Nephroprotective effect of β-sitosterol on N-diethylnitrosamine initiated and ferric nitrilotriacetate promoted acute nephrotoxicity in Wistar rats

Abstract

BACKGROUND: The most abundant plant sterol β-sitosterol is widely used for treating heart diseases and chronic inflammatory conditions. The objective of the current study was to evaluate the nephroprotective effect of β-sitosterol against nephrotoxicants which were studied using renal function markers, antioxidant and lipid peroxidation status, and inflammatory markers. METHODS: Male albino Wistar rats were randomly grouped into four: group 1 was vehicle control rats (0.1% carboxymethyl cellulose [CMC]); group 2 was rats treated with N-diethylnitrosamine (DEN) (200 mg/kg body weight [bw] i.p. on the 15th day) and ferric nitrilotriacetate (Fe-NTA) (9 mg/kg bw i.p. on 30th and 32nd days); group 3 was rats that received β-sitosterol (20 mg/kg bw in 0.1% CMC, p.o. for 32 days) 2 weeks prior to the exposure to the nephrotoxicant; and group 4 was rats that received β-sitosterol alone. The experiment was terminated after the 24 h of last dosage of Fe-NTA, and all the animals were sacrificed. The blood, liver and kidney from each group were analyzed for biochemical, molecular and histological changes. RESULTS: All the parameters showed significant changes in DEN and Fe-NTA treated animals, whereas β-sitosterol pretreated animals' altered biochemical parameters were restored to near normal. Histopathological and immunoexpression studies on tissues also corroborate the biochemical endpoints. CONCLUSIONS: Administration of β-sitosterol to nephrotoxicity induced rats showed significant positive changes in biochemical parameters, histopathological and immunohistochemical observations, and up-regulation of Nrf2 gene expression. From this, it was clear that β-sitosterol showed renal protective function.