Korean J Physiol Pharmacol.
2001 Aug;5(4):333-342.
The protective effect of melatonin administration against adriamycin-induced cardiotoxicity in rats
- Affiliations
-
- 1Department of Physiology and Biophysics, College of Medicine, Inje University, Busan, South Korea. phykimey@ijnc.inje.ac.kr
Abstract
- Adriamycin is a commonly used chemotherapeutic agent for cancer,
including acute leukemia, lymphoma, and a number of solid human tumors.
However, recent studies have recognized severe cardiotoxicity after an
acute dose, which are likely the result of generation of free radicals
and lipid peroxidation. Therefore, the clinical uses of adriamycin have
been limited. Melatonin, the pineal gland hormone known for its ability
to modulate circardian rhythm, has recently been studied in its several
functions, including cancer growth inhibition, stimulating the immune
system, and acting as an antioxidant and radical scavenging effects. In
the present study, we evaluated the effect of melatonin administration on
adriamycin-induced cardiotoxicity in rat. Heart slices were prepared
using a Stadie-Riggs microtome for the measurement of malondialdehyde
(MDA) content used as an index of lipid peroxidation and lactate
dehydrogenase (LDH) release as an indicator of lethal cell injury.
Serious adriamycin-induced lethality was observed in rat by a single
intraperitoneal injection in a dose-dependent manner. A single injection
of adriamycin (25 mg/kg, i.p.) induced a lethality rate of 86%, with
melatonin (10 mg/kg s.c. for 6 days) treatment reducing the
adriamycin-induced lethality rate to 20%. The severe body weight loss
caused by adriamycin was also significantly attenuated by melatonin
treatment. Treatment of melatonin marked reduced adriamycin-induced the
levels of MDA formation and LDH release. A cell damage indicated by the
loss of myofibrils, swelling of the mitochondria as well as cytoplasmic
vacuolization was seen in adriamycin-treated group. Melatonin attenuated
the adriamycin-induced structural alterations. These data provide
evidence that melatonin prevents adriamycin-induced cardiotoxicity and
might serve as a combination with adriamycin to limit free
radical-mediated cardiotoxicity.