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Therefore, the present study investigated whether exogenous H<jats:sub>2<\/jats:sub>S protects against arecoline\u2010induced neurotoxicity and further explore the underlying mechanisms focusing on leptin\/leptin receptor signaling pathway. The cell viability was measured by CCK\u20108 kit. The apoptosis were detected by Hoechst 33258 and Annexin V\/PI (propidium iodide) staining. The protein expressions were determined by Western blot analysis. Our results demonstrated that NaHS, an exogenous H<jats:sub>2<\/jats:sub>S donor, significantly increases the cell viability, decreases apoptosis ratio, and reduces caspase\u20103 activity as well as Bax\/Bcl\u20102 ratio in PC12 cells exposed to arecoline, indicating the protection of H<jats:sub>2<\/jats:sub>S against arecoline\u2010induced cytotoxicity and apoptosis. Also, NaHS attenuated arecoline\u2010induced endoplasmic reticulum (ER) stress, as evidenced by the decreases in the expressions of glucose\u2010regulated protein 78 (GRP78), C\/EBP homologous protein (CHOP), and Cleaved caspase\u201012. Meanwhile, NaHS promoted leptin\/leptin receptor signaling pathway in arecoline\u2010exposed PC12 cells, as illustrated by upregulations of leptin and leptin receptor expressions. Furthermore, leptin tA, an antagonist of leptin receptor, obviously abolished the inhibitory effects of NaHS on arecoline\u2010induced cytotoxicity, apoptosis, and ER stress in arecoline\u2010exposed PC12 cells. Taken together, these results suggested that H<jats:sub>2<\/jats:sub>S prevents arecoline\u2010induced neurotoxicity via enhancing the leptin\/leptin receptor signaling pathway.<\/jats:p>","DOI":"10.1002\/cbin.11850","type":"journal-article","created":{"date-parts":[[2022,7,12]],"date-time":"2022-07-12T11:11:44Z","timestamp":1657624304000},"page":"1355-1366","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Hydrogen sulfide prevents arecoline\u2010induced neurotoxicity via promoting leptin\/leptin receptor signaling pathway"],"prefix":"10.1002","volume":"46","author":[{"given":"Xiang","family":"Cheng","sequence":"first","affiliation":[{"name":"The First Affiliated Hospital, Department of Clinical Laboratory, Hengyang Medical College University of South China  Hengyang Hunan P.R. 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