Modulation of the transforming growth factor beta1 by vitamin E in early nephropathy

The aim of this study was to investigate the pharmacological activity of an antioxidant, alpha-tocopherol (vitamin E, VE) in streptozotocin-induced diabetic rats and study its role in modulating the transforming growth factor beta1 (TGF-beta1).

Male Sprague-Dawley rats were treated with streptozotocin to induce diabetes. VE and/or insulin (INS) were administered daily during treatment periods of 3, 5, 7 and 10 days. Plasma glucose and fructosamine were measured in diabetic rats at the end of each treatment period. Samples of plasma, urine and renal cortex were analyzed for changes in protein and lysozyme excretion, reduced glutathione and malondialdehyde formation. TGF-beta1 was determined by ELISA and expression of TGF-beta1 mRNA was investigated by RT-PCR and Northern blot analysis.

Diabetes-induced glycemic stress was suppressed by INS, VE or a combination of INS and VE. Diabetes-induced increases of glucose, protein and lysozyme excretion were markedly depressed after 10-day treatment with INS, VE and the combination of INS and VE. Decreased glutathione content in the renal cortex of diabetic rats recovered towards control values, especially after 10-day treatment. Malondialdehyde content increased in diabetic rats and was reduced towards control value following 7- and 10-day treatments. Treatment of diabetic rats with INS, VE or the combination of INS and VE decreased elevated TGF-beta1 in plasma, decreased excretion of TGF-beta1 in urine, and decreased renal cortex TGF-beta1 mRNA levels.

Diabetes-induced overexpression of TGF-beta1 mRNA was suppressed by VE and INS after 5-, 7- and 10-day treatments. The results obtained with the antioxidant VE suggest that oxidative stress is involved in the development of diabetic nephropathy. Therefore, VE treatment may be effective in early stages of diabetic nephropathy to decrease or prevent pathological complications.