Diquat-induced organ toxicity: a focus on regulated cell death pathways and mitochondrial dysfunction

Diquat (1,1'-ethylene-2,2'-bipyridyl, DQ) is a herbicide widely used for weed control in both agricultural and non-cultivated areas. Although its acute toxicity is lower than that of paraquat, its high-water solubility and stability in acidic and neutral environments contribute to its prolonged environmental persistence. As DQ gradually replaces paraquat in agricultural practice, the incidence of DQ poisoning has increased significantly. DQ poisoning typically results from accidental ingestion, suicidal intake, or improper agricultural handling. To date, no specific antidote is available, and the high mortality associated with DQ poisoning presents a critical challenge for clinical management. Accumulating evidence indicates that the toxicity of DQ is primarily attributed to its capacity to generate reactive oxygen species (ROS), leading to oxidative stress and subsequent oxidative damage to lipids, proteins, and DNA, ultimately resulting in multi-organ dysfunction, with the kidneys and intestines being the primary target organs. The pathogenesis of DQ poisoning involves multiple factors, including oxidative stress imbalance, regulated cell death, mitochondrial dysfunction, and disturbances in energy metabolism. This review systematically examines the physicochemical properties, metabolic characteristics, biodistribution, and target organ toxicity of DQ, with a particular focus on the interplay between excessive ROS production and mitochondrial dysfunction in the context of oxidative stress. Furthermore, we provide an in-depth discussion on the roles of regulated cell death-including pyroptosis, ferroptosis, and mitophagy-and metabolic dysregulation in DQ-induced toxicity. In addition, this review summarizes the classical signaling pathways involved in organ dysfunction, current therapeutic strategies, and potential intervention targets, thereby offering a theoretical framework and future research directions for the management of DQ poisoning.