RESVERATROL PROTECT AGAINST HOMOCYSTEINE-INDUCED RENAL DAMAGE THROUGH ANTIOXIDANT ACTION IN SPONTANEOUS HYPERTENSIVE RATS

Abstract

Objective: The aim of this study was to investigate the effect of resveratrol in renal damage and the underlying mechanism induced by Hhcy in SHRs. Design and method: Twenty-four SHRs were divided into control group, Hhcy group, Hhcy + resveratrol (Hhcy+Res) group. Hhcy groups were given intraperitoneal injection of homocysteine. In addition, the Hhcy + Res group was given resveratrol by gavage. The Systolic blood pressure (SBP), diastolic blood pressure (DBP), plasma Hcy, serum malondialdehyde (MDA), superoxide dismutase (SOD) and the urinary microalbumin (UACR) were measured. To quantify RNA and protein expression levels, the mRNA and the protein expression of nephrin and NADPH oxidase subunits NOX2 and NOX4 in the kidney were examined by quantitative Real-time PCR and western blot. Renal histological or pathological changes were observed under light and electron microscope. Results: There was no difference in blood pressure before and after Hcy or Res intervention among groups. The homocysteine levels in Hhcy and Res group were significantly higher than that in control group, which showed that the model was successfully built by intraperitoneal injection. The serum SOD level was significantly decreased in Hhcy group, while it was increased in Res group. On the contrary, the serum MDA and UACR levels of model group were significantly increased. after the intervention of resveratrol, the MDA and UACR levels were reduced. Furthermore, the expression levels of mRNA and the protein of NOX2 and NOX4 were elevated while those of the nephrin were reduced in Hhcy group. Resveratrol significantly reduced the expressions of NOX2 and NOX4, and increased the expression of nephrin in renal tissue of SHRs with Hhcy. Conclusions: These results suggested that resveratrol may improve renal damage in hypertensive rats with Hhcy by exerting oxidative stress beyond blood pressure.