THE EFFECTS OF ETHANOL AND GAMMA-AMINOBUTYRIC-ACID ALONE AND IN COMBINATION ON HEPATIC REGENERATIVE ACTIVITY IN THE RAT

Background/Aims: Both ethanol and gamma aminobutyric acid (GABA) have been reported to inhibit hepatic regenerative activity in the rat. Bec ause alcoholic beverages contain appreciable amounts of GABA, we docum ented whether the inhibitory effects of alcohol on the liver are deriv ed from ethanol alone or the combination of ethanol plus GABA. Methods : Adult male Sprague-Dawley rats (n=6/group) were treated with either ethanol (3 g/kg), GABA (500 mg/kg) or ethanol plus GABA (3 kg and 500 mg/kg, respectively), beginning 1 h prior to a 70% partial hepatectomy and continued every 4 h thereafter for a total of 24 h, Rats were the n sacrificed and hepatic regenerative activity was documented by H-3-t hymidine incorporation into hepatic DNA. Results: DNA synthesis was si gnificantly inhibited by ethanol (-37%, p<0.005) and GABA (-19%, p<0.0 5). Maximum inhibition was achieved with the combination of ethanol pl us GABA (-52%, p<0.001), To determine whether the additive effects of ethanol plus GABA were mediated by ethanol-induced enhancement of hepa tic GABA(A) receptor activity, additional rats (n=6/group) receiving t he combination of ethanol plus GABA were pre-treated with a single inj ection of either ciprofloxacin (50 mg/kg), a GABA(A) receptor antagoni st, or an equal volume of saline. In these experiments, ciprofloxacin pre-treatment prevented the inhibitory effects of the ethanol plus GAB A combination. Conclusions: The results of this study indicate that th e combination of ethanol plus GABA has a greater inhibitory effect on hepatic DNA synthesis following partial hepatectomy than ethanol alone . The clinical implication of this finding is that, when standardized for ethanol content, not all alcoholic beverages would be expected to have the same inhibitory effect on hepatic regeneration.