Resveratrol: A new approach to ameliorate hyperhomocysteinaemia-induced renal dysfunction

Hypertension is a common cause of kidney injury and renal damage occurs earlier and is more serious in patients with hypertension and hyperhomocysteinaemia (HHCY). Folic acid (FA) is widely used to ameliorate the organ damage caused by HHCY. However, the effective dose of FA remains controversial and certain studies have suggested that FA increases the risk of cancer. Therefore, it is necessary to identify a safe, effective drug. Resveratrol (RSV) is a natural polyphenol antioxidant. Therefore, the present study explored the effects of RSV on renal damage in spontaneously hypertensive rats (SHRs) with HHCY and its potential underlying mechanism. SHRs were divided randomly into control, HHCY, HHCY + FA and HHCY + RSV groups. Blood pressure, plasma homocysteine, indexes of oxidative stress [serum malondialdehyde (MDA) and superoxide dismutase (SOD) levels] and indexes of renal function [glomerular filtration rate (GFR) and urinary albumin creatinine ratio (UACR)] were assessed. The mRNA and protein expression levels of nephrin and NAPDH oxidase (NOX)2 and NOX4 were detected via reverse transcription-quantitative PCR and western blotting. The results demonstrated that there was no significant difference in BP (blood pressure) among the groups, while the levels of homocysteine (HCY) in the HHCY intervention groups were significantly increased compared with the control. Both FA and RSV decreased the level of HCY, but the decrease was more obvious in the HHCY + FA group. Compared with the control the serum SOD levels and GFR were significantly decreased in the HHCY group, whereas the serum MDA levels and UACR were significantly increased. Moreover, the NOX2 and NOX4 expression levels were significantly increased, whereas those of nephrin were significantly decreased in the HHCY group. The changes caused by HHCY were significantly counteracted in both the HHCY + FA and HHCY + RSV groups and the antioxidant effect was markedly stronger in the HHCY + RSV group. In conclusion, RSV, like FA, potentially improved the renal function damage aggravated by HHCY in SHRs. Furthermore, RSV improved renal function mainly via the inhibition of oxidative stress. RSV may be a potential safe and effective treatment for HHCY-induced hypertensive renal damage.