| DOI: 10.29090/psa.2021.06.21.008 | Pharm Sci Asia 2021; 48(6), 549-556 |
Pinostrobin attenuates colistin-induced apoptosis of human renal proximal tubular cellsNichakorn Worakajit1, Penjai Thongnuanjan2, Napason Chabang3, Sirima Soodvilai4, Patoomratana Tuchinda5, Sunhapas Soodvilai1,5*
1 Research Center of Transporter Protein for Medical Innovation, Department of Physiology, Faculty of Science, Mahidol University, Bangkok, Thailand
2
Toxicology Graduate Program, Multidisciplinary Unit, Faculty of Science, Mahidol University, Bangkok, Thailand
3
School of Bioinnovation and Bio-based Product Intelligence, Faculty of Science, Mahidol University, Bangkok, Thailand
4
Department of Pharmaceutical Technology, Faculty of Pharmacy, Rangsit University, Pathumthani, Thailand
5
Excellent Center for Drug Discovery, Mahidol University, Bangkok, Thailand
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/TERT1) 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.
Keyword:
Colistin, Mitochondrial dysfunction, Nephrotoxicity, Pinostrobin, Renal proximal tubular cell
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