Time-course inhibition evaluation of renal fibrosis with bardoxolone methyl in unilateral ureteral obstruction

Abstract

Abstract Purpose: Reactive oxygen species can aggravate of renal fibrosis, resulting in the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) as a biological defense factor. Nrf2 exerts a renoprotective effect by producing antioxidant response elements (AREs) that antagonize renal fibrosis. Recently, bardoxolone methyl (BARD), an Nrf2 activator, has attracted attention as a therapeutic agent for chronic kidney disease. We conducted a time course renoprotective evaluation of BARD administration among rats with unilateral ureteral obstruction (UUO)-induced renal injury. Materials and methods: Male Sprague Dawley rats which underwent UUO received BARD for 2 weeks postoperatively to investigate its renoprotective effect using quantitative real-time polymerase chain reaction (RT-PCR) and histopathological analyses of kidney samples. Results: Compared with UUO, BARD administration reduced interstitial fibrotic area, causing a substantial decline in the frequency of ED-1–positive cells and the TGF-β area. RT-PCR also showed that BARD administration suppressed the expression of renal fibrotic factors and promoted AREs. Moreover, immunostaining for Nrf2 showed that BARD administration enhanced its activation and translocation to the nucleus. Conclusions: Our results suggest that BARD induces nuclear activation of Nrf2 to activate AREsover time and enhances renal protection against inflammation and fibrosis caused by UUO.