Paracetamol, also known as acetaminophen, is a widely used over-the-counter analgesic pain reliever and antipyretic fever reducer . The liver plays a crucial role in the metabolism of paracetamol. The primary metabolic pathway for paracetamol involves three main enzymes: UDP-glucuronosyltransferase UGT , sulfotransferase SULT , and cytochrome P450 CYP450 .1. Glucuronidation: The majority of paracetamol about 50-70% is metabolized by UGT enzymes, mainly UGT1A1 and UGT1A6, to form paracetamol glucuronide. This is a non-toxic metabolite that is easily excreted in the urine.2. Sulfation: Approximately 25-35% of paracetamol is metabolized by SULT enzymes, primarily SULT1A1, to form paracetamol sulfate. This is another non-toxic metabolite that is excreted in the urine.3. Oxidation: A small fraction of paracetamol about 5-10% is metabolized by the CYP450 enzyme system, mainly CYP2E1, to form a highly reactive and toxic metabolite called N-acetyl-p-benzoquinone imine NAPQI . Under normal circumstances, NAPQI is rapidly detoxified by conjugation with glutathione GSH , a natural antioxidant present in the liver, to form non-toxic cysteine and mercapturic acid conjugates, which are then excreted in the urine.However, when paracetamol is taken in excessive amounts or when the liver's glutathione reserves are depleted, the accumulation of NAPQI can lead to hepatotoxicity liver damage . NAPQI can bind to cellular proteins, causing oxidative stress, mitochondrial dysfunction, and eventually, cell death. This can result in acute liver failure, which can be life-threatening.To minimize the risk of paracetamol-induced hepatotoxicity, it is essential to follow the recommended dosage guidelines and avoid consuming substances that can induce CYP2E1 activity e.g., alcohol or deplete glutathione levels e.g., certain medications or nutritional deficiencies . In cases of paracetamol overdose, the administration of N-acetylcysteine NAC can help replenish glutathione levels and prevent liver damage.