α-Tocopherol Reduces Proteinuria, Oxidative Stress, and Expression of Transforming Growth Factor β1 in IgA Nephropathy in the Rat

Abstract

Oxidative stress and the fibrogenic cytokine transforming growth factor β1 (TGFβ1) have been implicated in the pathogenesis and progression of IgA nephropathy. In the present study, we used α-tocopherol as a dietary supplement to test the hypothesis that the proteinuria, oxidative stress, and TGFβ mRNA can be more effectively lowered with higher doses of α-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 TGFβ1 mRNA, as well as the severity of proteinuria, was blunted by α-tocopherol. Our data suggested that conventional dosage of α-tocopherol at 100 IU/kg chow lowered kidney TGFβ1 to control values and increasing the dose by 212-fold or even 5-fold resulted in no further reduction in TGFβ1 mRNA. Significant reduction of proteinuria was achieved better with a dose of 250 IU/kg chow of α-tocopherol supplementation than with the 100 IU/kg chow. We conclude that α-tocopherol at this dose is efficacious in controlling proteinuria, downregulating TGFβ1, and reducing oxidative stress in experimental IgA nephropathy. Doubling this dose achieved no further benefits.