CIPROFLOXACIN PREVENTS THE INHIBITORY EFFECTS OF ACUTE ETHANOL EXPOSURE ON HEPATIC REGENERATION IN THE RAT

To determine whether the inhibitory effects of ethanol on hepatic rege neration could be prevented by ciprofloxacin, a fluroquinolone antibio tic with gamma-aminobutyric acid (GABA(A)), receptor antagonist proper ties, adult, male Sprague-Dawley rats (n = 6.8/group) received intrape ritoneal injections of saline, putrescine (a hepatic growth promotor, 50 mg/kg), or ciprofloxacin (100 mg/kg), followed 1 hour later by gast ric gavage with saline or ethanol (5 g/kg). One hour post-gavage, all rats underwent a 70% partial hepatectomy (PHx). Hepatic regenerative a ctivity was documented 24 hours post-PHx by H-3-thymidine incorporatio n 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-gav aged/saline-treated rats (22.7 +/- 4.4 x 10(3) vs. 12.3 +/- 6.9 x 10(3 ) DPM/mg DNA, respectively, P < .001) but unaltered in putrescine-(18. 8 +/- 3.4 x 10(3) DPM/ mg DNA) and ciprofloxacin-treated (18.3 +/- 2.6 x 10(3) DPM/mg DNA) rats, Hepatic proliferating cell nuclear antigen staining supported these findings. Hepatic putrescine levels also corr elated with DNA synthesis data, being decreased in ethanol-gavaged/sal ine-treated rats (86 +/- 14 pmoles/mg tissue) compared with healthy co ntrols (120 +/- 12 pmoles/mg, P < .01), ethanol-gavaged/putrescine-tre ated (112 +/- 14 pmoles/mg, P < .05) and ethanol-gavaged/ciprofloxacin -treated (125 +/- 17 pmoles/mg, P < .05) rats. To determine whether th ese effects resulted hom GABAA receptor-mediated changes in liver memb rane potentials, intracellular membrane potentials were recorded befor e and 1 hour after PHx in healthy control, ethanol-gavaged/saline-trea ted and ethanol-gavaged/cipronoxacin-treated rats. In these studies, c iprofloxacin prevented ethanol-induced depolarization of the liver (ch ange in membrane potential of healthy controls, ethanol-gavaged/saline -treated, and ethanol-gavaged/cipronoxacin treated rats were -9 +/- 1, -15 +/- 2, and -3 +/- 1 mV, respectively). In conclusion, the results of this study indicate that the inhibitory effects of acute ethanol e xposure on hepatic regenerative activity in rats can be prevented by e xogenous ciprofloxacin.