Effects of Dietary Supplementation of a alpfa Lipoic Acid on Early Glomerular Injury in Diabetes Mellitus

Antioxidants, in particular vitamin E (VE), have been reported to protect against diabetic renal injury. a-Lipoic acid (LA) has been found to attenuate diabetic peripheral neuropathy, but its effects on nephropathy have not been examined. In the present study, parameters of glomerular injury were examined in streptozotocin diabetic rats after 2 mo on unsupple- mented diets and in diabetic rats that received the lowest daily dose of dietary LA (30 mg/kg body wt), VE (100 IU/kg body wt), or vitamin C (VC; 1 g/kg body wt), which detectably increased the renal cortical content of each antioxidant. Blood glucose values did not differ among the diabetic groups. At 2  mo, inulin clearance, urinary albumin excretion, fractional albumin clearance, glomerular volume, and glomerular content of immunoreactive transforming growth factor-b (TGF-b) and collagen a1 (IV) all were significantly increased in unsupplemented D compared with age-matched nondiabetic controls. With the exception of inulin clearance, LA prevented or sig-nificantly attenuated the increase in all of these glomerular parameters in D, as well as the increases in renal tubular cellTGF-bseen in D. At the dose used, VE reduced inulin clear-ance in D to control levels but failed to alter any of the otherindices of glomerular injury or to suppress renal tubular cell TGF-b in D. VC suppressed urinary albumin excretion, fractional albumin clearance, and glomerular volume but not glo- merular or tubular TGF-b or glomerular collagen a 1 (IV) content. LA but not VE or VC significantly increased renal cortical glutathione content in D. These data indicate that LA is effective in the prevention of early diabetic glomerular injury and suggest that this agent may have advantages over high doses of either VE or VC.

 

Reference
MONA F. MELHEM,* PATRICIA A. CRAVEN,† and FREDERICK R. DERUBERTIS

† Departments of *Medicine and †Pathology, Veterans Affairs Medical Center and University of Pittsburgh, Pittsburgh, Pennsylvania.