摘要：SummaryCisplatin (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 roleviametallothionein-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.Graphical AbstractDisplay OmittedHighlights•Bi(TPP), a potent nephroprotectant against cisplatin-induced toxicity, is disclosed•Protective potency of Bi(TPP) could be modulated by varying lipophilic TPP ligands•Bi(TPP) ameliorates cisplatin-induced renal damage via multiple mechanisms•Combined therapy with Bi(TPP) does not compromise the antitumor efficacy of cisplatinInorganic Chemistry; Organometallic Chemistry; Medical Biochemistry
