The pseudoginsenoside F11 ameliorates cisplatin-induced nephrotoxicity without compromising its anti-tumor activity in vivo.

Abstract

The clinical use of cisplatin was severely limited by its associated nephrotoxicity. In this study, we investigated whether the pseudoginsenoside F11 had protective effects against cisplatin-induced nephrotoxicity. To clarify it, one in vivo model of cisplatin-induced acute renal failure was performed. The results showed that pretreatment with F11 reduced cisplatin-elevated blood urea nitrogen and creatinine levels, as well as ameliorated the histophathological damage. Further studies showed that F11 could suppress P53 activation, inverse the ratio of Bax/Bcl2 and the anti-oxidative and free radical levels induced by cisplatin, which in turn inhibited tubular cell apoptosis. Importantly, F11 enhanced rather than inhibited the anti-tumor activity of cispaltin in murine melanoma and Lewis lung cancer xenograft tumor models. Our findings suggested that administering F11 with cisplatin might alleviate the associated nephrotoxicity without compromising its therapeutic efficiency. This finding provides a novel potential strategy in the clinical treatment of cancer.

• Authors: Hongbo Wang, Liang Kong, Jianqiao Zhang, Guohua Yu, Guangyao Lv, Fangxi Zhang, Xiaoguang Chen, Jingwei Tian, Fenghua Fu
• Journal: Scientific reports (Sci Rep) Vol. 4 Pg. 4986 (May 16 2014) ISSN: 2045-2322 [Electronic] England
• PMID: 24832194 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Apoptosis Regulatory Proteins
• Ginsenosides
• pseudoginsenoside F11
• Cisplatin

Topics

• Acute Kidney Injury (chemically induced, metabolism)
• Animals
• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Apoptosis Regulatory Proteins (metabolism)
• Carcinoma, Lewis Lung (drug therapy, metabolism)
• Cisplatin (adverse effects)
• Ginsenosides (pharmacology)
• Kidney Tubules (drug effects, metabolism)
• Male
• Melanoma (drug therapy, metabolism)
• Mice
• Mice, Inbred C57BL
• Rats
• Rats, Sprague-Dawley
• Xenograft Model Antitumor Assays (methods)