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The glands were exposed to X\u2010radiation at a single dose of 20\u00a0Gy. Ischemic preconditioning was achieved by three min of ischemia and three min of reperfusion, repeated three times before irradiation. Salivary secretion, histological changes, alterations in tight junctions, and the levels of oxidative stress, pro\u2010inflammatory cytokines, and water secretion proteins mediated by the muscarinic acetylcholine M3 subtype receptor were determined at 1 and 12\u00a0weeks post\u2010irradiation. In glands subjected to irradiation only, the secretion, superoxide dismutase activity, tight junction width, acinar cell number, and M3 receptor and aquaporin\u20105 levels were lower at 1 and 12\u00a0weeks than seen in the ischemically preconditioned irradiated glands. In contrast, tumor necrosis factor\u2010\u03b1, malondialdehyde, myeloperoxidase activity, and the expression of the tight junction protein claudin\u20104 were significantly higher in the irradiated only glands. Our study revealed that radiation caused a series of injury\u2010stress responses, especially damage to the water secretion pathway mediated by the M3 receptor that ultimately led to hyposecretion, which might play an important role in the dysfunction of the irradiated only glands. Ischemic preconditioning reduced the radiation\u2010induced injury to submandibular glands and ameliorated salivary hyposecretion.<\/jats:p>","DOI":"10.1111\/eos.12785","type":"journal-article","created":{"date-parts":[[2021,3,31]],"date-time":"2021-03-31T02:16:20Z","timestamp":1617156980000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Effect of ischemic preconditioning on radiation damage to the submandibular gland in rats"],"prefix":"10.1111","volume":"129","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4326-4340","authenticated-orcid":false,"given":"Yan\u2010Hui","family":"Wu","sequence":"first","affiliation":[{"name":"Stomatology School of Xinjiang Medical University Urumqi China"},{"name":"Department of Oral and Maxillofacial Surgery People\u2019s Hospital of Xinjiang Uygur Autonomous Region Urumqi 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