Influence of alpha-tocopherol over the time course of experimental IgA nephropathy

The present study investigated the pathogenesis and the time course of kidn ey injury in experimental IgA nephropathy. In order to determine an appropr iate period in the course of experimental IgA nephropathy to study renal in jury and repair, we examined proteinuria and IgA deposition in the renal me sangium after 4, 8, and 16 weeks of mucosal challenge by bovine gamma globu lins (BGG) provided in the drinking water. The hallmark of IgA deposition i n the mesangium was present after 4 weeks and 8 weeks of EGG inoculation, b ut by 16 weeks, the mesangial IgA deposition had resolved. In addition, we confirmed our previous report on the beneficial effects of alpha-tocopherol in reducing proteinuria in IgA nephropathy at 8 weeks, and extended this o bservation to investigate the effects of dietary supplementation of alpha-t ocopherol at both 4 weeks and 16 weeks. Proteinuria resolved spontaneously at 16 weeks. There is oxidative stress, as suggested by the elevation in pl asma and renal malondialdehyde content, and increased Fibrogenic cytokine m essage, as suggested by elevated transforming growth factor beta 1 mRNA. Th ese increases were clearly blunted by alpha-tocopherol at both 4 weeks and 8 weeks. Treatment with alpha-tocopherol was associated with a significant reduction in the severity of proteinuria. Thus, our data suggest that the p eriod between 4 and 8 weeks of BGG vaccination could be relevant in designi ng an appropriate model to study the molecular biology of the pathogenesis of renal injury and the effects of treatment. The 16-week model may be usef ul in exploring gene expression involved with spontaneous resolution.