Melatonin stimulates the activity of protective antioxidative enzymes in myocardial cells of rats in the course of doxorubicin intoxication

Abstract

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.

Effects of antenatal, postpartum and post-weaning melatonin supplementation on blood pressure and renal antioxidant enzyme activities in spontaneously hypertensive rats

“…It has been reported that oral melatonin given to SHR, aged 23-25 weeks for 6 weeks, attenuated the raised blood pressure and also lowered the levels of renal TBARS compared to the untreated SHR controls [30]. Melatonin supplementation has been found to reduce the levels of markers of lipid peroxidation in subjects exposed to oxidative stress [12,13,36] but not in normal control rats [12]. The reason for the difference in the results of this study and the others is not clearly apparent.…”

Melatonin suppresses doxorubicin‐induced premature senescence of A549 lung cancer cells by ameliorating mitochondrial dysfunction

“…In addition to its direct ROS‐scavenging activity, melatonin has been shown to increase the expression of antioxidant enzymes such as MnSOD and catalase [55–58]; we did not observe that melatonin increased the MnSOD and catalase protein levels upon DOX treatment (data not shown). Melatonin also exerts some function through the membrane receptors MT1 and MT2 [11].…”

Melatonin preserves superoxide dismutase activity in hypoglossal motoneurons of adult rats following peripheral nerve injury

“…The antioxidative properties of melatonin and its metabolites have been extensively studied and the use of this molecule as a novel neural protector has been widely reported [24–32]. The neuroprotective functions of melatonin are directly attributed to its free radical scavenging ability and indirectly to its positive influence on activating the antioxidative enzyme activities [24, 25, 29, 47].…”