Nephroprotective potential of Panduratin A against colistin-induced renal injury via attenuating mitochondrial dysfunction and cell apoptosis

Biomedicine & Pharmacotherapy

Promsuk Jutabha¹  Virawudh Soontornniyomkij¹  Patoomratana Tuchinda²  Soraya Chaturongakul³  Nichakorn Worakajit⁴  Natechanok Thipboonchoo⁴  Sunhapas Soodvilai⁴ 

[1] Chakri Naruebodindra Medical Institute, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bang Phli, Samut Prakan 10540, Thailand;Excellent Center for Drug Discovery, Mahidol University, Bangkok 10400, Thailand;Institute of Molecular Biosciences, Mahidol University, Nakhon Pathom 73170, Thailand;Research Center of Transporter Protein for Medical Innovation, Department of Physiology, Faculty of Science, Mahidol University, Bangkok 10400, Thailand;

关键词: Panduratin A;    Colistin;    Renal proximal tubular cells;    Nephrotoxicity;    Mitochondrial impairment;    Oxidative stress;   

DOI  :  

来源: DOAJ

【 摘 要 】

Colistin is a last-resort polypeptide antibiotic widely used to treat against multidrug-resistant Gram-negative bacterial infections. However, this treatment is associated with nephrotoxicity. The aim of this study was to examine the potential protective effect of panduratin A, a bioactive compound of Boesenbergia rotunda, on colistin-induced nephrotoxicity in both in vivo and in vitro models. Intraperitoneal injection of 15 mg/kg colistin for 7 days markedly promoted renal tubular degeneration, increased blood urea nitrogen (BUN) levels, and upregulated the expression of renal injury biomarker and apoptosis proteins. In addition, treatment with colistin increased oxidative stress and apoptosis in mice kidney tissues. Interestingly, these defects were attenuated when co-administered of colistin with panduratin A (2.5 or 25 mg/kg). The underlying mechanisms of panduratin A attenuating colistin toxicity was investigated in human renal proximal tubular cells (RPTEC/TERT1). The mechanisms by which colistin-triggered cytotoxicity was determined by analysis of cell death, reactive oxygen species (ROS) levels, mitochondria function as well as the expression of proteins related to apoptosis pathway. Colistin treatment (200 µg/ml) significantly increased cell apoptosis, elevated ROS production, reduced mitochondrial membrane potential, and decreased anti-apoptotic protein (Bcl-2) expression. These effects were notably suppressed by co-treatment with panduratin A (5 μM). Collectively, panduratin A exerts as a novel nephroprotective agent to protect against colistin-induced renal injury by attenuating mitochondrial damage and renal cell apoptosis.

【 授权许可】

Unknown