ALCOHOL HEPATIC TOXICITY IN RAT - EVIDENCE OF THE UTILITY OF GASTRIC ETHANOL-METABOLISM

Since a fraction of ingested ethanol (EtOH) is metabolized by gastric mucosa, different amounts of alcohol should reach the liver, when the same dose is administered by oral or intravenous route. Accordingly, w e demonstrated that the hepatic depletion of glutathione induced by Et OH is lower when it is administered orally rather than intraperitoneal ly (i.p.). In the present study we investigated, after EtOH load, the time-course of common serum liver damage tests and of alpha-glutathion e-S-transferase (alpha GST) levels as a new indicator of hepatocellula r injury in rats. The tests were also performed in Cimetidine-treated rats. Oral EtOH administration was followed by a less pronounced decre ase and by a quicker recovery of hepatic glutathione than after i.p. r oute. After oral EtOH load, Cimetidine, a potent inhibitor of gastric alcohol-dehydrogenase, produced a decrease of hepatic glutathione sign ificantly (P < 0.005) more pronounced than in controls. Serum alpha GS T increased significantly (P < 0.05) 6 h after i.p. EtOH administratio n, whereas no modifications were found after oral EtOH load. Common li ver damage tests did not show any modification. In Cimetidine-treated rats, oral EtOH load was followed by an increase of serum alpha GST si milar to that after i.p. administration. This study demonstrates the b eneficial effects of gastric EtOH metabolism on the liver. The lack of gastric alcohol metabolism resulted not only in decreased content and delayed recovery of liver glutathione, but in potential hepatocellula r damage. (C) 1996 Elsevier Science Ireland Ltd.