Increased lipid peroxidation and deficient antioxidant system are observed in high-fructose-fed rats. LA administration preserves the antioxidant system and lowers lipid peroxidation. The findings suggest an interrelationship between lipid peroxidation and insulin resistance.

Thirunavukkarasu V ，Anuradha CV 《DIABETES OBESITY & METABOLISM》

Effect of taurine on biomarkers of oxidative stress in tissues of fructose-fed insulin-resistant rats.

Nandhini AT ，Thirunavukkarasu V ，Ravichandran MK ，Anuradha CV ... -  《SINGAPORE MEDICAL JOURNAL》

High dietary salt decreases antioxidant defenses in the liver of fructose-fed insulin-resistant rats.

In this study we investigated the hypothesis that a high-salt diet to hyperinsulinemic rats might impair antioxidant defense owing to its involvement in the activation of sodium reabsorption to lead to higher oxidative stress. Rats were fed a standard (CON), a high-salt (HS), or a high-fructose (HF) diet for 10 weeks after which, 50% of the animals belonging to the HF group were switched to a regimen of high-fructose and high-salt diet (HFS) for 10 more weeks, while the other groups were fed with their respective diets. Animals were then euthanized and their blood and liver were examined. Fasting plasma glucose was found to be significantly higher (approximately 50%) in fructose-fed rats than in the control and HS rats, whereas fat liver also differed in these animals, producing steatosis. Feeding fructose-fed rats with the high-salt diet triggered hyperinsulinemia and lowered insulin sensitivity, which led to increased levels of serum sodium compared to the HS group. This resulted in membrane perturbation, which in the presence of steatosis potentially enhanced hepatic lipid peroxidation, thereby decreasing the level of antioxidant defenses, as shown by GSH/GSSG ratio (HFS rats, 7.098±2.1 versus CON rats, 13.2±6.1) and superoxide dismutase (HFS rats, 2.1±0.05 versus CON rats, 2.3±0.1%), and catalase (HFS rats, 526.6±88.6 versus CON rats, 745.8±228.7 U/mg ptn) activities. Our results indicate that consumption of a salt-rich diet by insulin-resistant rats may lead to regulation of sodium reabsorption, worsening hepatic lipid peroxidation associated with impaired antioxidant defenses.

Dornas WC ，de Lima WG ，dos Santos RC ，Guerra JF ，de Souza MO ，Silva M ，Souza e Silva L ，Diniz MF ，Silva ME ... -  《-》

Cardiac lipids and antioxidant status in high fructose rats and the effect of alpha-lipoic acid.

Thirunavukkarasu V ，Anitha Nandhini AT ，Anuradha CV 《NUTRITION METABOLISM AND CARDIOVASCULAR DISEASES》