Melatonin stimulates the activity of protective antioxidative enzymes in myocardial cells of rats in the course of doxorubicin intoxication.
The study aimed at determining the effect of melatonin on the activity of protective antioxidative enzymes in the heart and of lipid peroxidation products in the course of intoxication with doxorubicin (DOX). The rats were categorized into four groups, receiving: 0.9% NaCl i.p. (NaCl control); melatonin [20 mg/kg body weight (b.w.)] s.c. (control Mel); DOX (2.5 mg/kg b.w.) i.p.; melatonin plus DOX in doses as above. All the substances were administered once in a week for four consecutive weeks. Homogenates of heart tissue were examined for activities of glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT), levels of reduced glutathione (GSH) and of lipid peroxidation indices (MDA + 4-HDA). Administration of melatonin alone did not induce alterations in levels of MDA + 4-HDA, GSH, or in activity of GPx, SOD or CAT, as compared to the group receiving 0.9% NaCl. GSH levels decreased following DOX but remained at normal levels following DOX and melatonin. The level of MDA + 4-HDA increased following DOX, as compared with the control, a change prevented by the combination of DOX + melatonin. Activities of GPx, SOD and CAT were higher in groups receiving DOX and/or DOX plus melatonin than in control groups. Activity of CAT and the level of GSH in the group receiving DOX plus melatonin were significantly higher than in the group intoxicated with DOX alone. The obtained results demonstrate that, when given in parallel with DOX, melatonin protects cardiomyocytes from damaging effects of the cytostatic drug (reflected by the levels of MDA + 4-HDA). The protective effect resulted, in part from the augmented levels of GSH and from stimulation of CAT activity by melatonin in cardiomyocytes subjected to the action of DOX.
Dziegiel
Piotr
P
Department of Histology and Embryology, Wrocław Medical University, Wrocław, Poland. piotr@hist.am.wroc.pl
Murawska-Ciałowicz
Eugenia
E
Jethon
Zbigniew
Z
Januszewska
Lidia
L
Podhorska-Okołów
Marzena
M
Surowiak
Paweł
P
Zawadzki
Marcin
M
Rabczyński
Jerzy
J
Zabel
Maciej
M
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects*; D000975:Antioxidants / Q000378:metabolism; D002374:Catalase / Q000187:drug effects; D004317:Doxorubicin / Q000009:adverse effects*; D020536:Enzyme Activators / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000187:drug effects; D008550:Melatonin / Q000494:pharmacology*; D032383:Myocytes, Cardiac / Q000187:drug effects*; D051381:Rats; D011915:Rats, Inbred BUF; D013482:Superoxide Dismutase / Q000187:drug effects
D000903:Antibiotics, Antineoplastic; D000975:Antioxidants; D020536:Enzyme Activators; D004317:Doxorubicin; D002374:Catalase; D005979:Glutathione Peroxidase; C080439:selenium-independent glutathione peroxidase; D013482:Superoxide Dismutase; D005978:Glutathione; D008550:Melatonin