Comparative analysis of glucuronidation of ethanol in treeshrews, rats and humans.

ABSTRACT

1. The treeshrews consume food-derived alcohol (ethanol) at a dose that would intoxicate humans, highlighting a marked difference in detoxification of ethanol between the animal species and humans. 2. In this study, we reported that the treeshrews and rats exhibited considerably high glucuronidation capacity for ethanol. Ethanol glucuronidation was 7.1-fold (for the liver microsomes) or 29.2-fold (for the intestine microsomes) more efficient in treeshrews than in humans. Similar to treeshrews, rats also showed a high efficiency in glucuronidating ethanol. 3. In the single-pass perfused intestinal model, significant amount of ethyl glucuronide (EtG) was excreted into the perfusate (for both treeshrews and rats) and bile (for rats). Biliary excretion of EtG was 8.8-13.4 times of intestinal excretion of EtG, suggesting that the liver played a determinant role in glucuronidation of ethanol. In vivo pharmacokinetics showed that EtG production was rapid in the animals with a Tmax value of ≤ 1.75 h. The excreted EtG into urine was 0.11-0.13% of dosed ethanol, a value increased by a 5.5- to 6.6-fold compared to that in humans. 4. This was the first report that the glucuronidation activity toward ethanol was much higher in treeshrews and rats than that in humans, revealing a marked species difference in ethanol glucuronidation.