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The current work aimed to study the toxic effects of lithium on the heart of adult albino rats and its molecular mechanisms and the ameliorating effect of N-acetyl cysteine (NAC). Sixty adult male Wistar albino rats were classified into four groups; control, NAC-treated received NAC 500 mg\/kg\/week dissolved in 1 ml 0.9% sodium chloride intraperitoneal, lithium-treated received 52.5 mg\/kg\/day of lithium carbonate dissolved in 1 ml 0.9% sodium chloride orally by gavage, and lithium-and-NAC-treated (group IV) received lithium and NAC in the previous doses. After 12 weeks, the rats of group III showed a significant accumulation of ascites and a decrease in the mean arterial blood pressure and electrocardiographic (ECG) findings of ischemia and arrhythmia. In addition, there was an elevation in cardiac biomarkers creatine kinase MB (CK-MB), cardiac troponin I (cTnI), and several histological lesions with a significant increase in the area % of Van Gieson, endothelial nitric oxide synthase (eNOS), and 8-hydroxy-2\u2032-deoxyguanosine (8-OHdG) immunoreaction. There was significant upregulation of microRNA-1, microRNA-21 (miRNA-21), and microRNA-29 (miRNA-29). MiRNA-21 was strongly positively correlated to the area % of 8-OHdG, while miRNA-29 was strongly positively correlated to the area % of Van Gieson staining. NAC significantly improved the cardiotoxic effects of lithium. Being a nontoxic and safe antioxidant, NAC can be used to ameliorate lithium-induced cardiac injury.<\/jats:p>","DOI":"10.1177\/0960327119897759","type":"journal-article","created":{"date-parts":[[2020,1,13]],"date-time":"2020-01-13T08:17:02Z","timestamp":1578903422000},"page":"696-711","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":13,"title":["The molecular mechanisms of lithium-induced cardiotoxicity in male rats and its amelioration by\n                    <i>N<\/i>\n                    -acetyl cysteine"],"prefix":"10.1177","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9923-6114","authenticated-orcid":false,"given":"Omaima I","family":"Abdel Hamid","sequence":"first","affiliation":[{"name":"Department of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Zagazig University, Zagazig, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ebtesam 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