Antioxidant properties and Glutathione S-transferases inhibitory activity of Alchornea cordifolia leaf extract in Acetaminophen toxicity

Paracetamol (acetaminophen, PCM) is a widely used over-the-counter analgesic and antipyretic drug. Intake of a large dose of PCM may result in severe hepatic necrosis. Oxidative stress is mediated by oxidative capacities of the PCM metabolite (N-acetyl-para-benzo quinoneimine, NAPQI), which covalently binds to proteins and other macromolecules to cause cellular damage. At low doses, NAPQI is considered as the main cause of PCM toxicity.   This work therefore was designed to evaluate the antioxidant potential of Alchornea cordifolia and to study the effect of its ethanol extract pretreatment (100-500mg/Kg) for two weeks before paracetamol intoxication (2g/Kg) on glutathione S-transferases activity. The antioxidative property revealed total phenol level of 0.22mg/ml and reducing power 0.062mg/ml which was higher than vitamin E reducing value of 0.042 mg/ml. Paracetamol toxicity produced a significant decrease in the hepatic levels of glutathione S-transferases when compared with the control. Alchornea cordifolia significantly reduced the level of hepatic glutathione S- transferase but it however , produced a dose dependent significant increase in the levels of glutathione S-transferases in the presence of the toxicant.   The results suggest that the Alchornea cordifolia is a potent antioxidant since the detoxification of paracetamol can be mediated by glutathione S-transferase (GST) catalyzed conjugation with glutathione (GSH) in the liver. The plant extract can ameliorate the effect of PCM intoxication. The increased hepatic glutathione S-transferases (GSTs) levels induced by the extract treatment can, therefore, reduce the acute paracetamol toxicity.