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Although either iron chelators or antioxidants provide cardioprotection, a comparison of the efficacy of deferoxamine (DFO), deferiprone (DFP), deferasirox (DFX), N-acetyl cysteine (NAC) or a combination of DFP plus NAC on cardiac [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>homeostasis in chronic iron overload has never been investigated. Male Wistar rats were fed with either a normal diet or a high iron (HFe) diet for 4 months. At 2 months, HFe rats were divided into 6 groups and treated with either a vehicle, DFO (25\u2009mg\/kg\/day), DFP (75\u2009mg\/kg\/day), DFX (20\u2009mg\/kg\/day), NAC (100\u2009mg\/kg\/day), or combined DFP plus NAC. At 4 months, the number of cardiac T-type calcium channels was increased, whereas cardiac sarcoplasmic-endoplasmic reticulum Ca<jats:sup>2+<\/jats:sup>ATPase (SERCA) was decreased, leading to cardiac iron overload and impaired cardiac [Ca<jats:sup>2+<\/jats:sup>]i homeostasis. All pharmacological interventions restored SERCA levels. Although DFO, DFP, DFX or NAC alone shared similar efficacy in improving cardiac [Ca<jats:sup>2+<\/jats:sup>]i homeostasis, only DFP\u2009+\u2009NAC restored cardiac [Ca<jats:sup>2+<\/jats:sup>]i homeostasis, leading to restoring left ventricular function in the HFe-fed rats. Thus, the combined DFP\u2009+\u2009NAC was more effective than any monotherapy in restoring cardiac [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>homeostasis, leading to restored myocardial contractility in iron-overloaded rats.<\/jats:p>","DOI":"10.1038\/srep44460","type":"journal-article","created":{"date-parts":[[2017,3,13]],"date-time":"2017-03-13T13:46:21Z","timestamp":1489412781000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["Restoring the impaired cardiac calcium homeostasis and cardiac function in iron overload rats by the combined deferiprone and N-acetyl cysteine"],"prefix":"10.1038","volume":"7","author":[{"given":"Suwakon","family":"Wongjaikam","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sirinart","family":"Kumfu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juthamas","family":"Khamseekaew","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siriporn C.","family":"Chattipakorn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nipon","family":"Chattipakorn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2017,3,13]]},"reference":[{"key":"BFsrep44460_CR1","first-page":"178","volume":"34","author":"A von Herbay","year":"1996","unstructured":"von Herbay, A. et al. -Cardiomyopathy as the cause of death in genetic hemochromatosis. 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