{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T02:59:21Z","timestamp":1772765961312,"version":"3.50.1"},"reference-count":39,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2006,8,1]],"date-time":"2006-08-01T00:00:00Z","timestamp":1154390400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Pineal Research"],"published-print":{"date-parts":[[2006,10]]},"abstract":"<jats:p><jats:bold>Abstract:\u2002<\/jats:bold> Melatonin, the chief product secreted by pineal gland, is capable of reducing free radical damage by acting directly as a free radical scavenger, and indirectly, by stimulating of antioxidant enzymes. Cyclosporine A (CsA) is the most widely used immunosuppressive drug, but its therapeutic use has several side effects including, i.e. nephrotoxicity and cardiotoxicity. This study was designed to examine the beneficial effects of melatonin in preventing CsA\u2010induced cardiotoxicity. Additionally, we investigated the ability of melatonin to protect the rat heart via melatonin receptor. In one group of Wistar rats, melatonin (1\u2003mg\/kg\/day i.p.) was administered concurrently with CsA (15\u2003mg\/kg\/day s.c.) for 21\u2003days. In another group of animals, melatonin was injected with CsA and luzindole, an antagonist of melatonin receptors. Oxidative stress in heart tissue homogenates was estimated using thiobarbituric acid reactive substances (TBARS), reduced glutathione levels and antioxidant enzyme activities including catalase and superoxide dismutase. CsA administration for 21\u2003days produced elevated levels of TBARS, marked depletion of cardiac antioxidant enzymes and caused morphological alterations in myocardial fibers. Melatonin markedly reduced TBARS levels, increased the antioxidant enzyme levels and normalized altered cardiac morphology. The protective effects of melatonin were lost when the animals received the melatonin receptor antagonist. In conclusion our study shows that, (a) melatonin significantly reduces CsA cardiotoxicity, and (b) the reduction in CsA\u2010induced cardiotoxicity was mediated by the binding of melatonin to its membrane receptors.<\/jats:p>","DOI":"10.1111\/j.1600-079x.2006.00368.x","type":"journal-article","created":{"date-parts":[[2006,8,2]],"date-time":"2006-08-02T12:19:17Z","timestamp":1154521157000},"page":"288-295","source":"Crossref","is-referenced-by-count":53,"title":["Beneficial effects of melatonin in protecting against cyclosporine A\u2010induced cardiotoxicity are receptor mediated"],"prefix":"10.1111","volume":"41","author":[{"given":"Rita","family":"Rezzani","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luigi F.","family":"Rodella","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca","family":"Bonomini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandra","family":"Tengattini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rossella","family":"Bianchi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Russel J.","family":"Reiter","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2006,8]]},"reference":[{"key":"e_1_2_6_2_2","first-page":"246","article-title":"Melatonin: lowering the high price of free radicals","volume":"15","author":"Reiter RJ","year":"2000","journal-title":"News Physiol Sci"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-079X.2003.02111.x"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1177\/074873001129002051"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01923947"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1385\/ENDO:27:2:189"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-079X.2005.00304.x"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-079X.2004.00165.x"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1385\/ENDO:27:2:119"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1600-079X.2003.00092.x"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-079X.2005.00248.x"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-079X.2003.00090.x"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF02253360"},{"key":"e_1_2_6_14_2","first-page":"5","article-title":"Curcumin, a diferuloylmethane, attenuates cyclosporine\u2010induced renal dysfunction and oxidative stress in rat kidneys","volume":"15","author":"Tirkey N","year":"2005","journal-title":"BMC Pharmacol"},{"key":"e_1_2_6_15_2","first-page":"301","article-title":"Exploring cyclosporine A\u2010side effects and the protective role\u2010played by antioxidants: the morphological and immunohistochemical studies","volume":"21","author":"Rezzani R","year":"2006","journal-title":"Histol Histopathol"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1472-8206.2005.00361.x"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2005.03.021"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.10216"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tox.2005.04.020"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1369\/jhc.5A6623.2005"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2004.04.005"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.2001.280.5.R1476"},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-079X.2005.00280.x"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-004-4464-6"},{"key":"e_1_2_6_25_2","first-page":"235","article-title":"Cyclosporin and the rat thymus. 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