{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:38:30Z","timestamp":1769906310675,"version":"3.49.0"},"reference-count":49,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2020,6,10]],"date-time":"2020-06-10T00:00:00Z","timestamp":1591747200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Radioiodine (RI) therapy is known to cause salivary gland (SG) dysfunction. The effects of antioxidants on RI-induced SG damage have not been well described. This study was performed to investigate the radioprotective effects of alpha lipoic acid (ALA) administered prior to RI therapy in a mouse model of RI-induced sialadenitis. Four-week-old female C57BL\/6 mice were divided into four groups (n = 10 per group): group I, normal control; group II, ALA alone (100 mg\/kg); group III, RI alone (0.01 mCi\/g body weight, orally); and group IV, ALA + RI (ALA at 100 mg\/kg, 24 h and 30 min before RI exposure at 0.01 mCi\/g body weight). The animals in these groups were divided into two subgroups and euthanized at 30 or 90 days post-RI treatment. Changes in salivary 99mTc pertechnetate uptake and excretion were tracked by single-photon emission computed tomography. Salivary histological examinations and TUNEL assays were performed. The 99mTc pertechnetate excretion level recovered in the ALA treatment group. Salivary epithelial (aquaporin 5) cells of the ALA + RI group were protected from RI damage. The ALA + RI group exhibited more mucin-containing parenchyma and less fibrotic tissues than the RI only group. Fewer apoptotic cells were observed in the ALA + RI group compared to the RI only group. Pretreatment with ALA before RI therapy is potentially beneficial in protecting against RI-induced salivary dysfunction.<\/jats:p>","DOI":"10.3390\/ijms21114136","type":"journal-article","created":{"date-parts":[[2020,6,10]],"date-time":"2020-06-10T07:13:16Z","timestamp":1591773196000},"page":"4136","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Protective Effect of Alpha-Lipoic Acid on Salivary Dysfunction in a Mouse Model of Radioiodine Therapy-Induced Sialoadenitis"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6285-8262","authenticated-orcid":false,"given":"Jung Hwa","family":"Jung","sequence":"first","affiliation":[{"name":"Department of Internal medicine, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital, Jinju 52727, Korea"},{"name":"Institute of Health Science, Gyeongsang National University School of Medicine, Jinju 52727, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2913-6481","authenticated-orcid":false,"given":"Jin Hyun","family":"Kim","sequence":"additional","affiliation":[{"name":"Institute of Health Science, Gyeongsang National University School of Medicine, Jinju 52727, Korea"},{"name":"Biomedical Research Institute, Gyeongsang National University Hospital, Jinju 52727, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Myeong Hee","family":"Jung","sequence":"additional","affiliation":[{"name":"Biomedical Research Institute, Gyeongsang National University Hospital, Jinju 52727, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seung Won","family":"Kim","sequence":"additional","affiliation":[{"name":"Animal Molecular Imaging Team, Research Core Center, National Cancer Center, Goyang 10408, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8015-6061","authenticated-orcid":false,"given":"Bae Kwon","family":"Jeong","sequence":"additional","affiliation":[{"name":"Institute of Health Science, Gyeongsang National University School of Medicine, Jinju 52727, Korea"},{"name":"Department of Radiation Oncology, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital, Jinju 52727, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seung Hoon","family":"Woo","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology-Head and Neck Surgery, Dankook University, Cheonan 31116, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,6,10]]},"reference":[{"key":"ref_1","first-page":"738","article-title":"Salivary and lacrimal gland dysfunction (sicca syndrome) after radioiodine therapy","volume":"42","author":"Solans","year":"2001","journal-title":"J. Nucl. Med."},{"key":"ref_2","first-page":"1551","article-title":"Intermediate and long-term side effects of high-dose radioiodine therapy for thyroid carcinoma","volume":"39","author":"Alexander","year":"1998","journal-title":"J. Nucl. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1089\/105072504322880373","article-title":"Quality of life with well-differentiated thyroid cancer: Treatment toxicities and their reduction","volume":"14","author":"Mendoza","year":"2004","journal-title":"Thyroid"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1097\/00006231-199608000-00006","article-title":"Quantitative salivary gland scintigraphy in the diagnosis of parenchymal damage after treatment with radioiodine","volume":"17","author":"Bohuslavizki","year":"1996","journal-title":"Nucl. Med. Commun."},{"key":"ref_5","first-page":"261","article-title":"Does lemon candy decrease salivary gland damage after radioiodine therapy for thyroid cancer?","volume":"46","author":"Nakada","year":"2005","journal-title":"J. Nucl. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1089\/thy.2014.0572","article-title":"Sialendoscopy for Patients with Radioiodine-Induced Sialadenitis and Xerostomia","volume":"25","author":"Bhayani","year":"2015","journal-title":"Thyroid"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1007\/s00066-005-1353-3","article-title":"Amifostine is a potent radioprotector of salivary glands in radioiodine therapy. Structural and ultrastructural findings","volume":"181","author":"Kutta","year":"2005","journal-title":"Strahlenther. Onkol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"15105","DOI":"10.18632\/oncotarget.7874","article-title":"Effect of alpha-lipoic acid on radiation-induced small intestine injury in mice","volume":"7","author":"Jeong","year":"2016","journal-title":"Oncotarget"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Jung, J.H., Jung, J., Kim, S.K., Woo, S.H., Kang, K.M., Jeong, B.K., Jung, M.H., Kim, J.H., and Hahm, J.R. (2014). Alpha lipoic acid attenuates radiation-induced thyroid injury in rats. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0112253"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"29143","DOI":"10.18632\/oncotarget.8661","article-title":"Protective effects of alpha lipoic acid on radiation-induced salivary gland injury in rats","volume":"7","author":"Kim","year":"2016","journal-title":"Oncotarget"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"72739","DOI":"10.18632\/oncotarget.20286","article-title":"Alpha lipoic acid attenuates radiation-induced oral mucositis in rats","volume":"8","author":"Kim","year":"2017","journal-title":"Oncotarget"},{"key":"ref_12","first-page":"570","article-title":"Lipoic acid\u2014The drug of the future?","volume":"57","author":"Bilska","year":"2005","journal-title":"Pharmacol. Rep."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1111\/j.1440-1681.2007.04810.x","article-title":"Alpha-lipoic acid protects against renal ischaemia-reperfusion injury in rats","volume":"35","author":"Sehirli","year":"2008","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"ref_14","first-page":"145","article-title":"The effects of alpha-lipoic acid on nitric oxide synthetase dispersion in penile function in streptozotocin-induced diabetic rats","volume":"27","author":"Hurdag","year":"2005","journal-title":"Int J. Tissue React."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1159\/000081783","article-title":"The protective effect of alpha-lipoic acid against oxidative damage in rabbit conjunctiva and cornea exposed to ultraviolet radiation","volume":"219","author":"Demir","year":"2005","journal-title":"Ophthalmologica"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1007\/s00259-003-1427-3","article-title":"Iodine-131 treatment and chromosomal damage: In vivo dose-effect relationship","volume":"31","author":"Erselcan","year":"2004","journal-title":"Eur J. Nucl Med. Mol. Imaging"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/S0889-8588(18)30244-2","article-title":"Cellular, molecular, and carcinogenic effects of radiation","volume":"7","author":"Little","year":"1993","journal-title":"Hematol. Oncol. Clin. N. Am."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.2217\/fon.13.79","article-title":"Radioprotective agents for the prevention of side effects induced by radioiodine-131 therapy","volume":"9","author":"Noaparast","year":"2013","journal-title":"Future Oncol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1016\/j.drudis.2007.07.017","article-title":"Trends in the development of radioprotective agents","volume":"12","author":"Hosseinimehr","year":"2007","journal-title":"Drug Discov. Today"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.archoralbio.2005.06.008","article-title":"Evaluation of radioprotective effect of vitamin E in salivary dysfunction in irradiated rats","volume":"51","author":"Ramos","year":"2006","journal-title":"Arch. Oral. Biol."},{"key":"ref_21","first-page":"185","article-title":"Radioprotective, anticarcinogenic and antioxidant properties of the Indian holy basil, Ocimum sanctum (Tulasi)","volume":"39","year":"2001","journal-title":"Indian J. Exp. Biol."},{"key":"ref_22","first-page":"3","article-title":"Differential protection against cytotoxic chemotherapeutic effects on bone marrow CFUs by Wr-2721","volume":"4","author":"Wasserman","year":"1981","journal-title":"Cancer Clin. Trials"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1487","DOI":"10.1016\/0360-3016(86)90200-2","article-title":"Comparative biodistribution and radioprotection studies with three radioprotective drugs in mouse tumors","volume":"12","author":"Rasey","year":"1986","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_24","first-page":"211","article-title":"The role of WR-2721 in radiotherapy and\/or chemotherapy","volume":"3","author":"Yuhas","year":"1980","journal-title":"Cancer Clin. Trials"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1555","DOI":"10.1016\/0360-3016(84)90502-9","article-title":"Radioprotection by WR-2721 of gamma-irradiated rat parotid gland: Effect on gland weight and secretion at 8-10 days post irradiation","volume":"10","author":"Menard","year":"1984","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1007\/s00520-010-0827-8","article-title":"A systematic review of salivary gland hypofunction and xerostomia induced by cancer therapies: Prevalence, severity and impact on quality of life","volume":"18","author":"Jensen","year":"2010","journal-title":"Support. Care Cancer"},{"key":"ref_27","first-page":"737","article-title":"Radioprotective effect of Ocimum sanctum and amifostine on the salivary gland of rats after therapeutic radioiodine exposure","volume":"26","author":"Joseph","year":"2011","journal-title":"Cancer Biother. Radiopharm."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1170","DOI":"10.1158\/0008-5472.CAN-15-1671","article-title":"Radiation-Induced Loss of Salivary Gland Function Is Driven by Cellular Senescence and Prevented by IL6 Modulation","volume":"76","author":"Marmary","year":"2016","journal-title":"Cancer Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1097\/00006231-200606000-00004","article-title":"Quantitative evaluation of salivary gland dysfunction after radioiodine therapy using salivary gland scintigraphy","volume":"27","author":"Raza","year":"2006","journal-title":"Nucl. Med. Commun."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1310","DOI":"10.1172\/JCI112954","article-title":"99mTc-pertechnetate uptake in parotid acinar cells by the Na+\/K+\/Cl\u2212 co-transport system","volume":"79","author":"Helman","year":"1987","journal-title":"J. Clin. Investig."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1699","DOI":"10.1007\/s10067-012-2076-3","article-title":"Semi-quantitative evaluation of salivary gland function in Sjogren\u2019s syndrome using salivary gland scintigraphy","volume":"31","author":"Zou","year":"2012","journal-title":"Clin. Rheumatol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"335","DOI":"10.21053\/ceo.2019.00542","article-title":"Intraoperative Neuromonitoring for Thyroid Surgery: The Proven Benefits and Limitations","volume":"12","author":"Choi","year":"2019","journal-title":"Clin. Exp. Otorhinolaryngol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"217","DOI":"10.21053\/ceo.2018.01207","article-title":"Development of a Novel Intraoperative Neuromonitoring System Using a Surface Pressure Sensor to Detect Muscle Movement: A Rabbit Model Study","volume":"12","author":"Sung","year":"2019","journal-title":"Clin. Exp. Otorhinolaryngol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"420","DOI":"10.21053\/ceo.2019.00423","article-title":"Development of a Novel Intraoperative Neuromonitoring System Using an Accelerometer Sensor in Thyroid Surgery: A Porcine Model Study","volume":"12","author":"Sung","year":"2019","journal-title":"Clin. Exp. Otorhinolaryngol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1","DOI":"10.21053\/ceo.2018.00766","article-title":"Robotic and Endoscopic Thyroid Surgery: Evolution and Advances","volume":"12","author":"Tae","year":"2019","journal-title":"Clin. Exp. Otorhinolaryngol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"58","DOI":"10.21053\/ceo.2017.00472","article-title":"Number of Metastatic Lymph Nodes and Ratio of Metastatic Lymph Nodes to Total Number of Retrieved Lymph Nodes Are Risk Factors for Recurrence in Patients With Clinically Node Negative Papillary Thyroid Carcinoma","volume":"11","author":"Zheng","year":"2018","journal-title":"Clin. Exp. Otorhinolaryngol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"194","DOI":"10.21053\/ceo.2019.01634","article-title":"The Effect of Prophylactic Central Neck Dissection During Hemithyroidectomy on Locoregional Recurrence in Patients With Papillary Thyroid Carcinoma: A Meta-Analysis","volume":"13","author":"Ahn","year":"2020","journal-title":"Clin. Exp. Otorhinolaryngol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1016\/j.ijrobp.2004.12.051","article-title":"On the mechanism of salivary gland radiosensitivity","volume":"62","author":"Konings","year":"2005","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1089\/105072503321582060","article-title":"Radioactive iodine and the salivary glands","volume":"13","author":"Mandel","year":"2003","journal-title":"Thyroid"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1111\/j.1749-6632.1993.tb18338.x","article-title":"Principles of saliva secretion","volume":"694","author":"Baum","year":"1993","journal-title":"Ann. N.Y. Acad. Sci."},{"key":"ref_41","first-page":"611","article-title":"Chemopreventive potential of alpha lipoic acid in the treatment of colon and cervix cancer cell lines","volume":"115","author":"Damnjanovic","year":"2014","journal-title":"Bratisl. Lek. Listy"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.mce.2015.10.005","article-title":"Alpha lipoic acid inhibits proliferation and epithelial mesenchymal transition of thyroid cancer cells","volume":"419","author":"Jeon","year":"2016","journal-title":"Mol. Cell Endocrinol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"17934","DOI":"10.4238\/2015.December.22.18","article-title":"Effect of lipoic acid combined with paclitaxel on breast cancer cells","volume":"14","author":"Li","year":"2015","journal-title":"Genet. Mol. Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1159\/000443994","article-title":"Chemopreventive Effects of Alpha Lipoic Acid on Obesity-Related Cancers","volume":"68","author":"Moon","year":"2016","journal-title":"Ann. Nutr. Metab."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1445","DOI":"10.3892\/ijo.2016.3624","article-title":"alpha-Lipoic acid sensitizes lung cancer cells to chemotherapeutic agents and anoikis via integrin beta1\/beta3 downregulation","volume":"49","author":"Puchsaka","year":"2016","journal-title":"Int. J. Oncol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.yrtph.2006.06.004","article-title":"Safety evaluation of alpha-lipoic acid (ALA)","volume":"46","author":"Cremer","year":"2006","journal-title":"Regul. Toxicol. Pharmacol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.yrtph.2006.06.003","article-title":"Long-term safety of alpha-lipoic acid (ALA) consumption: A 2-year study","volume":"46","author":"Cremer","year":"2006","journal-title":"Regul. Toxicol. Pharmacol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1125.e3","DOI":"10.1016\/j.ajem.2018.03.022","article-title":"Alpha lipoic acid intoxication: An adult","volume":"36","author":"Emir","year":"2018","journal-title":"Am. J. Emerg. Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"138719","DOI":"10.1155\/2013\/138719","article-title":"Alpha-lipoic acid attenuates renal injury in rats with obstructive nephropathy","volume":"2013","author":"Wongmekiat","year":"2013","journal-title":"Biomed. Res. Int."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/11\/4136\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:37:21Z","timestamp":1760175441000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/11\/4136"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6,10]]},"references-count":49,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2020,6]]}},"alternative-id":["ijms21114136"],"URL":"https:\/\/doi.org\/10.3390\/ijms21114136","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,6,10]]}}}