{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T19:48:04Z","timestamp":1776196084318,"version":"3.50.1"},"reference-count":31,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2025,9,4]],"date-time":"2025-09-04T00:00:00Z","timestamp":1756944000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Department of Radiation Oncology","award":["P30 CA008748"],"award-info":[{"award-number":["P30 CA008748"]}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute Core Center","doi-asserted-by":"publisher","award":["P30 CA008748"],"award-info":[{"award-number":["P30 CA008748"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Radiation-induced salivary gland (SG) hypofunction is mediated via microvascular dysfunction and radical oxygen species. N-acetylcysteine amide (NACA) has shown antioxidant properties with low toxicity. We explored NACA\u2019s potential as a radioprotector of SG function. Methods: Bovine aortic endothelial cells (BAECs) were treated with NACA before irradiation with a single 10 Gy dose. Apoptosis was assessed by bis-benzimide staining and quantified via fluorescence microscopy. In vivo, NACA was administered to mice prior to a single 15 Gy head and neck irradiation. Eight weeks post-irradiation, saliva production was measured using pilocarpine stimulation; lysozyme levels were analyzed by ELISA. SGs were collected for immunohistochemistry. Results: BAEC apoptosis was substantially lower in NACA-treated cells vs. radiation-only (10% vs. 23%). In vivo, mice lost significant weight and developed severe hair loss eight weeks post-irradiation\u2014attenuated by NACA pretreatment. Saliva production was reduced by 72% post-radiation, with a corresponding drop in lysozyme. NACA increased salivary flow by 42% and prevented lysozyme reduction. Post-radiation decline in microvessel density was also prevented by NACA. Conclusions: These outcomes suggest NACA may serve as a radioprotector of SG function in patients undergoing radiotherapy for head and neck cancer.<\/jats:p>","DOI":"10.3390\/cancers17172902","type":"journal-article","created":{"date-parts":[[2025,9,4]],"date-time":"2025-09-04T10:55:37Z","timestamp":1756983337000},"page":"2902","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["N-Acetylcysteine Amide Is a Potential Novel Radioprotector of Salivary Gland Function"],"prefix":"10.3390","volume":"17","author":[{"given":"Amit","family":"Ritter","sequence":"first","affiliation":[{"name":"Department of Otolaryngology Head and Neck Surgery, Rabin Medical Center, Petah Tikva 4941492, Israel"},{"name":"Gray Faculty of Medical & Health Sciences, Tel-Aviv University, Tel Aviv 6997801, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elad","family":"Hikri","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology Head and Neck Surgery, Rabin Medical Center, Petah Tikva 4941492, Israel"},{"name":"Gray Faculty of Medical & Health Sciences, Tel-Aviv University, Tel Aviv 6997801, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9666-9398","authenticated-orcid":false,"given":"Hongyan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ela","family":"Markovsky","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gideon","family":"Bachar","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology Head and Neck Surgery, Rabin Medical Center, Petah Tikva 4941492, Israel"},{"name":"Gray Faculty of Medical & Health Sciences, Tel-Aviv University, Tel Aviv 6997801, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noga","family":"Kurman","sequence":"additional","affiliation":[{"name":"Gray Faculty of Medical & Health Sciences, Tel-Aviv University, Tel Aviv 6997801, Israel"},{"name":"Davidoff Cancer Center, Rabin Medical Center, Petah Tikva 4941492, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aron","family":"Popovtzer","sequence":"additional","affiliation":[{"name":"Department of Oncology, Hadassah-Hebrew University Medical Center, Jerusalem 9112102, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adriana","family":"Haimovitz-Friedman","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7462-1086","authenticated-orcid":false,"given":"Aviram","family":"Mizrachi","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology Head and Neck Surgery, Rabin Medical Center, Petah Tikva 4941492, Israel"},{"name":"Gray Faculty of Medical & Health Sciences, Tel-Aviv University, Tel Aviv 6997801, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1016\/S0140-6736(06)69121-6","article-title":"Hyperfractionated or accelerated radiotherapy in head and neck cancer: A meta-analysis","volume":"368","author":"Bourhis","year":"2006","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.radonc.2009.04.014","article-title":"Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): An update on 93 randomised trials and 17,346 patients","volume":"92","author":"Pignon","year":"2009","journal-title":"Radiother Oncol. 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