Beneficial effects of melatonin in protecting against cyclosporine A-induced cardiotoxicity are receptor mediated

Rita Rezzani, Luigi F. Rodella, Francesca Bonomini, Sandra Tengattini, Rossella Bianchi, Russel J Reiter

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

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-induced cardiotoxicity. Additionally, we investigated the ability of melatonin to protect the rat heart via melatonin receptor. In one group of Wistar rats, melatonin (1 mg/kg/day i.p.) was administered concurrently with CsA (15 mg/kg/day s.c.) for 21 days. 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 days 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-induced cardiotoxicity was mediated by the binding of melatonin to its membrane receptors.

Original languageEnglish (US)
Pages (from-to)288-295
Number of pages8
JournalJournal of Pineal Research
Volume41
Issue number3
DOIs
StatePublished - Oct 2006

Fingerprint

Melatonin
Cyclosporine
Melatonin Receptors
Thiobarbituric Acid Reactive Substances
Antioxidants
Enzymes
Cardiotoxicity
Free Radical Scavengers
Pineal Gland
Therapeutic Uses
Immunosuppressive Agents
Catalase
Superoxide Dismutase
Free Radicals
Glutathione
Wistar Rats
Oxidative Stress
Membranes

Keywords

  • Cardiotoxicity
  • Cyclosporine A
  • Luzindole
  • Melatonin
  • Oxidative stress

ASJC Scopus subject areas

  • Endocrinology

Cite this

Beneficial effects of melatonin in protecting against cyclosporine A-induced cardiotoxicity are receptor mediated. / Rezzani, Rita; Rodella, Luigi F.; Bonomini, Francesca; Tengattini, Sandra; Bianchi, Rossella; Reiter, Russel J.

In: Journal of Pineal Research, Vol. 41, No. 3, 10.2006, p. 288-295.

Research output: Contribution to journalArticle

Rezzani, Rita ; Rodella, Luigi F. ; Bonomini, Francesca ; Tengattini, Sandra ; Bianchi, Rossella ; Reiter, Russel J. / Beneficial effects of melatonin in protecting against cyclosporine A-induced cardiotoxicity are receptor mediated. In: Journal of Pineal Research. 2006 ; Vol. 41, No. 3. pp. 288-295.
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