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. LA prevented or ameliorated all of these changes in D. Because chronic LA supplementation also attenuated hyperglycemia in D after 3 mo, its effects on renal injury were compared with treatment of rats with sufficient insulin to maintain a level of glycemic control for the entire 7-mo period (D-INS) equivalent to that observed with LA during the final 4 mo. Despite superior longitudinal glycemic control in D-INS, urinary excretion of albumin and transforming growth factor beta, glomerular mesangial matrix expansion, the extent of glomerulosclerosis, and renal cortical malondialdehyde content were all significantly greater, whereas cortical glutathione content was lower than corresponding values in D given LA. Thus, the renoprotective effects of LA in D were not attributable to improved glycemic control alone but also likely reflected its antioxidant activity. The combined antioxidant and hypoglycemic actions of LA both may contribute to its utility in preventing renal injury and other complications of diabetes.
Melhem
Mona F
MF
Departments of *Pathology and Medicine, VA Pittsburgh Healthcare System and University of Pittsburgh, Pittsburgh, Pennsylvania.
Craven
Patricia A
PA
Departments of *Pathology and Medicine, VA Pittsburgh Healthcare System and University of Pittsburgh, Pittsburgh, Pennsylvania.
Liachenko
Julia
J
Departments of *Pathology and Medicine, VA Pittsburgh Healthcare System and University of Pittsburgh, Pittsburgh, Pennsylvania.
DeRubertis
Frederick R
FR
Departments of *Pathology and Medicine, VA Pittsburgh Healthcare System and University of Pittsburgh, Pittsburgh, Pennsylvania.
D000419:Albuminuria / Q000209:etiology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001786:Blood Glucose / Q000032:analysis; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000150:complications / Q000473:pathology / Q000503:physiopathology*; D003928:Diabetic Nephropathies / Q000517:prevention & control*; D005260:Female; D005920:Glomerular Mesangium / Q000187:drug effects* / Q000473:pathology*; D005978:Glutathione / Q000378:metabolism; D006943:Hyperglycemia / Q000097:blood*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007672:Kidney Cortex / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D051381:Rats; D051437:Renal Insufficiency / Q000209:etiology / Q000517:prevention & control; D008063:Thioctic Acid / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000652:urine
D000975:Antioxidants; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D016212:Transforming Growth Factor beta; D008315:Malondialdehyde; D008063:Thioctic Acid; D005978:Glutathione