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The beneficial effects of ciprofloxacin on survival and hepatic regenerative activity in a rat model of fulminant hepatic failure
Author(s) -
Kaita Kelly D.,
Assy Nimar,
Gauthier Tony,
Zhang Manna,
Meyers Adrienne F.,
Minuk Gerald Y.
Publication year - 1998
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.510270230
Subject(s) - intraperitoneal injection , norfloxacin , pharmacology , fulminant hepatic failure , medicine , saline , cirrhosis , ciprofloxacin , transplantation , endocrinology , biology , antibiotics , liver transplantation , biochemistry
Recently, we reported that ciprofloxacin, an antimicrobial agent with γ‐aminobutyric acid (GABA A ) receptor antagonist properties, significantly increases hepatic regenerative activity in animal models of alcohol‐induced liver disease and cirrhosis. In the present study, we documented the effects of ciprofloxacin on survival and hepatic regeneration in a d ‐galactosamine ( d ‐gal)‐induced model of acute hepatic injury in rats. One hundred nineteen adult, male Sprague‐Dawley rats (n = 19‐20/group) were treated with intraperitoneal d ‐gal (total dose: 2.5 g/kg), followed by gastric gavage with either saline, ciprofloxacin (10, 50, or 100 mg/kg), norfloxacin (250 mg/kg), or intraperitoneal putrescine (300 μmol/kg), a potent hepatic growth promoter. Mortality rates were then documented over a 4‐day period. An additional 45 rats (n = 15/group) received a sublethal dose of d ‐gal (1.0 g/kg), followed by gastric gavage with either saline or ciprofloxacin (100 mg/kg), or intraperitoneal putrescine (300 μmol/kg). In these rats, hepatic regenerative activity was documented at 12, 24, and 60 hours post– d ‐gal by 3 H‐thymidine incorporation into hepatic DNA and proliferating cell nuclear antigen (PCNA) staining. In the survival study, a dose‐response effect of ciprofloxacin on survival was observed (ciprofloxacin: 10 mg/kg, 10%; 50 mg/kg, 26%; and 100 mg/kg, 35%) with the results in the 100‐mg/kg–treated group being significant when compared with the 5% survival rate in saline‐treated controls ( P < .05). Survival figures in the norfloxacin‐ and putrescine‐treated groups were not significantly improved (15% and 25%, respectively). In the regeneration study, compared with the d ‐gal + saline‐treated control group, DNA synthesis rates at 60 hours were increased in the d ‐gal + ciprofloxacin and d ‐gal + putrescine groups (10.2 ± 3.3 vs. 18.2 ± 5.1 and 18.8 ± 6.8 × 10 3 dpm/mg DNA respectively; P < .05). The results of PCNA staining also supported enhanced hepatic regeneration in the ciprofloxacin‐treated group at 60 hours (saline, 13.4 ± 3.7; ciprofloxacin, 47.4 ± 7.3; and putrescine, 8.4% ± 2.8% hepatocytes staining positive). Ciprofloxacin at a dose of 100 mg/kg significantly improves survival and hepatic regenerative activity in this animal model of acute hepatic injury.