%0 Journal Article
%T A Novel Synthetic Compound, Bismuth Zinc Citrate, Could Potentially Reduce Cisplatin-Induced Toxicity Without Compromising the Anticancer Effect Through Enhanced Expression of Antioxidant Protein
%A Godfrey Chi-Fung Chan
%A Hongyan Li
%A Hongzhe Sun
%A John Nicholls
%A Kwan Man
%A Runming Wang
%A Shing Chan
%J Archive of "Translational Oncology".
%D 2019
%R 10.1016/j.tranon.2019.02.003
%X Cisplatin is a common anticancer drug, but it comes with significant nephrotoxicity. Further cisplatin-induced oxidative stress contributes to the pathogenesis of the nephrotoxicity. A new compound, BiZn, can potentially prevent this complication. We verified our postulation by in vitro and in vivo models. From our findings, BiZn did not affect cisplatin-induced cytotoxicity on neuroblastoma cells under both in vitro and in vivo settings. However, BiZn significantly reduced the blood urea nitrogen and creatinine levels in cisplatin-treated mice. Under the lethal dosage of cisplatin, co-treatment of BiZn significantly increased the survival rate. BiZn stimulated antioxidant proteins metallothionein (MT) and glutathione (GSH) generation from kidney cells and minimized cisplatin-induced apoptosis. Knocking down MT-IIA and inhibiting GSH abolished such protection. In conclusion, pretreatment of BiZn decreased cisplatin-induced renal toxicity without affecting its antitumor activity. BiZn-induced antioxidant proteins MT and GSH may contribute to the renal protection effect
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6438849/