Melatonin inhibits atrazine-induced mitochondrial impairment in cerebellum of mice: Modulation of cGAS-STING-NLRP3 axis-dependent cell pyroptosis

• Published in: The Science of the total environment 2024-02, Vol.912, p.168924-168924, Article 168924
• Main Authors: Liu, Lin, Li, Mu-Zi, Yao, Ming-Hui, Yang, Tian-Ning, Tang, Yi-Xi, Li, Jin-Long
• Format: Article
• Language: English
• Subjects: Atrazine; Cerebellum injury; cGAS-STING axis; Inflammation; Melatonin
• ISSN: 0048-9697; 1879-1026
• DOI: 10.1016/j.scitotenv.2023.168924

The global prevalence of Neurological disorders has increased alarmingly in response to environmental and lifestyle changes. Atrazine (ATZ) is a difficult to degrade soil and water pollutant with well-known neurotoxicity. Melatonin (MT), an antioxidant with chemoprotective properties, has a potential therapeutic effect on cerebellar damage caused by ATZ exposure. The aim of this study was to explore the effects and underlying mechanisms of MT on the cerebellar inflammatory response and pyroptosis induced by ATZ exposure. In this study, C57BL/6J mice were treated with ATZ (170 mg/kg BW/day) and MT (5 mg/kg BW/day) for 28 days. Our results revealed that MT alleviated the histopathological changes, ultrastructural damage, oxidative stress and decrease of mitochondrial membrane potential (ΔΨm) in the cerebellum induced by ATZ exposure. ATZ exposure damaged the mitochondria leading to release of mitochondrial DNA (mtDNA) to the cytoplasm, MT activated the cyclic GMP-AMP synthetase interferon gene stimulator (cGAS-STING) axis to alleviate inflammation and pyroptosis caused by ATZ exposure. In general, our study provided new evidence that the cGAS-STING-NLRP3 axis plays an important role in the treatment of ATZ-induced cerebellar injury by MT. [Display omitted] •MT inhibits cerebellar damage caused by ATZ exposure.•MT can significantly improve the disorder of antioxidant response caused by ATZ exposure.•MT inhibits the cerebellar cGAS-STING-related pathway response induced by ATZ exposure.•MT inhibits ATZ-induced Caspase-1/NLRP3-dependent pyroptosis and inflammation.