PARACETAMOL-INDUCED HEPATOTOXICITY: A COMPREHENSIVE REVIEW OF MECHANISMS, BIOMARKERS, AND THERAPEUTIC ADVANCES

Astikta Ashok Bhondave*, Aditi Rajaendra Waghmare, Dr. Hemant V. Kamble and S. R. Ghodake

ABSTRACT

Background: Paracetamol (acetaminophen) is one of the most frequently used drugs for relieving pain and fever. Although safe at therapeutic doses, an overdose can lead to serious liver damage and is a major contributor to drug-induced liver injury worldwide. Objective: This review presents an overview of paracetamol-induced liver toxicity, exploring mechanisms of injury, risk factors, diagnostic approaches, and both conventional and emerging treatments including natural hepatoprotective agents. Methods: Peer-reviewed studies were examined to summarize current understanding of paracetamol pharmacokinetics, liver toxicity mechanisms, diagnostic markers, and novel therapeutic strategies. Results: The primary toxic effect results from the formation of a reactive metabolite (NAPQI), which depletes glutathione and causes oxidative stress, mitochondrial dysfunction, and hepatocyte death. Factors like chronic alcohol intake, malnutrition, and genetics can worsen toxicity. While N-acetylcysteine remains the standard antidote, new therapies involving antioxidants and phytochemicals have shown promise in experimental studies. Conclusion: Paracetamol-induced hepatotoxicity is a preventable but potentially life-threatening condition. Early intervention is crucial, and recent advances in biomarkers and therapeutic agents offer hope for better management and outcomes.

Keywords: Paracetamol, Acetaminophen, Hepatotoxicity, N-acetylcysteine, Oxidative stress, Glutathione, Mitochondrial dysfunction, Biomarkers, Necroptosis, Liver injury, Antioxidants