Abstract
[Introduction]
Anticoagulant rodenticides (ARs) have been used for control of rodents’ population. ARs inhibit vitamin K epoxide reductase (VKOR) playing role in producing clotting factors, which results in lethal hemorrhage in rodents. However, ARs-spread have caused accidental death to non-target species. Thus, it is necessary for proper usage of ARs to evaluate sensitivity of wild species. In Japan, ARs were used in Bonin (Ogasawara) islands. Bonin fruit bat (Pteropus pselaphon) is the only endemic mammalian species in the islands, however, ARs-sensitivity of fruit bats has been unclear. For the assessment, we performed pharmacokinetics analysis of ARs with Egyptian fruit bats (Rousettus aegyptiacus).
[Materials & Methods]
Animals; four female adult egyptian fruit (EF) bats and female Sprague Dawley (SD) rats (10 weeks old) were used in the study. Chemicals; we used two ARs (warfarin and diphacinone). Both of them were classified in the first generation ARs and have been commonly used in Japan. Methods; 4 mg/kg of warfarin sodium disloved in saline water was orally administrated to the EF bats and SD rats. Blood was taken from wing vein of EF bats and tail vein of SD rats. Prothrombin time (PT) was measured by CoaguCheck XS (Roche). Warfarin and its metabolites was extracted by liquid-liquid distribution with ether and their concentration was measured by HPLC-MS/MS (Shimadzu). After two month of warfarin administration, 4 mg/kg of diphacinone disolved in corn oil was also administrated to EF bats.
[Results and Discussion]
After warfarin administration, prolonged PT was observed in both EF bats and SD rats, however, EF bats recovered to normal value earlier than SD rats. EF bats showed higher clearance of warfarin than SD rats and produced higher amounts of warfarin-metabolites than SD rats. These results suggested EF bats were less sensitive to warfarin than SD rats due to their high warfarin excretion ability. On the other hand, PT prolonged earlier in EF bats after diphacinone exposure, although plasma concentration of diphacinone was significantly lower in EF bats than in SD rats. These results indicated fruit bats showed different sensitivity to warfarin and diphacinone, although they have same mode of action.
[Conclusion]
This study revealed Egyptian fruit bats were relatively tolerant to warfarin but susceptible to diphacinone compared to rats. Further study with Bonin fruit bats is required for safety usage of ARs.
