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    The protective effect of melatonin on adriamycin-induced acute cardiac injury
    (Elsevier Science Inc, 2003) Koçak, G; Erbil, KM; Özdemir, I; Aydemir, S; Sunar, B; Tuncel, M; Atalay, S
    BACKGROUND: Cardiotoxicity is the main complication of adriamycin (ADR), which is a widely used chemotherapeutic agent. OBJECTIVE: To examine the potential cardioprotective effect of melatonin (MEL) on acute ADR cardiotoxicity in a rat model. METHODS: Cardioprotection was assessed on the basis of myocardial lipid peroxidation and ultrastructure. Rats were given MEL at a daily dose of 5 mg/kg and ADR 15 mg/kg, intraperitoneally. The MEL-1 group rats received one dose and the MEL-7 group rats six daily doses of MEL and were sacrificed at the end of one and seven days, respectively. Rats in the ADR-1 and ADR-7 groups were each given a single dose of ADR, and were then sacrificed 24 h and seven days later, respectively. The MEL+ADR-1 group rats received one dose each of ADR and MEL simultaneously and were sacrificed 24 h later. The MEL+ADR-7 group received a single dose of ADR plus a daily MEL dose for six consecutive days, and were sacrificed seven days after the ADR injection. RESULTS: Lipid peroxidation products were elevated in both ADR-1 and ADR-7 groups, and this elevation was significantly inhibited by MEL treatment. Electron microscopy confirmed that ADR was positively cardiotoxic after one and seven days of exposure. The extent of ADR-induced myocardial damage was markedly reduced when MEL was combined with ADR (MEL+ADR-1 and MEL+ADR-7). CONCLUSION: The results suggest that MEL is highly efficacious at reducing the acute cardiotoxic effects of high dose ADR, and that it acts by preventing lipid peroxidation.