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Metformin (MET) is a commonly used antidiabetic drug with multiple properties including antiproliferative activity, antioxidant potency, and is used\u00a0in polycystic ovarian syndrome treatment. Here, in this study, we aimed to investigate the effect of different doses of MET on Li\u2010induced hypothyroidism for elucidating its mechanism of action. The obtained results demonstrated the oxidative stress reduction in thyroid tissues upon MET treatment. Besides this, the biochemical analysis revealed a significant reduction in T<jats:sub>3<\/jats:sub> and TSH levels (down to 2\u2009ng\/ml and 0.05\u2009\u00b5U\/ml, respectively) in coordination with an observable reduction in T<jats:sub>4<\/jats:sub> level (up to 2.1\u2009ng\/ml). Also, a significant reduction in Li\u2010related tissue damages including changes in the morphology and the size of follicles, rate of vascularity, detachment of follicular cells, inflammatory cells infiltration, and follicular cells hypertrophy and disruption was observed. Ultimately, regarding the significant improvement in thyroid tissues and valuable antioxidant activity determined in tissues treated with MET, it is concluded that MET co\u2010administration with Li can significantly reduce the negative effects of Li and enhance the efficacy of Li therapy.<\/jats:p>","DOI":"10.1002\/jbt.22977","type":"journal-article","created":{"date-parts":[[2021,12,29]],"date-time":"2021-12-29T07:25:22Z","timestamp":1640762722000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Investigating the protective role of metformin on lithium\u2010induced hypothyroidism"],"prefix":"10.1002","volume":"36","author":[{"given":"Hojjat","family":"Samareh Fekri","sequence":"first","affiliation":[{"name":"Pharmaceutics Research Center, Institute of Neuropharmacology Kerman University of Medical Sciences Kerman Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seide\u2010Fatemeh","family":"Pishnamaz","sequence":"additional","affiliation":[{"name":"Department of Toxicology and Pharmacology, Faculty of Pharmacy Kerman University of Medical Sciences Kerman Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elham","family":"Jafari","sequence":"additional","affiliation":[{"name":"Pathology and Stem Cells Research Center Kerman University of Medical Science Kerman Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mehdi","family":"Ansari","sequence":"additional","affiliation":[{"name":"Department of Drug and Food Control, Faculty of Pharmacy Kerman University of Medical Sciences Kerman Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohsen","family":"Doostmohammadi","sequence":"additional","affiliation":[{"name":"Pharmaceutics Research Center, Institute of Neuropharmacology Kerman University of Medical Sciences Kerman Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammad","family":"Mohajeri","sequence":"additional","affiliation":[{"name":"Department of Toxicology and Pharmacology, Faculty of Pharmacy Kerman University of Medical Sciences Kerman Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9014-802X","authenticated-orcid":false,"given":"Hamid\u2010Reza","family":"Rahimi","sequence":"additional","affiliation":[{"name":"Pharmaceutics Research Center, Institute of Neuropharmacology Kerman University of Medical Sciences Kerman Iran"},{"name":"Department of Toxicology and Pharmacology, Faculty of Pharmacy Kerman University of Medical Sciences Kerman Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,12,28]]},"reference":[{"key":"e_1_2_9_2_1","first-page":"22312","volume":"10","author":"Kalantari H.","year":"2015","journal-title":"J. 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