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Melatonin metabolite 6-Sulfatoxymelatonin, Cu/Zn superoxide dismutase, oxidized LDL and malondialdehyde in unstable angina

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Abstract

Background

Melatonin, a lypophylic antioxidant, was reported to be low in patients suffering from myocardial infarction, a disease due to coronary atherosclerosis associated with increased reactive oxygen species. Studies carried out till now have shown association of either melatonin or another antioxidant Cu/Zn SOD in patients suffering from coronary artery disease but not both together. Concurrent measurement of these two parameters will reveal the relationship if any in the probable causation of the disease.

Methods

We estimated the serum malondialdeheyde, oxidized LDL, lipid profile and activity of Cu/Zn superoxide dismutase and the concentration of urinary metabolite of melatonin, 6-Sulfatoxymelatonin in 24 h urine sample collected from 21 patients suffering from unstable angina and 30 control subjects.

Results

A statistically significant decrease in urinary melatonin levels (p < 0.05), serum Cu/Zn SOD (p < 0.001) along with significant increase in serum oxidized LDL (p < 0.001), serum malondialdeheyde (p < 0.01) were observed in patients compared to controls.

Conclusion

Our observations indicate that a decreased excretion of 6-Sulfatoxymelatonin may be causally related to a decrease in serum Cu/Zn SOD, an antioxidant, with a consequent increase in serum oxidized LDL, malondialdehyde contributing to the occurrence of the disease.

Introduction

Melatonin, N-Acetyl-5-Methoxy tryptamine, an exclusive pineal secretion though concerned mainly with circadian rhythm has been recently found to possess a number of other physiological functions including prominent antioxidant activity [1]. Several studies have indicated that acute coronary disease appears either during the early morning hours or in the night in keeping with changes in melatonin secretion levels, suggesting a relationship between melatonin and the disease. Additionally, nocturnal synthesis of melatonin was reported to be low in patients of myocardial infarction [2].

Oxidized LDL, the main product of reactive oxygen species (ROS) such as superoxide anion and hydroxyl radical, has been established to play a major role in the causation of atherosclerosis and coronary artery disease (CAD) [3]. In the oxidation of LDL, initially, conjugated dienes are formed leading to production of malondialdehyde (MDA) [4]. In this process natural antioxidants, Vitamin E carried by LDL along with β-Carotene [5], are however consumed.

Melatonin is a lypophylic substance diffusing freely through the cell membrane and was reported to be a good scavenger of hydroxyl radical which is the most potent amongst ROS [6]. Most of the circulating melatonin is metabolized in the liver to 6-Hydroxymelatonin and subsequently to 6-Sulfatoxymelatonin which is excreted in urine [7], [8]. In states of melatonin deficiency, excessive oxidation of LDL by ROS may occur increasing the risk of atherosclerotic process. Furthermore, an association between oxidation of LDL and decrease in Cu/Zn superoxide dismutase (Cu/Zn SOD) was also observed in CAD [9]. Although melatonin was observed to stimulate Cu/Zn SOD [10], [11], not many studies on concurrent measurement of melatonin or its metabolite together with Cu/Zn SOD activity in patients of CAD including unstable angina are reported. In this study we report a simultaneous measurement of melatonin and Cu/Zn SOD activity along with oxidized LDL and malondialdehyde and we found a decrease in Cu/Zn SOD concurrent with a decrease in urinary melatonin (6-Sulfatoxymelatonin).

Section snippets

Materials and methods

Patients were selected from those admitted in CARE Hospital, Nampally, Hyderabad who fulfilled all inclusion and exclusion criteria. The study group consisted of 21 subjects (16 males and 5 females: mean age 54 ± 7 years) with unstable angina and 30 normal healthy volunteers (19 males and 11 females: mean age 52 ± 9 years) free of acute coronary syndrome. All subjects had given written consent to be included in the study which was approved by the ethical committee. Unstable angina patients were

Statistics

The findings were expressed as Mean ± S.D. Statistical analysis was undertaken using Student's t test. A p-value < 0.05 was accepted statistically significant. Statistical analysis was performed using MINITAB 13 for Windows XP.

Results

The values of urinary melatonin and Cu/Zn SOD in serum as presented in Table 1 were found to be significantly lower in patients in comparison to controls. The levels of serum MDA and Oxidized LDL in patients were found to be significantly higher along with the reduced activity of Cu/Zn SOD. It is evident from the result that there is no significant difference in lipid profile of patients and controls.

Discussion

During the last decade, several important functions of melatonin, other than its role in circadian rhythm, like age related changes, vascular biology, sexual activity and in metabolic effects such as alterations in lipid status and obesity were increasingly observed [1]. Melatonin exerts intracellular effects by virtue of lyophylic nature and also mediated through its specific receptors MT1 and MT2 [13]. The role of melatonin has a direct neutralizing effect on the powerful hydroxyl radical [6]

Acknowledgements

BKSS acknowledges research support received from CARE Foundation, Hyderabad. The authors acknowledge Prof. B. Sadasivudu for his continuous encouragement and critical reading of the manuscript, Dr. Animesh Bardoloi and Department of Laboratory Medicine, CARE Hospital, Banjara Hills, Hyderabad, for support received during the course of this work.

The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology [16].

References (16)

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