Journal
TRANSLATIONAL ONCOLOGY
Volume 12, Issue 5, Pages 788-799Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.tranon.2019.02.003
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Funding
- Innovation Technology Commission of HKSAR [ITS/085/14]
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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.
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