The protective effect of melatonin on adriamycin-induced acute cardiac injury.
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).


CONCLUSIONS
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.
Koçak
Gülendam
G
Inönü University Faculty of Medicine, Malatya, Turkey. gul_endam@yahoo.com
Erbil
K Mine
KM
Ozdemir
Ilknur
I
Aydemir
Songül
S
Sunar
Bülbin
B
Tuncel
Mürvet
M
Atalay
Semra
S
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000633:toxicity*; D009202:Cardiomyopathies / Q000139:chemically induced / Q000517:prevention & control*; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000008:administration & dosage / Q000633:toxicity*; D016166:Free Radical Scavengers / Q000008:administration & dosage / Q000627:therapeutic use*; D007274:Injections, Intraperitoneal; D015227:Lipid Peroxidation; D008550:Melatonin / Q000008:administration & dosage / Q000627:therapeutic use*; D009206:Myocardium / Q000378:metabolism / Q000648:ultrastructure; D051381:Rats; D017208:Rats, Wistar
D000903:Antibiotics, Antineoplastic; D002316:Cardiotonic Agents; D016166:Free Radical Scavengers; D004317:Doxorubicin; D008550:Melatonin