{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T00:43:59Z","timestamp":1789087439232,"version":"build-2803163510"},"reference-count":55,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T00:00:00Z","timestamp":1715558400000},"content-version":"vor","delay-in-days":12,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["2021YFC2700200"],"award-info":[{"award-number":["2021YFC2700200"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Pineal Research"],"published-print":{"date-parts":[[2024,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>10\u2010Hydroxycamptothecin (HCPT) is a widely used clinical anticancer drug but has a significant side effect profile. Melatonin has a beneficial impact on the chemotherapy of different cancer cells and reproductive processes, but the effect and underlying molecular mechanism of melatonin's involvement in the HCPT\u2010induced side effects in cells, especially in the testicular cells, are poorly understood. In this study, we found that melatonin therapy significantly restored HCPT\u2010induced testicular cell damage and did not affect the antitumor effect of HCPT. Further analysis found that melatonin therapy suppressed HCPT\u2010induced DNA damage associated with ataxia\u2010telangiectasia mutated\u2010 and Rad3\u2010related and CHK1 phosphorylation levels in the testis. Changes in apoptosis\u2010associated protein levels (Bax, Bcl\u20102, p53, and Cleaved caspase\u20103) and in reactive oxygen species\u2010associated proteins (Nrf2 and Keap1) and index (malondialdehyde\u00a0and glutathione) suggested that melatonin treatment relieved HCPT\u2010induced cell apoptosis and oxidative damage, respectively. Mechanistically, melatonin\u2010activated autophagy proteins (ATG7, Beclin1, and LC3bII\/I) may induce p62\u2010dependent autophagy to degrade Keap1, eliciting Nrf2 from Keap1\u2010Nrf2 interaction to promote antioxidant enzyme expression such as HO\u20101, which would salvage HCPT\u2010induced ROS production and mitochondrial dysfunction. Collectively, this study reveals that melatonin therapy may protect testicular cells from HCPT\u2010induced damage via the activation of autophagy, which alleviates oxidative stress, mitochondrial dysfunction, and cell apoptosis.<\/jats:p>","DOI":"10.1111\/jpi.12959","type":"journal-article","created":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T09:54:36Z","timestamp":1715594076000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Melatonin ameliorates 10\u2010hydroxycamptothecin\u2010induced oxidative stress and apoptosis via autophagy\u2010regulated p62\/Keap1\/Nrf2 pathway in mouse testicular cells"],"prefix":"10.1111","volume":"76","author":[{"given":"Jinmei","family":"Cheng","sequence":"first","affiliation":[{"name":"School of Medicine, Institute of Reproductive Medicine Nantong University Nantong 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