Abstract
Purpose: The therapeutic benefit derived from the clinical
use of tramadol (TD) has been characterized by hepatotoxicity due to misuse and
abuse. The implications of
drug-induced hepatotoxicity include socio-economic burden which makes the
search for remedy highly imperative. The present study investigated the
protective effects of melatonin (MT) and n-acetylcysteine (NAC) on TD-induced
hepatotoxicity in albino rats.
Methods: Forty five adult rats used for this study were divided into nine groups of five
rats each. The rats were pretreated with 10mg/kg/day of NAC, 10mg/kg/day of MT
and combined doses of NAC and MT prior to the administration of 15 mg/kg/day of
TD intraperitoneally for 7 days respectively. At the termination of drug
administration, rats were weighed, sacrificed, and serum was extracted and
evaluated for liver function parameters. The liver was harvested, weighed and
evaluated for oxidative stress indices and liver enzymes.
Results: Alanine
aminotransferase, alkaline phosphatase, aspartate aminotransferase, total
bilirubin, conjugated bilirubin, and malondialdehyde levels were significantly
(P<0.05) increased in rats administered with TD when compared to control.
Furthermore, glutathione, superoxide dismutase and catalase levels were
decreased significantly (P<0.05) in rats administered with TD when compared
to control. The Liver of TD-treated rats showed necrosis of
hepatocytes. However, the observed biochemical and liver histological
alterations in TD-treated rats were attenuated in NAC and MT pretreated rats.
Interestingly, pretreatment with combined doses of NAC and MT produced
significant (P<0.05) effects on all evaluated parameters in comparison to their
individual doses.
Conclusion: Based on the findings in this study, melatonin and n- acetylcysteine
could be used clinically as remedies for tramadol associated hepatotoxity.