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.
Highlights
Tramadol (TD) is a centrally acting opioid analgesic which is mainly used for the treatment of moderate to severe pain.[1]
The present study investigated the protective effects of melatonin (MT) and nacetylcysteine (NAC) on TD-induced hepatotoxicity in albino rats
Liver is a key organ actively involved in numerous metabolic and detoxifying functions
Summary
Tramadol (TD) is a centrally acting opioid analgesic which is mainly used for the treatment of moderate to severe pain.[1] Its efficiency and potency ranges between weak opioids and morphine.[2] Clinically, hepatotoxity marked by cholelithiasis, cholecystitis, and abnormal liver function tests could occur in more than 1% of patients administered with TD.[3] due to its opiate-like and analgesic effects,[4] TD abuse, dependence as well as acute overdose have led to reported cases of hepatotoxicity and even death in humans.[5,6,7,8] Studies in animals have reported hepatotoxicity characterized by altered levels of liver function biomarkers[9,10] and histological damage.[11,12,13] In addition, oxidative stress could be involved in TD-induced hepatotoxicity due to decrease in antioxidant defence and lipid peroxidation observed in treated animals.[14]
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