Hepatoprotective effect of cimetidine and ciprofloxacin on paracetamol-induced hepatotoxicity in male albino rats
الملخص
Paracetamol induced hepatotoxicity results from hepatic enzymatic oxidation of paracetamol to a toxic, electrophilic intermediate. Cimetidine and ciprofloxacin has been shown to inhibit the hepatic oxidation of a number of drugs.The present study was designed to investigate the hepatoprotective effect of cimetidine and ciprofloxacin against paracetamol induced hepatotoxicity in male albino rats. The hepatotoxicity was induced by the intraperitoneal(i.p) administration of paracetamol at a dose of 500 mg/kg in male albino rats. Biochemical analysis of plasma levels of ALT, AST, ALP, LDH and bilirubin were determined as measures of liver function. Our results showed that levels of liver enzymes ALT, AST, ALP, LDH and bilirubin level were significantly enhanced by administration of paracetamol indicating a considerable hepatocellular injury. However, the co-treatment with 150 mg/kg cimetidine i.p 2 hours prior to paracetamol injection revealed a significant attenuation of serum ALT, AST, ALP, LDH and bilirubin levels. On the other hand, the co-treatment with 25 mg/kg ciprofloxacin i.p 2 hours before paracetamol treatment didn't show any protective effect on liver function. The present results clearly demonstrate the marked protective effect of cimetidine against paracetamol induced hepatotoxicity in rats, effect which could have been mediated via its inhibition of the CYP450 system responsible for the metabolism of paracetamol. Therefore, the production of the toxic metabolite (NAPQI) will be decreased. Further studies are required, by measuring the CYP450 isoforms activities in human liver microsomes to confirm this protective effect.
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