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》

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》

Changes in lipid metabolism and antioxidant defense status in spontaneously hypertensive rats and Wistar rats fed a diet enriched with fructose and saturated fatty acids.

Larger doses of fructose and saturated fat have been associated with oxidative stress and development of hypertension. The effects of modest amounts of fructose and saturated fatty acids on oxidative stress are unknown. To increase knowledge on this question, 10-wk-old spontaneously hypertensive rats and Wistar rats were fed for 8 wk with a control diet or an experimental diet enriched with fructose (18%) and saturated fatty acids (11%; FS diet). The total antioxidant status of organs and red blood cells was assayed by monitoring the rate of free radical-induced red blood cell hemolysis. Sensitivity of very low-density lipoprotein and low-density lipoprotein (VLDL-LDL) to copper-induced lipid peroxidation was determined as the production of thiobarbituric acid-reactive substances. Antioxidant enzymes and vitamins were also measured to establish the oxidative stress effect. The FS diet did not affect blood pressure in either strain, but it increased plasma insulin concentrations only in Wistar rats without affecting those of glucose of either strain. The FS diet significantly enhanced plasma and VLDL-LDL triacylglycerol concentrations without affecting concentrations of VLDL-LDL thiobarbituric acid-reactive substances. The decreased content of arachidonic acid and total polyunsaturated fatty acids in VLDL-LDL by the FS diet may have prevented lipid peroxidation in this fraction. Moreover, FS consumption by both strains was accompanied by a significant increase in total antioxidant capacity of adipose tissue, muscle, heart, and liver. This may have resulted from increased tissue ascorbic acid levels and glutathione peroxidase and glutathione reductase activities in tissues. These findings clearly indicate that the FS diet did not alter blood pressure of spontaneously hypertensive rats and Wistar rats. The FS diet resulted in hypertriglyceridemia but increased the total antioxidant status, which may prevent lipid peroxidation in these rats.

Girard A ，Madani S ，El Boustani ES ，Belleville J ，Prost J ... -  《NUTRITION》

Metformin attenuates blood lipid peroxidation and potentiates antioxidant defense in high fructose-fed rats.

The implication of oxidative stress in the pathology of insulin resistance has been shown recently. We investigated the effect of an insulin sensitizer, metformin, on the plasma lipid peroxidation and antioxidant defense system in the erythrocytes of high fructose fed rats which form an animal model of insulin resistance. The experimental animals were divided into two batches of 12 animals each. The control batch received the control diet, containing starch; the fructose group was given the high fructose diet. At the end of second week these were subdivided into two groups; one was given metformin (50 mg/kg/day in water) by gastric intubation and other group was left untreated. The rats were continued on the same dietary regimen for the next two weeks. Fructose-fed rats showed hyperglycemia, hyperinsulinemia and hypertriglyceridemia at the end of four weeks. Enhanced plasma lipid peroxidation and inadequate cellular antioxidant defense system were observed in them. Administration of metformin was associated with significant normalization of circulating insulin, glucose and triglyceride concentrations. The abnormal triglyceride distribution in the lipoprotein fractions was also ameliorated by metformin therapy. The imbalance between peroxidation and antioxidant defense system was mitigated when fructose-fed rats were treated with metformin. In the control rats, metformin did not affect the parameters studied. Significant positive correlation was obtained between insulin, triglycerides and glucose concentrations with lipid hydroperoxides suggesting that these metabolic variables could influence the lipid peroxide levels in plasma.

Srividhya S ，Ravichandran MK ，Anuradha CV 《-》

Taurine modulates antioxidant potential and controls lipid peroxidation in the aorta of high fructose-fed rats.

High dosage of fructose induces insulin resistance, glucose intolerance and alterations in plasma lipid profile in normal rats. Recently, it has been shown that these rats also develop oxidative stress, which plays a prominent role in diabetic pathology. We now report the effect of taurine on the susceptibility of the aorta to lipid peroxidation and also on the activities of enzymic and non-enzymic antioxidants in rats fed a high fructose-diet for 4 weeks. Fructose-fed rats were more susceptible to lipid peroxidation as measured by thiobarbituric acid reactivity, and antioxidant status was significantly lower. Taurine supplementation caused a significant reduction in the production of thiobarbituric acid--reactive substances and significant rises in antioxidant enzyme activities. The levels of lipid peroxides, diene conjugates, lipofuscin and hydroperoxides were significantly higher in fructose-fed rats. When these rats received taurine in drinking water, no peroxidative changes were observed. Increased aorta lipid peroxidation could play a role in the pathology associated with fructose-feeding, and taurine reduces the lipid peroxidation by inducing antioxidant enzymes.

Anitha Nandhini AT ，Balakrishnan SD ，Anuradha CV 《-》