PROTECTIVE EFFECTS OF MELATONIN AGAINST IDIOSYNCRATIC LIVER INJURY IN RATS CHALLENGED WITH CHLORPROMAZINE AND LIPOPOLYSACCHARIDE
Journal Title: International Research Journal of Pharmacy (IRJP) - Year 2011, Vol 2, Issue 3
Abstract
The episode of inflammation during drug treatment predispose animals to tissue injury, raising the possibility that presence or absence of inflammation is an important susceptibility factor for drug toxicity in human , and this phenomenon is hypothesized to be related to idiosyncratic drug reactions. The present study was designed to investigate the possible protective effect of orally administered melatonin against hepatic injury in rats concurrently treated with chlorpromazine (CPZ) and lipopolysaccharides (LPS). The protective effect of melatonin was studied through treatment of rats with single oral dose (10mg/kg), given seven days before and during the day of exposure to both CPZ and LPS. The animals were sacrificed 24 hrs post-challenge with LPS. Hepatic necrosis and cholestasis were assessed by measuring the activities of serum liver enzymes ALT, AST and ALP; in addition, total and direct bilirubin along with evaluation of histological alteration in hepatic tissue. The oxidative stress markers were assessed by measuring the levels of MDA and GSH in hepatic tissue homogenate. Analysis of data showed that melatonin supplementation attenuated markers of oxidative stress by reducing the levels of MDA and restoring GSH levels; melatonin also improved the observed biochemical and histological changes associated with exposure to CPZ and LPS. In conclusion, orally administered melatonin at pharmacological doses have promising protective effects against drug-induced idiosyncratic liver injury that may be of value in clinical practice.
Authors and Affiliations
Amal Sulaiman
Keywords
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