Pinostrobin attenuates colistin-induced apoptosis of human renal proximal tubular cells

Abstract

Colistin is one of the last-resort antibiotics used to treat multidrug-resistant (MDR) gram-negative bacterial infection. However, this drug causes nephrotoxicity by inducing oxidative stress and mitochondrial impairment of renal proximal tubular cells. Pinostrobin, which is a major natural bioactive compound isolated from Boesenbergia rotunda, has anti-oxidative properties and preventive effects on mitochondrial damage. Therefore, this study aimed to investigate the protective effects of pinostrobin against colistin-induced toxicity in human renal proximal tubular (RPTEC/TERTl) cells. Treatment of colistin (200 µg/ml) significantly reduced cell viability and increased apoptotic cells compared with vehicle treatment. These effects were attenuated by co-treatment with pinostrobin (50–100 µM). Colistin-induced apoptosis was correlated with increased ROS and cytochrome c expression accompanied by reduction in mitochondrial membrane potential and anti-apoptotic protein (Bcl-2) expression. These effects were abolished by co-treatment with pinostrobin. Collectively, pinostrobin has protective effects against colistin-induced apoptosis of RPTEC/TERT1 cells by improving oxidative status and mitochondrial function.