Investigation of the effects of alpha-lipoic acid on oxidant-antioxidant systems in plasma and some tissues of chronic hyperhomocysteinemia induced rats

INVESTIGATION OF THE EFFECTS OF ALPHA-LIPOIC ACID ONOXIDANT-ANTIOXIDANT SYSTEMS IN PLASMA AND SOME TISSUESOF CHRONIC HYPERHOMOCYSTEINEMIA INDUCED RATSFunda GÜLCÜ BULMUŞABSTRACTThe increase in plasma homocysteine levels is an important risk factor forvascular and cardiovascular diseases through free radical production and severalother mechanisms. On the contrary, α-lipoic acid is a strong, therapeuticantioxidant with treatment potential in many diseases especially related withoxidative stress. In the present study, the effects of homocysteine in oxidant-antioxidant systems in chronic hyperhomocysteinemia induced rats and how α-lipoic acid would change these effects were aimed to be investigated.A total of 45 male Wistar albino rats weighing 200-250 gr. were used in thestudy and rats were divided into 3 groups. Group 1 (n=15, control group; 1 ml/kgnormal saline administered i.p. for 6 weeks); Group 2 (n=15, hHcy group; 1 ml/kgnormal saline administered i.p. and chronic hyperhomocysteinemia was inducedby adding 1 g/kg/day L-methionine in tap water for 6 weeks); Group 3 (n=15,hHcy+LA group; chronic hyperhomocysteinemia induced by adding 1 g/kg/dayL-methionine in tap water and 100 mg/kg/day α-lipoic acid administered i.p. for 6weeks). After 6 weeks, rats were decapitated; blood samples, liver, kidney, heartand brain tissue samples obtained for biocehemical parameters and aorta samplesfor histopathological investigation.Lipoic acid administration was shown to decrease plasma Hcy levelssignificantly and prevent hHcy development in experimentallyhyperhomocysteinemia induced rats. Plasma and tissue MDA levels, as anindicator of lipid peroxidation, were found significantly higher in Group 2 thanGroup 1; whereas lipoic acid treatment was seen to lower MDA levelssignificantly. Hyperhomocysteinemia led to a significant decrease in GSH-Px andCAT activities in erythrocyte, liver and kidney tissues but not in heart and brain.On the other hand, there was no significant effect of hyperhomocysteinemia onerythrocyte and tissue SOD activities. Lipoic acid was shown to increaseerythrocyte and tissue SOD, CAT and GSH-Px activities and erythrocyte GSHlevels significantly, except erythrocyte SOD activity. Hyperhomocysteinemia wasalso shown to increase the levels of lipid parameters (cholesterol, LDL, VLDL,triglyceride) and lipoic acid was found to prevent this adverse effect of hHcy. Inaddition, it was found that hHcy lead to degenerative vascular damage in aortaand lipoic acid was shown to prevent these vascular changes.In conclusion; lipoic acid was found to decrease lipid peroxidation, increaseantioxidant activity and improve lipid profile as well as preventhyperhomocysteinemia and related vessel lesions, thus have vasoprotectiveeffects. When all these beneficial effects of lipoic acid taken into account, it couldbe thought to have a strong potential for being used as supplementation incardiovascular diseases.Key Words: Hyperhomocysteinemia, α-lipoic acid, L-methionine, oxidant-antioxidant systems.