Melatonin and N- Acetylcysteine as Remedies for Tramadol-Induced Hepatotoxicity in Albino Rats

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.

Oxidative-antioxidative status and hepatic and renal factors following melatonin administration in castrated and intact dogs

“…Alkaline phosphatase (ALP) is markedly elevated in response to cholestasis. The hepatoprotective effects of melatonin, such as acetylsalicylic acid-induced liver damage in rats [11], rats fed with a high-fat ratio [12], hepatic necrosis in streptozotocin-induced diabetic rats [13], and tramadol-induced hepatotoxicity in albino rats [14], have been confirmed in experimental studies. Oxidative stress and inflammation induced during aging in the liver have been more marked in castrated than in the intact female rats.…”

The Effect of Selenium Nanoparticles on Tramadol Induced Hepatotoxicity in a Rat Model

“…Similar changes in liver enzymes have been recorded in previous experiments. [8,41] They attributed this impairment to leakage of the previously mentioned biomarkers into the plasma following an increased permeability of the hepatocyte cell membrane secondary to lipid peroxidation. [42] This is in line with the increased MDA level observed in the current study.…”

Melatonin and alpha lipoic acid restore electrolytes and kidney morphology of lopinavir/ritonavir-treated rats

“…MT is a multifunctional, universal and chain breaking antioxidant that forms reaction cascade against oxidants. Furthermore, it regulates a number of inflammatory reactions by up-regulating anti-inflammatory and inhibiting pro-inflammatory cytokines (32). ALA is a thiol containing antioxidant that terminates oxidative and nitrosative stress by scavenging and neutralizing ROS and RNS.…”