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.
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