Vitamin E inhibits renal mRNA expression of COX II, HO I, TGF beta, and osteopontin in the rat model of cyclosporine nephrotoxicity

Background. In a rat model of cyclosporine (CsA) nephrotoxicity, vitamin E preserves renal function and reduces free radicals, vasoconstrictive thromb oxanes, and tubulointerstitial fibrosis, We examined the effect of vitamin E on tubule gene expression in this model, Methods. In two of three groups, rats were treated with either CsA, or CsA plus vitamin E, whereas the control group received vehicles. We pooled puri fied tubules or whole kidney tissue in a novel manner to represent each tre atment group, harvested RNA, and performed rigorously controlled qualitativ e reverse transcription-polymerase chain reaction. Results, Cyclooxygenase (COX) I mRNA was detectable in control animals, was increased by CsA, but was unchanged by vitamin E, COX II mRNA was detected in controls, was inhibited in the CsA group, and was further inhibited wit h vitamin E, Hemeoxygenase I and TGF-beta and osteopontin mRNA were increas ed in the CsA-treated group and were inhibited by vitamin Conclusions. Our data support the involvement of free radicals, COX pathway s, and pro-fibrotic genes in cyclosporine nephrotoxicity and suggest that t he salutary effect of vitamin E involves the suppression of some of these g enes.