Protective effects of Panax notoginseng saponins on PME-Induced nephrotoxicity in mice.
Polymyxin E (PME) plays an important role in fighting against Gram-negative bacterial infections; however, it causes nephrotoxicity, which limits its clinical use. The aim of this study was to investigate the protective effects of a plant extract Panax notoginseng saponins (PNS) on PME-induced nephrotoxicity in mice. In vivo studies showed that PNS significantly reduced blood urea nitrogen (BUN), serum creatinine (CRE) and number of apoptotic cells in kidney, as well as renal histopathological damage which increased in the presence of PME, and suppressed PME-induced oxidative stress in kidney, as shown by the up-regulation of superoxide dismutase (SOD) and the down-regulation of malondialdehyde (MDA) levels. Furthermore, PNS inhibited the expression of Bax, while increased the expression of Bcl-2 compared to the PME-treated group. In vitro studies showed that PNS decreased intracellular reactive oxygen species (ROS) and MDA levels, increased glutathione (GSH) levels, and enhanced the activity of SOD and glutathione peroxidase (GSH-Px) in murine renal tubular epithelial cells (TCMK-1 cells). In addition, PNS enhanced cell viability and the expression of Bcl-2, restored the mitochondrial membrane potential, inhibited the expression of Bax, inhibited the activity of caspase-3 and caspase-9, and reduce apoptotic rate in PME-treated TCMK-1 cells. PNS could reduce PME-induced nephrotoxicity. The protective effects could result from inhibition of oxidative stress, and prevention of cell apoptosis via the mitochondrial pathway. These findings highlight the potential of PNS as a safe adjunct for ameliorating the nephrotoxicity.
['Zhang|Yong|Y|', 'Chi|Xiaoqing|X|', 'Wang|Zizengchen|Z|', 'Bi|Shicheng|S|', 'Wang|Yuemin|Y|', 'Shi|Fushan|F|', 'Hu|Songhua|S|', 'Wang|Huanan|H|']
D000818:Animals D017209:Apoptosis D020169:Caspases D002460:Cell Line D003091:Colistin D004365:Drugs, Chinese Herbal D004789:Enzyme Activation D005260:Female D005978:Glutathione D005979:Glutathione Peroxidase D007668:Kidney D008315:Malondialdehyde D008813:Mice, Inbred ICR D008928:Mitochondria D018384:Oxidative Stress D020011:Protective Agents D017382:Reactive Oxygen Species D012503:Saponins D013482:Superoxide Dismutase
Nephrotoxicity Polymyxin E (PME) Panax notoginseng saponins (PNS) Oxidative stress Apoptosis