Alpha-lipoic acid treatment ameliorates metabolic parameters, blood pressure, vascular reactivity and morphology of vessels already damaged by streptozotocin-diabetes.
The present study investigated the effects of alpha-lipoic acid treatment (50 mg/kg/day) on the metabolism and vascular condition already damaged by streptozotocin (STZ)-diabetes in rats. Carbohydrate and lipid metabolism, oxidative stress and antioxidant status were assessed in non-diabetic controls, 12-week untreated diabetic and 12-week treated diabetic (untreated for 6 weeks and then treated with alpha-lipoic acid for the last 6 weeks) rats. Blood pressures of rats were measured by tail-cuff method. Vascular reactivity was evaluated in isolated aortic rings. Morphology of aorta was examined by electron microscopy technique. Alpha-lipoic acid treatment effectively reversed body weight, blood glucose, plasma insulin, cholesterol, triglycerides and lipid peroxidation levels of diabetic animals. STZ-diabetes resulted in increased blood pressure, which was partially improved by alpha-lipoic acid treatment. Although the superoxide dismutase (SOD) activity in aortic homogenates was not changed by diabetes or antioxidant treatment, catalase or glutathione peroxidase (GPx) activity significantly increased in untreated diabetic rats. Alpha-lipoic acid treatment improved catalase activity in diabetic aorta. The contractile effect of phenylephrine markedly increased in diabetic rings, which was completely reversed by alpha-lipoic acid treatment. The maximum vasorelaxant response of pre-contracted aortic rings exposed to cumulatively increased concentrations of acetylcholine was unaffected by diabetes or antioxidant treatment. Sodium nitroprusside-induced endothelium-independent relaxations were similar in all experimental groups. Various alterations caused by STZ-diabetes in aorta structure were partially ameliorated by alpha-lipoic acid treatment. The potency of alpha-lipoic acid on the reversal of hypertension by affecting vascular reactivity and morphology as well as general metabolism of diabetic rats confirms the importance of hyperglycemia-induced oxidative stress in the development of diabetes-induced vascular complications and suggests a potential therapeutic approach.
Department of Pharmacology, Faculty of Pharmacy, Ankara University, Tandogan, Turkey.
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G
Koçak
F
F
Aktan
O
O
Canbolat
C
C
Ozoğul
S
S
Elbeğ
N
N
Yildizoglu-Ari
C
C
Karasu
D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology*; D001011:Aorta / Q000187:drug effects* / Q000473:pathology; D001794:Blood Pressure / Q000187:drug effects*; D050260:Carbohydrate Metabolism; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D004195:Disease Models, Animal; D050356:Lipid Metabolism; D015227:Lipid Peroxidation; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar; D013311:Streptozocin; D008063:Thioctic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D013997:Time Factors
D000975:Antioxidants; D013311:Streptozocin; D008063:Thioctic Acid