Ginsenoside Rg5 Ameliorates Cisplatin-Induced Nephrotoxicity in Mice through Inhibition of Inflammation, Oxidative Stress, and ApoptosisReportar como inadecuado


Ginsenoside Rg5 Ameliorates Cisplatin-Induced Nephrotoxicity in Mice through Inhibition of Inflammation, Oxidative Stress, and Apoptosis


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1

College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, China

2

Institute of Agricultural Modernization, Jilin Agricultural University, Changchun 130118, China

3

School of Biomedical Sciences, University of Queensland, Brisbane, Queensland 4072, Australia

4

Institute of Special Wild Economic Animals and Plant, CAAS, Changchun 132109, China





*

Authors to whom correspondence should be addressed.



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. View Full-Text

Keywords: ginsenoside Rg5; cisplatin-induced nephrotoxicity; anti-oxidation; anti-inflammation; anti-apoptosis ginsenoside Rg5; cisplatin-induced nephrotoxicity; anti-oxidation; anti-inflammation; anti-apoptosis





Autor: Wei Li 1,†, Meng-Han Yan 1,†, Ying Liu 1, Zhi Liu 2, Zi Wang 1, Chen Chen 3, Jing Zhang 1,* and Yin-Shi Sun 1,4,*

Fuente: http://mdpi.com/



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