Suppression of glomerular damage, inflammation, apoptosis, and oxidative stress of acute kidney injury induced by cyclophosphamide toxicity using resveratrol in rat models.

ABSTRACT

Cyclophosphamide (CP) is a chemotherapy drug that can be used to treat different types of cancers, but its nephrotoxicity effects restrict its usage in clinical settings. Currently, we examined whether the polyphenolic antioxidant and anti-inflammatory compound, resveratrol (RES), can protect against CP-induced nephrotoxicity. Twenty male mature Sprague-Dawley rats were divided into 4 groups of equal size control group, RES group which received RES (20 mg/kg) for 15 consecutive days, CP group which received CP as a single dose (150 mg/kg) on day 16, and CP+RES group which was similar of the RES and CP groups. Tissue samples were obtained for the stereological, immunohistochemical, biochemical, and molecular evaluations. Findings showed that the numerical density of glomerulus, total volumes and interstitial tissue volumes of kidney, antioxidative biomarkers concentrations (CAT, GSH, SOD), and expression levels of OCT2 gene were notably greater in the CP+RES group than the CP group (P<0.05). During treatment, there was a significant decrease in the serum levels of the urea and creatinine, the densities of apoptotic and inflammatory cells, as well as levels of MDA and proinflammatory cytokines (IL-1ß, TNF-α, and PFN1) in the CP+RES group than the CP group (P<0.05). We deduce that giving RES can suppress of glomerular damage, inflammation, apoptosis, and oxidative stress of acute kidney injury induced by CP toxicity.