Alpha-lipoic acid preserves the structural and functional integrity of red blood cells by adjusting the redox disturbance and decreasing O-GlcNAc modifications of antioxidant enzymes and heat shock proteins in diabetic rats

Abstract

The aim of this study was to investigate whether the daily administration of alpha-lipoic acid (LA) during 4 weeks prevents the redox disturbance in red blood cells (RBC) described in diabetes Multiple low-dose streptozotocin (STZ) diabetes was induced in rats by the administration of 40 mg/kg STZ intraperitoneally (i.p.) for 5 consecutive days. LA was applied at a dose of 10 mg/kg i.p. for 4 weeks, starting from the last day of STZ administration. The LA-treated diabetic rats exhibited a general systemic improvement, revealed as the near restoration of body weight and of essential biochemical parameters. The latter was displayed as decreased hyperglycemia, lower triglyceride levels and lower serum activities of alanine aminotransferases and aspartate aminotransferases that point to a general improvement of diabetes-linked organ "lesions". The LA-treated diabetic rats also exhibited significant alleviation of oxidative stress, manifested as decreased lipid peroxidation and lower glycation levels of serum proteins and hemoglobin, while the RBC exhibited increased activities of antioxidant enzymes and elevated levels of reduced glutathione. In RBC, this was accompanied by decreased post-translational glycosylation by O-bound beta-N-acetylglucosamine (O-GlcNAc) of the antioxidant enzymes superoxide dismutase and catalase and of heat shock proteins HSP70 and HSP90. LA through its powerful antioxidant activity preserves the structural and functional integrity of RBC in diabetes. The RBC can then assume a more efficient role as the first line of systemic defense against diabetic complications arising from oxidative stress-induced damage of other tissues and organs.