title: Ginsenoside Rg5 Ameliorates Cisplatin-Induced Nephrotoxicity in Mice through Inhibition of Inflammation, Oxidative Stress, and Apoptosis.
abstract: Although cisplatin is an effective anti-cancer agent that is widely used for treating various types of malignant solid tumors, the nephrotoxicity induced by cisplatin severely limits its clinical application. The present study was designed to explore the potential protective effect of ginsenoside Rg5, a rare ginsenoside generated during steaming ginseng, on cisplatin-induced nephrotoxicity in a mouse experimental model. The possible mechanisms underlying this nephroprotective effect were also investigated for the first time. Rg5 was given at doses of 10 and 20 mg/kg for 10 consecutive days. On Day 7, a single nephrotoxic dose of cisplatin (25 mg/kg) was injected to mice. Cisplatin administration resulted in renal dysfunction as evidenced by increase in serum creatinine (CRE) and blood urea nitrogen (BUN) levels. In addition, cisplatin increased the level of malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE), the makers of lipid peroxidation, and depleted glutathione (GSH) content and superoxide dismutase (SOD) activity in renal tissues. These effects were associated with the significantly increased levels of cytochrome P450 E1 (CYP2E1), 4-hydroxynonenal (4-HNE), tumor necrosis factor (TNF)-α, interleukin (IL)-1β, nuclear factor-kappa B (NF-κB) p65, and cyclooxygenase-2 (COX-2) in renal tissues. However, pretreatment with ginsenoside Rg5 significantly attenuated the renal dysfunction, oxidative stress and inflammation response induced by cisplatin. Furthermore, ginsenoside Rg5 supplementation inhibited activation of apoptotic pathways through increasing Bcl-2 and decreasing Bax expression levels. Histopathological examination further confirmed the nephroprotective effect of Rg5. Collectively, these results clearly suggest that Rg5-mediated alleviation of cisplatin-induced nephrotoxicity may be related to its anti-oxidant, anti-apoptotic and anti-inflammatory effects.
authors.affiliation: College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, China. liwei7727@126.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, China. ymhan@jlau.edu.cn.
authors.forename: Meng-Han
authors.initials: MH
authors.lastname: Yan
authors.affiliation: College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, China. y.liu@jlau.edu.cn.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Institute of Agricultural Modernization, Jilin Agricultural University, Changchun 130118, China. lzhiiu@126.com.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Liu
authors.affiliation: College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, China. wangzi8020@126.com.
authors.forename: Zi
authors.initials: Z
authors.lastname: Wang
authors.affiliation: School of Biomedical Sciences, University of Queensland, Brisbane, Queensland 4072, Australia. Chen.chen@uq.edu.au.
authors.forename: Chen
authors.initials: C
authors.lastname: Chen
authors.affiliation: College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, China. zhjing0701@163.com.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, China. sunyinshi2002@126.com.|Institute of Special Wild Economic Animals and Plant, CAAS, Changchun 132109, China. sunyinshi2002@126.com.
authors.forename: Yin-Shi
authors.initials: YS
authors.lastname: Sun
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002945:Cisplatin / Q000633:toxicity*; D003432:Cross-Linking Reagents / Q000633:toxicity; D005260:Female; D036145:Ginsenosides / Q000494:pharmacology*; D007249:Inflammation / Q000139:chemically induced* / Q000188:drug therapy; D007668:Kidney / Q000187:drug effects; D007674:Kidney Diseases / Q000139:chemically induced* / Q000188:drug therapy; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D018384:Oxidative Stress / Q000187:drug effects*; D005894:Panax / Q000737:chemistry; D018515:Plant Leaves / Q000737:chemistry; D018547:Plant Stems / Q000737:chemistry
chemical_list: D003432:Cross-Linking Reagents; D036145:Ginsenosides; C572381:ginsenoside Rg5; D002945:Cisplatin
keywords: anti-apoptosis; anti-inflammation; anti-oxidation; cisplatin-induced nephrotoxicity; ginsenoside Rg5