The effects of melatonin on glutathione peroxidase activity in serum and erythrocytes after adriamycin in normal and pinealectomised rats

Abstract

Introduction: Adriamycin (ADR) is a potent chemotherapeutic agent, effective in the treatment of leukaemias, lymphomas and many solid tumours. However, its clinical usage is often limited by cardiotoxicity, induced by oxygen radical damage of the membrane lipids. Melatonin (MEL) is a well-known antioxidant. It has been shown that MEL can scavenge free radicals, both directly and indirectly, stimulating the activity of antioxidative enzymes such as glutathione peroxidase (GSH-Px).
The aim of the study: The aim of the study was to examine the effect of MEL on serum and erythrocyte GSH-Px activity after ADR in normal and pinealectomised rats.
Material and methods: Wistar rats were divided into the three groups: control animals (Intact), sham-operated (Sham-PX) and pinealectomised (Px). Each of the groups was divided into four subgroups, injected with: 1 - saline, 2 - MEL, 3 - ADR and 4 - ADR + MEL. ADR was administered 2 months after Px as a single dose (15 mg/kg, i.p.) 1 hour after the fourth melatonin injection. Melatonin (5 mg/kg, i.p.) was administered for 4 days before and 2 days after ADR. After 6 days of treatment, the rats were killed by decapitation. Their blood was collected for measurements.
Results: In serum GSH-Px activity decreased in all the groups after ADR. Pinealectomy decreased the activity of the enzyme in all the groups of animals examined. In erythrocytes GSH-Px decreased after ADR in the Px-animals. The effect of pinealectomy on erythrocyte GSH-Px activity was not as strongly expressed as serum GSH-Px activity. MEL did not change GSH-Px activity after ADR.
Conclusion: Melatonin, in pharmacological concentrations, did not influence the activity of GSH-Px, either in normal or in pinealectomised rats after ADR. A deficiency of endogenous melatonin production may inhibit GSH-Px activity.