HEPATOTOXICITY: A COMPREHENSIVE REVIEW ON MECHANISMS, BIOMARKERS, AND THERAPEUTIC STRATEGIES

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

ABSTRACT

Hepatotoxicity, particularly drug-induced liver injury (DILI), represents a major challenge in pharmacology, toxicology, and clinical practice due to its unpredictable nature and potential severity. The liver's central role in detoxification makes it highly susceptible to various insults, including pharmaceuticals, herbal remedies, and industrial chemicals. This review provides an in-depth analysis of the molecular mechanisms of hepatotoxicity, such as oxidative stress, mitochondrial dysfunction, endoplasmic reticulum stress, immune activation, and bile acid dysregulation. Emerging biomarkers, including microRNA-122, HMGB1, and cytokeratin-18, offer mechanistic and predictive insights beyond traditional markers like ALT and AST.[1,2] We explore both in vitro and in vivo models used to study liver injury and highlight therapeutic strategies ranging from antidotes like N-acetylcysteine to phytochemicals such as silymarin and trigonelline.[3,4] Emphasis is placed on novel therapeutic approaches targeting mitochondrial protection, inflammation modulation, and apoptosis inhibition. Future directions include the development of human-relevant models, personalized medicine, and integration of omics-based diagnostics to enhance hepatotoxicity prediction and management.

Keywords: Hepatotoxicity, Drug-Induced Liver Injury (DILI), Oxidative Stress, Liver Biomarkers, Acetaminophen Toxicity, Experimental Models.