Pharmacokinetics of the ethanol bioavailability in the regenerating rat liver induced by partial hepatectomy.
It is well known that a single ethanol administration is capable of inhibiting the two-thirds partial hepatectomy (PH)-induced liver regeneration (LR); nonetheless, it has not been elucidated how ethanol metabolism by the remnant liver is exerting the deleterious ethanol actions on LR. Indeed, pharmacokinetics analysis of ethanol elimination is lacking in rats subjected to PH, which might extend our understanding in the mechanisms that account for the ethanol-induced inhibition on LR after PH in the rat. Therefore, the present study is a pharmacokinetics analysis comparing intragastric and intraperitoneal administrations of ethanol to rats under PH, at several times after surgery (0 to 96 hr postsurgery). Our results show that PH rats had a much lower blood ethanol peak than sham-operated, when intragastrically administered during the first 4 hr after surgery that was transient and normalized at 6 hr post-PH. The area under the curve for blood ethanol was higher in PH animals, starting after 6 hr postsurgery and extended to the all replicative period, and returned within the control values thereafter. The quantity of ethanol absorbed after its intraperitoneal injection was essentially the same as the administered dose for all of the groups tested. Hence, ethanol bioavailability diminished due to an enhanced rate of the first-pass metabolism for ethanol in PH rats at the very early times post-PH. At later times of PH, ethanol bioavailability was practically normalized, and these effects were accompanied by a drastic increase in the liver capacity to metabolize ethanol, mainly at 48 to 96 hr after surgery, as calculated as ethanol elimination per gram of liver, as well as by total body weight. The very early changes in ethanol bioavailability in PH rats were not accounted for gastric ethanol retention in these animals. In conclusion, first-pass metabolism importantly participates in the modified ethanol bioavailability at very early times after PH, an event presumably attained to gastric catabolism of ethanol. However, the very enhanced metabolism of ethanol showed by the regenerating liver, particularly after the first 24 hr postsurgery, seems to be the main factor affecting ethanol pharmacokinetics in rats subjected to PH. The underlying mechanisms in this liver enhancement of ethanol oxidation by PH rats remains to be elucidated.
Morales-González
J A
JA
Departamento de Biología Celular, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, México City.
Gutiérrez-Salinas
J
J
Hernández-Muñoz
R
R
D000426:Alcohol Dehydrogenase / Q000502:physiology; D000818:Animals; D001682:Biological Availability; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D000431:Ethanol / Q000493:pharmacokinetics* / Q000633:toxicity; D006498:Hepatectomy; D008115:Liver Regeneration / Q000187:drug effects* / Q000502:physiology; D008297:Male; D010084:Oxidation-Reduction; D051381:Rats; D017208:Rats, Wistar
D000431:Ethanol; D000426:Alcohol Dehydrogenase