Adverse Cardiac Responses to Alpha-Lipoic Acid in a Rat Diabetic Model: Possible Mechanisms?

Alpha lipoic acid (LA) is widely used as an antioxidant for the treatment of diabetes and its complications; however, the pro-oxidant potential of LA has been recently reported. This study was designed to investigate whether LA supplementation could have pro-oxidant effects on cardiac tissues in normal and diabetic rats. Diabetes was induced by single dose of streptozotocin (55 mg/kg/i.p.). Diabetic and normal rats were treated with LA (100 mg/kg/day) for 45 days. LA supplementation resulted in oxidative protein damage as evident by significant reduction in the cardiac levels of protein thiol in LA-treated normal rats compared with normal controls (P<0.01) together with a significant elevation (P<0.001) in the plasma levels of advanced oxidation protein products (AOPP) in LA-treated normal rats and in LA-treated diabetic group compared with the normal controls. Data showed that LA supplementation failed to prevent cardiac complications in diabetic rats, and led to cardiac toxicity in normal rats as indicated by pathological changes (cellular infiltration, fibrosis, and degeneration) and by the elevation of serum cardiac biomarkers compared with normal controls. Pro-oxidant effects of a relatively high dose of LA suggest that careful selection of appropriate doses of LA in reactive oxygen species - related diseases are critical.