miRNA-324, a potential therapeutic target for paracetamol-induced liver injury
Paracetamol is one of the most widely used medications for relieving pain and fever. When taken in the therapeutic doses, paracetamol is predominantly metabolized in the liver via conjugation reaction by phase II drug metabolizing enzymes such as sulfotransferases and glucuronyl transferases, and is removed from the body without liver damage (1). However, when paracetamol is taken in excessive doses, it is bioactivated by phase I enzymes (e.g., CYP3A4 and CYP2E1) to generate a toxic intermediate N-acetyl-p-benzoquinone imine (NAPQI). Rapid generation of NAPQI can lead to the depletion of intrahepatic glutathione and result in hepatocyte death and liver injury (2). Thus, hepatotoxicity elicited by paracetamol overdose is the most common cause of poisoning-related deaths (3). In other studies, overdose of paracetamol accounted for the highest proportion of cases of acute liver failure in many developed countries, resulting in death or liver transplantation (4,5). Currently, N-acetylcysteine (NAC) is the mainstay strategy in treating hepatotoxicity following paracetamol overdose. However, oral and intravenous NAC treatment has limitations because of adverse effects (6,7). Thus, identifying new therapeutic targets would be of help for clinical remedy of paracetamol overdose-related liver injury.