To determine whether the inhibitory effects of ethanol on hepatic regeneration could be prevented by ciprofloxacin, a fluroquinolone antibiotic with gammaaminobutyric acid (GABAJ, receptor antagonist properties, adult, male Sprague-Dawley rats (n = 6-Wgroup) received intraperitoneal injections of saline, putrescine (a hepatic growth promotor, 50 mgkg), or ciprofloxacin (100 mgkg), followed 1 hour later by gastric gavage with saline or ethanol (5 gkg). One hour post-gavage, all rats underwent a 70% partial hepatectomy (PHx). Hepatic regenerative activity was documented 24 hours post-PHx by 3H-thymidine incorporation into hepatic DNA (DNA synthesis), proliferating cell nuclear antigen staining, and hepatic tissue putrescine levels. Compared with healthy controls, DNA synthesis rates were significantly lower in ethanol-gavagedsaline-treated rats (22.7 +-4.4
x lo3 vs. 12.3 2 6.9 x lo3 DPM/mg DNA, respectively, P < .001) but unaltered in putrescine-(18.8 2 3.4 X lo3 DPW mg DNA) and ciprofloxacin-treated (18.3 2 2.6 x lo3
DPWmg DNA) rats. Hepatic proliferating cell nuclear antigen staining supported these findings. Hepatic putrescine levels also correlated with DNA synthesis data, being decreased in ethanol-gavagedlsalinene-treated rats (86 ? 14 pmoledmg tissue) compared with healthy controls (120 t 12 pmoles/mg, P < .Ol), ethanol-gavagedlputrescine-treated (112 2 14 pmoledmg, P < .05) and ethanol-gavagedciprofloxacin-treated (125 ? 17 pmoledmg, P < .05) rats. To determine whether these effects resulted from GABAA receptor-mediated changes in liver membrane potentials, intracellular membrane potentials were recorded before and 1 hour after PHx in healthy control, ethanol-gavagedsaline-treated and ethanol-gavagedciprofloxacin-treated rats. In these studies, ciprofloxacin prevented ethanol-induced depolarization of the liver (change in membrane potential of healthy controls, ethanol-gavagedsaline-treated, and Abbreviations: GABA, y-aminobutyric acid; PHx, partial hepatectomy; PD, membrane potential.