Hepatoprotective Effect of Metadoxine on Acetaminophen-induced Liver Toxicity in Mice

Background: Metadoxine (pyridoxine pyrrolidone carboxylate) is considered to be a beneficial agent for the treatment of experimental hepatotoxicity due to alcohol, CCl4, and bile duct ligation. Hence, the therapeutic effect of metadoxine and N-acetylcysteine (NAC) as reference drug was investigated in mice exposed to acute hepatotoxicity induced by a single oral toxic dose of acetaminophen (650 mg/kg). Materials and Methods: Metadoxine (200 and 400 mg/kg) and NAC (300 mg/kg) were given orally (p. o.), 2 h after acetaminophen administration. Serum aminotransferases, aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), total bilirubin, hepatic glutathione (GSH), and malondialdehyde (MDA) levels were determined for evaluating the extent of hepatotoxicity due to acetaminophen and its protection by metadoxine. Results: Findings indicated that metadoxine significantly reduced the level of serum ALT, AST, and ALP but not total bilirubin which increased by acetaminophen intoxication. Administration of metadoxine also attenuated oxidative stress by suppressing lipid peroxidation (MDA) and prevented the depletion of reduced GSH level which caused by acetaminophen toxicity. Besides, metadoxine ameliorated histopathological hepatic tissue injury induced by acetaminophen. Conclusion: In most parameters examined, the effect of metadoxine was comparable to NAC. Hence, metadoxine could be considered as a beneficial therapeutic candidate to protect against acute acetaminophen hepatotoxicity.