Hepatotoxicity and pharmacokinetics of cisplatin in combination therapy with a traditional Chinese medicine compound of Zengmian Yiliu granules in ICR mice and SKOV-3-bearing nude mice

BMC Complementary and Alternative Medicine

Research Article

Hong Yang¹  Cong Qi¹  Lin Qian¹  Hai Wei²  Wen-bin Zhou²  Chang-hong Wang³  Li-li Ji³  Can Gong⁴ 

[1] Department of Gynaecology, Shanghai Shuguang Hospital Affiliated with Shanghai University of Traditional Chinese Medicine, 528 Zhang Heng Road, Zhangjiang Hi-Tech Park, 201203, Shanghai, People's Republic of China;Research Center for Traditional Chinese Medicine and Systems Biology, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Zhangjiang Hi-Tech Park, 201203, Shanghai, People's Republic of China;The Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, The Ministry of Education (MOE) Key Laboratory for Standardization of Chinese Medicines and Shanghai Key Laboratory of TCM Complex Prescription, 1200 Cailun Road, Zhangjiang Hi-Tech Park, 201203, Shanghai, People's Republic of China;The Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, The Ministry of Education (MOE) Key Laboratory for Standardization of Chinese Medicines and Shanghai Key Laboratory of TCM Complex Prescription, 1200 Cailun Road, Zhangjiang Hi-Tech Park, 201203, Shanghai, People's Republic of China;School and Chemical and Environmental Engineering, Shanghai Institute of Techanology, 100 Haiquan Road, 201418, Shanghai, Fengxian, People's Republic of China;

关键词: Cisplatin;    Hepatotoxicity;    Pharmacokinetics;    Zengmian Yiliu granule;   

DOI  :  10.1186/s12906-015-0799-9

 received in 2015-04-02, accepted in 2015-08-03,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundCisplatin (CDDP) is a highly effective chemotherapeutic agent used for therapy of many tumors and has been limited by its toxicity. Zengmian Yiliu granule (ZMYL), a compound preparation of traditional Chinese medicines, has been used in clinic as a complementary and alternative medicine for attenuating CDDP-induced toxicities and enhancing the tumor therapeutic effect of CDDP. The aim of the present study is to investigate hepaprotective effect of ZMYL against CDDP-induced hepatotoxicity. Further, the pharmacokinetic characteristics of CDDP in SKOV-3-bearing nude mice were observed.MethodsThe ICR mice were dosed orally with ZMYL for 7 days and then CDDP was injected intraperitoneally at a dose of 45 mg/kg body weight. The serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were measured to evaluate the liver function. The total glutathione (T-GSH), reduced glutathione (GSH) and glutathione S-transferase (GST) levels were determined to evaluate the oxidant damage in liver homogenates. Tissue pathological change in liver was conducted by light microscopy analysis. The pharmacokinetic and tissue distribution of free and total platinum (Pt) after dosing of CDDP alone and combination with ZMYL were determined in SKOV-3-bearing nude mice by ICP-MS.ResultsOral administration of ZMYL prior to the CDDP treatment could prevent the CDDP-induced in lifting of ALT and AST, reduction of T-GSH, R-GSH and GST, and some histopathological alterations in ICR mice. Some differences in pharmacokinetic parameters between the two groups have been observed in higher CL and decreased MRT of free platinum (Pt) in plasma and total Pt in spleen in CDDP co-administration with ZMYL group. It indicated CDDP was cleared more quickly from blood and spleen, and could reduce the accumulation and toxic possibility of CDDP in combination with ZMYL.ConclusionsZMYL could be used as a beneficial supplement, which could attenuate CDDP-induced hepatotoxicity during CDDP chemotherapy and did not disturb the pharmacokinetics fate of CDDP significantly.

【 授权许可】

CC BY   
© Gong et al. 2015