Pioglitazone ameliorates ischemia/reperfusion-induced acute kidney injury via oxidative stress attenuation and NLRP3 inflammasome

Abstract

Acute kidney injury (AKI) induced by renal ischemia/reperfusion injury (IRI) is a severe clinical condition. ROS accumulation, antioxidant pathways deficiency, and inflammation are involved in IRI. Pioglitazone (Pio) exerts anti-inflammatory and antioxidant effects. The aim of this study was to explore the protective effects of pioglitazone against IRI-induced AKI. Pathogen-free Sprague–Dawley (SD) rats were arbitrarily divided into four groups: Sham operation group Control (CON) group, CON + Pio group, I/R + Saline group, and I/R + Pio group. In addition, HK-2 cells were subjected to hypoxia and reoxygenation to develop an H/R model for investigation of the protective mechanism of Pio. Pretreatment with pioglitazone in the model rats reduced urea nitrogen and creatinine levels, histopathological scores, and cytotoxicity after IRI. Pioglitazone treatment significantly attenuated renal cell apoptosis, decreased cytotoxicity, increased Bcl-2 expression, and downregulated Bax expression. Besides, the levels of ROS and inflammatory factors, including NLRP3, ASC, pro-IL-1β, pro-caspase-1, cleaved-caspase-1, TNF-α, IL-6, and IL-1β, in I/R rats and H/R cells were normalized by the pioglitazone treatment. Pioglitazone improved IRI-induced AKI by attenuating oxidative stress and NLRP3 inflammasome activation. Therefore, pioglitazone has the potential to serve as a novel agent for renal IRI treatment and prevention.