Bismuth Porphyrin Antagonizes Cisplatin-Induced Nephrotoxicity via Unexpected Metallothionein-Independent Mechanisms

iScience

Yuchuan Wang¹  Hongzhe Sun¹  Yufeng Zhang²  Runming Wang²  Suyu Wang²  Hongyan Li³  Shing Chan³  Zhong Zuo⁴  Godfrey Chi-Fung Chan⁴ 

[1] Adolescent Medicine, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam Road, Pok Fu Lam, Hong Kong S.A.R., P.R. China;Department of Chemistry, The University of Hong Kong, Pokfulam Road, Pok Fu Lam, Hong Kong S.A.R., P.R. China;;Department of Paediatrics &School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong S.A.R., P.R. China;

关键词: Inorganic Chemistry;    Organometallic Chemistry;    Medical Biochemistry;   

DOI  :  

来源: DOAJ

【 摘 要 】

Summary: Cisplatin (CDDP) has been a highly successful anticancer drug in cancer therapy; however, its further application suffers severe nephrotoxicity. Herein, we identify bismuth tetraphenylporphyrinate [Bi(TPP)] as a potent protective agent against CDDP-induced nephrotoxicity. Bi(TPP) attenuates CDDP-induced acute kidney injury and prevents the death of mice exposed to a lethal dose of CDDP. The protective potency of bismuth porphyrin complexes could be optimized by varying lipophilic TPP ligands with ideal ClogP values of 8–14. Unexpectedly, Bi(TPP) exhibited a protective role via metallothionein-independent pathways, i.e., maintenance of redox homeostasis and energy supplement, elimination of accumulated platinum in the kidney, and inactivation of caspases cascade in apoptotic pathway. Significantly, Bi(TPP) does not compromise the antitumor activity of CDDP in the orthotopic tumor xenograft mouse model. These findings suggest that Bi(TPP) could be incorporated into current CDDP-based cancer therapy as a nephroprotective agent.

【 授权许可】

Unknown