DRUG-INDUCED LIVER TOXICITY: MECHANISMS AND THERAPEUTIC TARGETS

Abstract

Drug-induced liver injury (DILI) remains a critical challenge in clinical pharmacology, posing significant health risks and limiting the therapeutic potential of numerous drugs. This review explores the underlying mechanisms of DILI and highlights emerging therapeutic strategies aimed at mitigating hepatotoxicity. The pathogenesis of DILI involves intricate interactions between drugs and hepatic cellular structures, leading to oxidative stress, mitochondrial dysfunction, immune-mediated damage, and apoptotic pathways. Key molecular mediators, including cytochrome P450 enzymes, reactive oxygen species (ROS), and pro-inflammatory cytokines, are critically examined. Additionally, the limitations of current diagnostic biomarkers in predicting DILI are discussed. Emerging therapeutic approaches focus on modulating oxidative stress, enhancing mitochondrial protection, and regulating immune responses. Potential targets such as nuclear factor erythroid 2-related factor 2 (Nrf2), peroxisome proliferator-activated receptors (PPARs), and microRNAs (miRNAs) offer promising avenues for reducing hepatocellular injury. Furthermore, the role of personalized medicine and genetic predisposition in DILI susceptibility is explored, emphasizing the need for tailored interventions. This review underscores the importance of advancing research to develop reliable biomarkers and innovative therapeutics, ultimately improving patient safety and drug efficacy.

DOI - https://doi.org/10.65525/SVUP.9788198800473.2025.199-208