The Protective Function Of Chinese Traditional Medicine On Cisplatin-induced Nephrotoxicity

Cisplatin, a coordination complex of platinum, is one of the most effective antineoplastic agents with a wide spectrum of anticancer activity against certain human neoplasms such as tumors of the testis, ovaries, bladder, head and neck. Unfortunately the clinical use of cisplatin is limited by its dose-dependent adverse reactions such as severe nephrotoxicity and development of drug resistance in certain tumors. At present, new complex of platinum has been studied, on the other hand, new protective agents which can reduce the nephrotoxicity of cisplatin and keep the antineoplastic effects have been investigated as well.Objective: Some Chinese traditional medicine has been observed to reduce the nephrotoxicity of cisplatin and to keep the antineoplastic effects. Methods: 1. In vitro, with MTT, the growth curve of HK-2 cells and OC-3 cells had been built in order to decide the density to inoculate and when to administration. Then the damage model of ID50 is created by cisplatin and drugs are screened on it. At last, the drugs are tested if it can keep antineoplastic effects 2. With use of animal models, further test is done if the screening-drugs can reduce the nephrotoxicity of cisplatin. At first, a best concentration of cisplatin to lead to renal failure is decided, Groups of 14 rats were treated with two doses of cisplatin(2 mg/kg and 5 mg/kg, i.p.) for 7 consecutive days, second, by monitoring blood urea and serum creatinine level to choose the best drugs which either block or reduce the nephrotoxicity. 3. Search the mechanisms of drugs by measured GSH-Px level and immunocytochemistry of anti-Bcl-2 , anti-HSP70 ,anti-C-fos. Results: 1. We obtained the growth curve of HK-2 cells and OC-3 cells, in 96 well plate at the concentration of 3x10Vml, 1x104/ml, from which we conclude that the second day is appropriate for administration. 2.Cisplatin was present at a final concentration 5 umol/L which led to ID50 of HK-2 cells. From the model we choose a serial of drugs to prevent the damage of HK-2 cells. The drugs can keep the role of cisplatin to kill OC-3cells. 3.Wistar rats received 5 mg/kg (i.p.) cisplatin in single dose experiments resulted in renal damage as evidenced by increased blood urea and serum creatinine level, and on day 4, the blood urea and serum creatinine level is at the point. On the ground, Rats were treated with cisplatin (5 mg/kg,i.p.)with and without drugs for 4 or 7 days, we choosed the best drugs which either block or reduce the nephrotoxicity such as Chuanxiong, Hongcen, Tusizi, Senweitang and so on by changes in blood urea and serum creatinine level. In which QC can not only prevent but also treat the nephrotoxicity of cisplatin. Histological examination revealed treatment with cisplatin morphological signs of degeneration were largely prevented by Chuanxiong, Hongcen, Senweitang, and QC. QC can treat cisplatin nephrotoxicity well. The protective mechanisms of these candidate protective agents against the nephrotoxicity of cisplatin have not been well elucidated, but we found that the drug can rise the express of HSP70,. Hongcen, Senweitang, and QC can rise the GSH-PX level and Chuanxiong can rise the express of Bcl-2.Conclusion: Chuanxiong, Hongcen, Senweitang ,and QC can prevent cisplatin nephrotoxicity.It is worthy of researching QC further, which is hopeful to be used to prevent and. However, the protective mechanisms of these candidate protective agents against the nephrotoxicity of cisplatin have not been well elucidated.