Publications

The liver is the primary site for xenobiotic metabolism and detoxification, rendering it particularly vulnerable to injury from drugs, environmental toxicants, dietary chemicals, and industrial pollutants. Hepatotoxicity triggers complex interactions between metabolic pathways and immune signaling networks, leading to immune dysregulation that can progress from acute hepatic injury to chronic inflammation and long-term liver diseases. Recent evidence shows that metabolic activation of xenobiotics generates reactive metabolites, oxidative stress, mitochondrial dysfunction, and endoplasmic reticulum stress, all of which initiate inflammatory responses mediated by Kupffer cells, hepatocytes, dendritic cells, and infiltrating immune cells. These events involve pattern recognition receptors, inflammasome activation, cytokine secretion, and modulation of adaptive immune responses. Persistent dysregulation of the hepatic immune environment drives fibrosis, steatohepatitis, metabolic derangements, and hepatocarcinogenesis. This review examines emerging mechanisms linking xenobiotic metabolism to immune activation, with emphasis on redox signaling, damage-associated molecular patterns, dysregulated cytokine networks, microbiome-derived metabolites, and genetic susceptibility factors. Understanding these interconnected pathways is essential for the development of targeted therapies, predictive biomarkers, and strategies for mitigating xenobiotic-induced chronic liver disease.