OBJECTIVE: Although cisplatin has been used as a key drug for standard anticancer treatment, it is known that nausea and vomiting, renal injury occur frequently as a side effect.
Cisplatin is also known to be excreted via the multidrug and toxin release (MATE) transporter, and the involvement of the MATE transporter in cisplatin-induced kidney injury has been reported. On the other hand, the MATE transporter is also involved in the excretion of ondansetron, a 5-HT₃ receptor antagonist used as an antiemetic, but the effects of various 5-HT₃ receptor antagonists currently used clinically on cisplatin-induced renal injury has not been elucidated. Therefore, in this study, the effect of various 5-HT₃ receptor antagonists on cisplatin-induced renal injury was examined.
METHOD: In order to establish cisplatin‐induced AKI, C57BL/6 mice were intraperitoneally administered with cisplatin or saline. Various 5-HT₃ receptor antagonists were administered 30 minutes before administration of cisplatin. Renal function was evaluated by serum creatinine and BUN. Histological damage in the cortex of HE‐stained kidney sections was scored. The changes in the number of reported renal injuries due to the combination of cisplatin and various 5-HT₃ receptor antagonists was analyzed by FAERS.
RESULT : The concomitant use of ondansetron significantly increased cisplatin accumulation in the kidney and significantly worsened renal damage. On the other hand, there was no worsening of renal function in the palonosetron combination group compared to the cisplatin alone group.
FAERS analysis revealed that the combination of cisplatin and first-generation 5-HT₃ receptor antagonists resulted in a significant increase in the number of reported renal injuries.
CONCLUSION : These results suggest that the second generation 5-HT₃ receptor antagonist may have less effect on cisplatin‐induced AKI than the first generation.