Ciprofloxacin prevents the inhibitory effects of acute ethanol exposure on hepatic regeneration in the rat

Abstract

To determine whether the inhibitory effects of ethanol on hepatic regeneration could be prevented by ciprofloxacin, a fluroquinolone antibiotic with gammaaminobutyric acid (GABA A), receptor antagonist properties, adult, male Sprague-Dawley rats (n = 6–8/group) received intraperitoneal injections of saline, putrescine (a hepatic growth promotor, 50 mg/kg), or ciprofloxacin (100 mg/kg), followed 1 hour later by gastric gavage with saline or ethanol (5 g/kg). One hour post-gavage, all rats underwent a 70% partial hepatectomy (PHx). Hepatic regenerative activity was documented 24 hours postPHx 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-gavaged/saline-treated rats (22.7 ± 4.4 × 10 3 vs. 12.3 ± 6.9 × 10 9 DPM/mg DNA, respectively, P < .001) but unaltered in putrescine-(18.8 ± 3.4 × 10 3 DPM/ mg DNA) and ciprofloxacin-treated (18.3 ± 2.6 × 10 3 DPM/mg DNA) rats. Hepatic proliferating cell nuclear antigen staining supported these findings. Hepatic putrescine levels also correlated with DNA synthesis data, being decreased in ethanol-gavaged/saline-treated rats (86 ± 14 pmoles/mg tissue) compared with healthy controls (120 ± 12 pmoles/mg, P < .01), ethanol-gavaged/putrescine-treated (112 ± 14 pmoles/mg, P < .05) and ethanol-gavaged/ciprofloxacin-treated (125 ± 17 pmoles/mg, P < .05) rats. To determine whether these effects resulted from GABA A receptor-mediated changes in liver membrane potentials, intracellular membrane potentials were recorded before and 1 hour after PHx in healthy control, ethanol-gavaged/saline-treated and ethanol-gavaged/ciprofloxacin-treated rats. In these studies, ciprofloxacin prevented ethanol-induced depolarization of the liver (change in membrane potential of healthy controls, ethanol-gavaged/saline-treated, and ethanol-gavaged/ciprofloxacin-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 exposure on hepatic regenerative activity in rats can be prevented by exogenous ciprofloxacin.