The pineal secretory product melatonin (chemically, N-acetyl-5-methoxytryptamine) acts as an effective antioxidant and free-radical scavenger and plays an important role in several physiological functions such as sleep induction, immunomodulation, cardiovascular protection, thermoregulation, neuroprotection, tumor-suppression and oncostasis. Membrane lipid-peroxidation in terms of malondialdehyde (MDA) and intracellular glutathione (GSH) is considered to be a reliable marker of oxidative stress. The present work was undertaken to study the modulating effect of melatonin on MDA and GSH in human erythrocytes during day and night. Our observation shows the modulation of these two biomarkers by melatonin, and this may have important therapeutic implications. In vitro dose-dependent effect of melatonin also showed variation during day and night. We explain our observations on the basis of melatonin's antioxidative function and its effect on the fluidity of plasma membrane of red blood cells. Rhythmic modulation of MDA and GSH contents emphasized the role of melatonin as an antioxidant and its function against oxidative stress. 1. Introduction Oxidative stress, or the imbalance between oxidant production and antioxidant levels, appears to be favour of the former, consequently resulting in acceleration of neurodegeneration, cognitive impairment, immunosuppression, and ageing [1]. Melatonin (N-acetyl-5-methoxytryptamine) has been known for a long time as the major hormone produced by the pineal gland, but later, it has emerged as a compound that can also be synthesized in other organs and tissues and serves as an autacoid factor. Pineal melatonin is involved in many physiological functions, among them sleep promotion, circadian regulation, immunomodulation, neuroprotection, and tumour suppression. This pineal indoleamine exhibits characteristic diurnal rhythm of synthesis and secretion, which attains its peak at night followed by a gradual decrease during the daytime. In addition, pharmacological doses of melatonin effectively reduce oxidative stress through a number of mechanisms [2]. Melatonin scavenges hydrochlorous acid, detoxifies highly toxic hydroxyl and peroxyl radicals in vitro and scavenges peroxynitrite. It has also been reported to increase the synthesis of glutathione and of several antioxidant enzymes [3]. Upon metabolism, melatonin converts to a number of antioxidant compounds such as, N1-acetyl-N2-formyl-5-methoxy-kynuramine and N1-acetyl-5-methoxy-kynuramine [4]. Therefore, melatonin is considered to be a broad-spectrum antioxidant. It was
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