Characterization of species differences in xenobiotic metabolism in non-experimental animals

Abstract

The ability to metabolize xenobiotics in organisms has a wide degree of variation among organisms. This is caused by differences in the pattern of xenobiotic bioaccumulation among organisms, which affects their tolerance. It has been reported in the veterinary field that glucuronidation (UGT) activity in cats, acetylation activity in dogs and sulfation (SULT) activity in pigs are sub-vital in these species, respectively, and require close attention when prescribing the medicine. On the other hand, information about species differences in xenobiotics metabolism remains insufficient, especially in non-experimental animals. In the present study, we tried to elucidate xenobiotic metabolism ability, especially in phase II UGT conjugation of various non-experimental animals, by using newly constructed in vivo, in vitro and genomic techniques. The results indicated that marine mammals (Steller sea lion, northern fur seal, and Caspian seal) showed UGT activity as low as that in cats, which was significantly lower than in rats and dogs. Furthermore, UGT1A6 pseudogenes were found in the Steller sea lion and Northern fur seal; all Otariidae species are thought to have the UGT1A6 pseudogene as well. Environmental pollutants and drugs conjugated by UGT are increasing dramatically in the modern world, and their dispersal into the environment can be of great consequence to Carnivora species, whose low xenobiotic glucuronidation capacity makes them highly sensitive to these compounds