We tested the hypothesis that oral administration of red wine polyphenols, provinol (PV), prevents the development of nephrotoxicity induced by chronic treatment of rats with the immunosuppressive agent, cyclosporine (CsA). CsA treatment produced a significant increase of systolic blood pressure, did not affect urinary output but caused a significant decrease in creatinine clearance. Also, CsA induced histological alterations including fibrosis in the brain regions. These effects of CsA were associated with an increase in reactive oxygen species, inducible nitric oxide synthase (iNOS) and nuclear transcription factor, NF-κB (Fig.). Provinol alone did not affect any of the parameters measured as compared to controls. However, provinol prevented the increase of systolic pressure as well as fibrosis induced by CsA treatment. The protective mechanism involved reduction of both oxidative stress and increased inducible NO synthase expression via the NF-κB pathway (Fig.). These results suggest that oral administration of provinol is protective against CsA-induced increase in blood pressure and nephrotoxicity. Reduced oxidative stress in association with its anti-inflammatory property at the level of NF-κB and inducible nitric oxide synthase account for the effect of provinol. These data provide a pharmacological basis for the beneficial effects of plant-derived polyphenols against renal diseases associated with immunosuppressive agents.
(Interinstitute project: Pecháňová, Kojšová, zahraničný partner: Rezzani, Bianchi, Buffoli).
Buffoli, B. - Pecháňová, O. - Kojšová, S. - Andriantsitohaina, R. - Giugno, L. - Bianchi, R. - Rezzani, R. Provinol Prevents CsA-induced Nephrotoxicity by Reducing Reactive Oxygen Species, iNOS and NF-kB Expression. In Journal of Histochemistry and Cytochemistry. Vol. 35, no. 6 (2005), p. 362-368. (2,513 – IF2005)
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