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Cisplatin (cis-diamminedichloroplatinum, CDDP) is one of the most potentanticancer drugs. However, the therapeutic value of CDDP is greatly compromisedby its dose-limiting nephrotoxicity. This study was performed to investigate whetherreduced glutathione (GSH) was able to reduce the kidney injury induced by CDDPand whether it affected the anticancer activity of CDDP in vivo and in vitro.In in vivo experiments, mice were divided into five groups: control, CDDP onlyand three GSH treatment groups. Blood samples were collected 72 h after CDDP administrationto determine the levels of blood urea nitrogen (BUN) and plasma creatinine (Cr).In addition, we examined antioxidative parameters, malondialdehyde (MDA) levelsand histopathological changes in the kidney. In order to investigate whether GSHaffected the anticancer activity of CDDP, we performed a sulforhodamine B (SRB)assay to determine the anti-proliferative effect in three tumor cell lines oftreatment with CDDP alone or combined with GSH and examined the cell morphology.The results revealed that GSH decreased the BUN and Cr levels in plasma, amelioratedthe pathological changes induced by CDDP and enhanced the endogenous antioxidantcapacities in all three GSH groups. Furthermore, GSH significantly inhibited thegrowth of the three tumor cell lines when combined with CDDP and did not affectthe inhibitory effect of CDDP on the carcinoma cell proliferation. In addition,we found no differences among the three GSH groups. These findings suggest thatGSH is able to attenuate the nephrotoxicity induced by CDDP, not only when administeredprior to CDDP, but also when administered at the same time as or subsequent toCDDP administration, without affecting the anticancer activity of CDDP. Thus,the administration of GSH is a promising approach for attenuating the nephrotoxicitycaused by CDDP.

Evaluation of the effect of glutathione on cisplatin antitumor activity and kidney injury at different administration times