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. Because alcoholic beverages contain appreciable amounts of GABA, we documented whether the inhibitor effects of alcohol on the liver are derived 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 then sacrificed and hepatic regenerative activity was documented by 3H-thymidine incorporation into hepatic DNA. Results: DNA synthesis was significantly inhibited by ethanol (−37%, p<0.005) and GABA (−19%, p<0.05). Maximum inhibition was achieved with the combination of ethanol plus GABA (−52%, p<0.001). To determine whether the additive effects of ethanol plus GABA were mediated by ethanol-induced enhancement of hepatic GABA, receptor activity, additional rats (n=6/group) receiving the combination of ethanol plus GABA were pre-treated with a single injection of either ciprofloxacin (50 mg/kg), a GABAA receptor antagonist, or an equal volume of saline. In these experiments, ciprofloxacin pre-treatment prevented the inhibitory effects of the ethanol plus GABA combination. Conclusions: The results of this study indicate that the 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.