Diazinon-induced oxidative stress and organ toxicity in rodent models: a narrative review of mechanistic pathways, biomarkers and antioxidant interventions.

Diazinon (DZN) is a widely used organophosphorus insecticide whose toxicity has traditionally been attributed to acetylcholinesterase inhibition after metabolic activation to diazoxon. However, a growing body of rodent evidence indicates that this mechanism alone does not adequately explain the breadth and persistence of DZN-induced organ injury, particularly under subacute and subchronic exposure conditions. This narrative review synthesizes current evidence on the toxicokinetic, mechanistic and organ-specific basis of DZN-induced oxidative stress in rodent models, with emphasis on biomarker behaviour and the protective effects of antioxidant and pharmacological interventions. Relevant studies were identified from PubMed/MEDLINE, Scopus and Web of Science up to December 2025, with inclusion limited to in vivo rodent and rodent-derived ex vivo studies that assessed oxidative or nitrosative stress endpoints alongside organ injury or functional outcomes. Across the reviewed literature, DZN consistently increased reactive oxygen and nitrogen species, lipid peroxidation and protein oxidation, while depleting glutathione and disrupting antioxidant defenses such as superoxide dismutase, catalase and glutathione peroxidase. These redox disturbances were closely associated with inflammatory activation, mitochondrial dysfunction, and oxidative DNA damage and tissue injury in the liver, kidney, cardiovascular system, brain, reproductive organs, pancreas, adipose tissue and blood. Time-course and correlation data further indicate that oxidative stress develops rapidly, may precede or coincide with peak cholinesterase inhibition, and often persists beyond the overt cholinergic phase, supporting a partially dissociated but mechanistically intertwined oxidative axis. Intervention studies show that antioxidants, phytochemicals and selected pharmacological agents can attenuate DZN-induced redox imbalance and ameliorate biochemical and histopathological damage, although protection is typically incomplete. Overall, the evidence positions oxidative stress as a central cross-organ mechanism of DZN toxicity rather than a secondary by-product of cholinergic injury. A more standardized and translationally integrated research framework is now needed to refine biomarker selection, improve hazard characterisation and guide the development of adjunctive strategies for organophosphate-related toxicity.