Diquat exacerbates oxidative stress and neuroinflammation by blocking the autophagic flux of microglia in the hippocampus

Diquat (DQ) is a widely utilized nonselective herbicide that is primarily used to control a wide range of weeds and crop residues. It also has significant environmental implications. DQ exposure can cause severe damage to the central nervous system (CNS), a critical symptom of acute poisoning that endangers patients. Despite its severity, the underlying mechanisms of DQ-induced toxic encephalopathy remain unclear, hindering the development of precise treatments. Our research demonstrated that acute DQ exposure in mice significantly increases oxidative stress and triggers neuroinflammation in the hippocampus. Furthermore, in vitro findings indicate that the detrimental effects of DQ are mediated by its disruption of autophagic processes, leading to exacerbated neural damage. DQ initially promotes autophagy in BV2 microglia for self-protection against oxidative stress and inflammation. However, this process is subsequently blocked, intensifying neural damage. Crucially, our results show that the activation of autophagy can reverse these adverse effects. This study not only sheds light on the intricate mechanisms of DQ neurotoxicity but also provides potential therapeutic targets for mitigating DQ-induced toxic encephalopathy. [Display omitted] •DQ increases oxidative stress and triggers neuroinflammation in mouse hippocampus.•DQ induces autophagy in microglia, with normal initiation but impaired flux in later stages.•DQ disrupts autophagy, blocking its protective role in microglia and worsening neural damage.•Autophagy activation can attenuate DQ-induced oxidative stress and inflammatory response.