| Cisplatin (DDP) is an anticancer drug used widely in chemotherapy and has potent antineoplastic activity against various malignant tumors, but the advantage of Cisplatin is accompanied by a lot of side effects, such as nephrotoxicity and hematological toxicity. Nephrotoxicity is commonly identified as the major dose-limiting factor. At present, nephrotoxicity has been extensively researched, but there is little information dealing with the effects of DDP on apopotosis, apoptosis-related gene expression, inducible nitric oxide synthase (iNOS) and nitric oxide (NO) in renal cortex and erythropoietin (Epo) primarily produced by the kidney. It is reported that some Chinese Medicine have effects on antineoplastic treatment and distinctive advantages of protecting against side-effect brought about by the chemoterapy as well. So far accomplishment has been made in the field of application of Chinese Medicine to protecting against toxin and side-effect induced by anticancer drugs, but the research on Chinese Medicine used to protect and cure anaemia caused by DDP has not been found yet. In this experiment the anemia and nephrotoxicity in rats were induced by DDP, and their mechanisms of were analysed, we also made use of the Chinese Medicine which is good for energy and enriches kidney to control or reduce cisplatin-induced nephrotoxicity and anemia, furthermore we sorted out specific Chinese Medicine which could increase the level of Epo and decrease the toxin in blood and kidney in hope of providing promising drugs for chemotherapy. If the experiment is successful, the research will be applied widely for its economic and social benefit.The researches have been made in this experiment1) A study of the mechanism of cisplatin-induced nephrotoxicity in ratsTo explore the role of apopotosis, apoptosis-related gene expression, iNOS and NO in renal cortex in oxidative stress mechanisms in DDP-induced kidney damage in rats. Nephrotoxicity was induced with single intravenous (iv) injection of DDP of8mg/kg body weight. Serum creatinine (Cr), blood urea nitrogen (BUN), kidney apopotosis, apoptosis-related gene expression, malondialdehyde (MDA), glutathione (GSH) and NO levels, iNOS and superoxide dismutase (SOD) activities, platinum content were measured1,3,5and7days after administration of the anticancer drugs. Moreover, the changes of renal tissue were examined by light and eletron microscope. Male Sprague-Dawley rats, treated with cisplatin, developed nephrotoxicity, as demonstrated by increased serum Cr and BUN. Cisplatin also produced a significant increase in apoptosis rate, expression of Bax and P53, and decrease in expression of Bcl-2in the kidney. There are a correlation between apoptosis and expression of Bcl-2, Bax and P53. Pathological examination revealed that DDP induces apoposis and necrosis in the rat kidney. These data indicate that Bcl-2, Bax and P53are significant genes in modulating the cisplatin-induced apoptosis which may play an important role in the development of DDP-induced nephrotoxicity. Furthermore, the impairment in kidney function was accompanied by an increase in MDA, NO and platinum content, iNOS activity, a decrease in GSH content, and SOD activities in kidney tissue. These observations also indicated that oxidative damage is one of the mechanisms of toxic effects on kidney induced by DDP. The increase of the productions of NO by increasing the activities of iNOS was related to the nephrotoxicity induced by DDP, thus NO maybe play an important role in nephroloxicity induced by DDP.2) Protective effects of Yiqi Jianpi Bushen recipe(益气健脾补肾方)against cisplatin-induced nephrotoxicity in rats.The aim of this study was to the investigate protective effects of different doses of Yiqi Jianpi Bushen recipe(益气健脾补肾方)on cisplatin-induced nephrotoxicity in rats. Cisplatin (8mg/kg) was intravenously injected as a single dose and Yiqi Jianpi Bushen recipe at different doses (10.8g/kg/day,21.6g/kg/day,30.4g/kg/day) was administered by gavage. The concentrations of Cr and BUN in plasma, levels of MDA, NO and platinum content as well as SOD and iNOS activities were determined in kidney tissue. Moreover, the effect of Yiqi Jianpi Bushen recipe on the antineoplastic activity of DDP was measured in mice bearing S180. A single dose of cisplatin caused kidney damage manifested by increases in plasma Cr and BUN levels. Treatment with medium dose of the herbs attenuated the increases in plasma Cr and BUN, tissue MDA and NO levels, and iNOS activity. Medium dose of the herbs also reduced depletion in the tissue SOD activity. Yiqi Jianpi Bushen recipe treatment did not result in any observable loss in anti-tumor activity of DDP.Results from this study indicate that the proper dose of the herbs might have protective effect against cisplatin-induced nephrotoxicity in rat and Yiqi Jianpi Bushen recipe would not interfere with the antitumor action of DDP for S180sarcoma.3) Changes of serum erythropoietin cisplatin-induced anemia in rats.There are conflicting data about the effects of DDP on Epo response to anemia. The Aim of the present work was to investigate changes of serum Epo during cisplatin-or5-Fluorouracil-induced anemia in rats in comparison to the anemic rats with5-Fluorouracil (5-Fu) treated. Anemia was induced with single intravenous (iv) injection of DDP of8mg/kg body weight or5-Fu of150mg/kg body weight. Serum Epo, haemoglobin (Hb), blood urea nitrogen (BUN) concentration and reticulocyte (Ret) counts were measured7,21,35and49days after administration of the anticancer drugs. The changes of renal tissue were examined by light and electron microscope. A single injection of5-Fu decreased Ret counts and Hb concentration but increased Epo levels of serum.5-Fu had little effect on BUN. No evident morphological abnormalities were found by light and electron microscopy in5-Fu-treated rats. A single injection of DDP decreased Ret counts and Hb concentration but increased BUN. Serum Epo decreased on the7days but increased on the21days after DDP treatment, however serum Epo elevation was modest. Pathological examination revealed that DDP caused significant renal damage in rats. These results suggest that in5-Fu-induced anemia, the elevated serum Epo level was due to the feed-back response to anemia. In DDP-induced anemia, the degree of elevated serum Epo level was low compared with the extent to which anemia was. So nephrotoxicity of cisplatin-induced rats might be the main cause of changes of serum Epo.4) Effects of Yiqi Jianpi Bushen recipe (益气健脾补肾方) on cisplatin-induced anemia in rats.The aim of this study was to investigate the effects of Yiqi Jianpi Bushen recipe(益气健脾补肾方) on cisplatin-induced anemia in rats. Cisplatin (8mg/kg) was intravenously injected as a single dose and Yiqi Jianpi Bushen recipe at different doses (10.8g/kg/day,21.6g/kg/day,30.4g/kg/day) was administered by gavage. Serum Epo, Hb, BUN concentration and Ret counts were measured7,21,35and49days after administration of the anticancer drugs. The changes of renal tissue were examined by light and electron microscope. Medium dose of the herbs could increase Hb and serum Epo levels, and reduce the content of BUN in rats that suffered from cisplatin-induced anemia. Pathological examination revealed the protective effect of the herbs on the kidneys of the rats. These results show that the proper dose of the herbs could minimize the suppression of Epo and antagonize the kidney damage induced by DDP, thus having good inhibitory effects on cisplatin-induced anemia in rats. |
PDF Full Text Request