Bismuth Compounds as Novel Antagonists Against Toxicity of Cisplatin

Abstract

Cisplatin is one of the most effective anticancer drugs. However, it suffers severe side effects, in particular nephrotoxicity. Some metallo-compounds, such as zinc sulphate and Bi(NO3)3 were found to be able to reduce the toxicity of cisplatin. However they suffer from low in vivo efficacy and there lacks large-scale pre-clinical evaluation on their effectiveness. We designed and synthesized a series of bismuth compounds for reduction of side effects of cisplatin. Among them, BicitZ, Bi-L1 and Bi-L12 were screened out and exert excellent nephroprotective activity under both in vitro and in vivo conditions. We also found the pre-administration of Bi-L1, Bi-L12 and BicitZ exerts negligible effects on cisplatin’s anti-cancer activity in the tumor-engrafted mice. Several key proteins with altered expression levels in response to bismuth compounds and/or cisplatin treatment were identified and would be used for further function validation. Our work may offer an effective alternative of nephroprotective agent for alleviating the side effect of cisplatin treatment in human. We thank the Innovation Technology Commission of HKSAR (ITS/085/14) and the University of Hong Kong for financial support. References [1] Lloyd, K; Nat. Rev., 2007, 7, 573-584 [2] Wang, D; Lippard, SJ, Nat. Rev. Drug Discov., 2005, 4, 307-320 [3] Satoh, M., Aoki, Y., Tohyama, C. Cancer. Chemoth. Pharm.,1997, 40, 358