Abstract

Abstract Hepatotoxicity, a critical adverse effect observed with various pharmaceuticals, poses significant challenges in drug development and clinical practice. This integrative review explores the diverse mechanisms through which novel pharmaceuticals induce liver toxicity. Key mechanisms include direct hepatocyte injury via oxidative stress, mitochondrial dysfunction, and covalent binding; immune-mediated responses such as allergic and autoimmune-like reactions; and cholestasis resulting from BSEP inhibition and canalicular damage. The review also highlights the role of molecular pathways, including cytochrome P450 enzymes, nuclear receptors, and inflammatory cytokines, in mediating hepatotoxicity. Understanding these mechanisms is crucial for developing predictive biomarkers, improving preclinical testing, and enhancing risk stratification in clinical settings. The insights provided aim to support safer drug development and more effective management of drug-induced liver injury