Host: The Japanese Society of Toxicology
Name : The 50th Annual Meeting of the Japanese Society of Toxicology
Date : June 19, 2023 - June 21, 2023
Warfarin is an anticoagulant that suppresses vitamin K-dependent coagulation factor production by competitively inhibiting VKOR and has been used as rodenticide. Abuse of warfarin-based rodenticides led to the emergence of resistant rodents, which became difficult to control. Second-generation rodenticides were developed based on warfarin with improved toxicity, but its cumulative effect has caused death of wild animals. Therefore, a new rodenticide that is effective against resistant rodents and has high environmental safety is needed. The objective of this study was to compare the properties of geometric isomers of second-generation rodenticides since it was reported that the half-lives in vivo differ significantly among these geometric isomers. In this study, geometric isomers of five major second-generation rodenticides were isolated and subjected to VKOR inhibition assays using cultured cells and in silico VKOR-rodenticide molecular docking. The results showed that bromadiolone and difethialone showed lower IC50 values for their trans form, while the other three substances showed lower IC50 values for their cis form. However, all substances and isomers showed more potent VKOR inhibitory activity than warfarin, and there were no significant differences in binding and inhibitory activity against VKOR between the cis and trans isomers. The differences in pharmacokinetics of the two isomers may be due to albumin binding and P450 metabolism rather than VKOR binding.
