α-tocopherol reduces proteinuria, oxidative stress, and expression of transforming growth factor β1 in IgA nephropathy in the rat

Oxidative stress and the fibrogenic cytokine transforming growth factor beta 1 (TGF beta 1) have been implicated in the pathogenesis and progression of IgA nephropathy. In the present study, we used alpha-tocopherol as a dietary supplement to test the hypothesis that the proteinuria, oxidative stress, and TGF beta mRNA can be more effectively lowered with higher doses of alpha-tocopherol. Hematuria, proteinuria, and mesangial IgA deposition are parameters which characterize IgA nephropathy. IgA nephropathy was induced by bovine gamma globulin oral immunization in rats during an 8-week course, and all hallmarks of IgA nephropathy were produced in this 8-week animal model. The elevation in renal malondialdehyde content and TGF beta 1 mRNA, as well as the severity of proteinuria, was blunted by alpha-tocopherol, Our data suggested that conventional dosage of alpha-tocopherol at 100 IU/kg chow lowered kidney TGF beta 1 to control values and increasing the dose by 21/2-fold or even 5-fold resulted in no further reduction in TGF beta 1 mRNA. Significant reduction of proteinuria was achieved better with a dose of 250 IU/kg chow of alpha-tocopherol supplementation than with the 100 IU/kg chow. We conclude that alpha-tocopherol at this dose is efficacious in controlling proteinuria, downregulating TGF beta 1, and reducing oxidative stress in experimental IgA nephropathy. Doubling this dose achieved no further benefits. (C) 1998 Academic Press.