Antioxidant, Anti-Apoptotic, and Anti-Inflammatory Effects of Farrerol in a Mouse Model of Obstructive Uropathy.

Abstract

Obstructive uropathy is a clinical condition that can lead to chronic kidney disease. However, treatments that can prevent the progression of renal injury and fibrosis are limited. Farrerol (FA) is a natural flavone with potent antioxidant and anti-inflammatory properties. Here, we investigated the effect of FA on renal injury and fibrosis in a mouse model of unilateral ureteral obstruction (UUO). Mice underwent a sham or UUO operation and received intraperitoneal injections of FA (20 mg/kg) daily for 8 consecutive days. Histochemistry, immunohistochemistry and immunofluorescence staining, TdT-mediated dUTP nick end labeling assay, Western blotting, gene expression analysis, and biochemical tests were performed. FA attenuated renal dysfunction (p < 0.05) and ameliorated renal tubular injury (p < 0.01) and interstitial fibrosis (p < 0.001) in UUO mice. FA alleviated 4-hydroxynonenal expression (p < 0.001) and malondialdehyde levels (p < 0.01) by regulating pro-oxidant and antioxidant enzymes. Apoptosis in the kidneys of UUO mice was inhibited by FA (p < 0.001), and this action was accompanied by decreased expression of cleaved caspase-3 (p < 0.01). Moreover, FA alleviated pro-inflammatory cytokine production (p < 0.001) and macrophage infiltration (p < 0.01) in the kidneys of UUO mice. These results suggest that FA ameliorates renal injury and fibrosis in the UUO model by inhibiting oxidative stress, apoptosis, and inflammation.