Alpha-lipoic acid attenuates hyperglycemia and prevents glomerular mesangial matrix expansion in diabetes.

Previous studies demonstrated that 2 mo of dietary supplementation with alpha-lipoic acid (LA) prevented early glomerular injury in non-insulin-treated streptozotocin diabetic rats (D). The present study examined the effects of chronic LA supplementation (30 mg/kg body wt per d) on nephropathy in D after 7 mo of diabetes. Compared with control rats, D developed increased urinary excretion of albumin and transforming growth factor beta, renal insufficiency, glomerular mesangial matrix expansion, and glomerulosclerosis in association with depletion of glutathione and accumulation of malondialdehyde in renal cortex.

Overexpression of manganese superoxide dismutase suppresses increases in collagen accumulation induced by culture of mesangial cells in high-media glucose.

Superoxide has been implicated in the cellular signalling pathways, which regulate growth of mesangial cells (MC) and vascular smooth muscle cells. Manganese (Mn)(2+)-dependent superoxide dismutase (SOD-2) is primarily responsible for metabolism of superoxide produced in mitochondria by respiratory chain activity during aerobic metabolism of glucose and other substrates. In the current studies, we examined the role of superoxide in the stimulation of collagen accumulation induced in MC by culture in media containing a high concentration of glucose.