Abstract

The liver and kidney are critical organs responsible for metabolism, detoxification, and excretion, making them 
highly susceptible to toxic injury. Hepatotoxicity and nephrotoxicity arise from diverse insults, including 
xenobiotics, drugs, environmental chemicals, and metabolic disturbances. Recent insights highlight the pivotal role 
of immunomodulation in driving organ injury, with oxidative stress serving as a unifying mechanism that bridges 
immune activation and cellular dysfunction. Excessive generation of reactive oxygen and nitrogen species disrupts 
mitochondrial homeostasis, induces DNA and protein damage, and amplifies lipid peroxidation, thereby sensitizing 
hepatic and renal cells to immune-mediated injury. In parallel, immune pathways-such as Toll-like receptor 
signaling, NLRP3 inflammasome activation, T-cell polarization, and macrophage reprogramming-sustain 
inflammatory responses that accelerate fibrosis and organ dysfunction. This review synthesizes current evidence on 
the immunological and redox-dependent drivers of hepatotoxicity and nephrotoxicity, emphasizing shared 
molecular pathways, organ crosstalk, and the therapeutic potential of antioxidant and immunomodulatory 
interventions. 
Keywords: hepatotoxicity, nephrotoxicity, immunomodulation, oxidative stress, inflammation