Melatonin as an antioxidant: biochemical mechanisms and pathophysiological implications in humans.

Reíter, Russel J.; Tan, Dun Xian; Mayo, Juan C.; Sáinz, Rosa M.; León, Josefa; Czarnocki, Zbigniew

doi:10.18388/abp.2003_3637

Cited by 516 publications

(304 citation statements)

References 108 publications

Supporting

Mentioning

289

Contrasting

Unclassified

Order By: Relevance

“…This was likely due to the rise of the circulating serum levels of melatonin produced by the exogenous administration of its precursor, and indicates that rising serum levels of melatonin are accompanied by a decline in the levels produced by heterophils. This confirms previous studies that have shown melatonin to be a powerful direct free radical scavenger and general antioxidant, which reduces oxidative damage at both physiological and pharmacological concentrations [27]. In earlier studies, a decline in levels and in lipid peroxidation after incubation of heterophils from old animals with the physiological melatonin concentrations found in young animals had been observed [28,29]; furthermore, we observed…”

Section: Discussionsupporting

confidence: 92%

Tryptophan Modulates Cell Viability, Phagocytosis and Oxidative Metabolism in Old Ringdoves

Paredes

Terrón

Marchena

et al. 2007

Basic Clin Pharma Tox

View full text Add to dashboard Cite

The decrease of melatonin with age contributes to immunosenescence. Its restoration via tryptophan may have immuno-enhancing effects. Therefore, we determined the effect of tryptophan administration on circulating serotonin, melatonin, cell viability, phagocytic function and levels of free radical generation of blood heterophils from old ringdoves ( Streptopelia risoria ), aged 11-13 years. The animals received a single oral capsule of  -tryptophan 1 hr after the onset of the light period. The tryptophan treatment significantly increased serum melatonin and serotonin levels, cell viability, phagocytosis index and phagocytosis percentage. Superoxide anion levels decreased significantly with respect to vehicle values, with the nocturnal reduction being greater than that which occurred during the light period. This suggests that orally administered tryptophan at the beginning of the day enhanced heterophil viability, phagocytic response and detoxification of superoxide anion radicals deriving from this immune function, as a result of the immunoregulatory action of melatonin and serotonin.Melatonin ( N -acetyl-5-methoxytryptamine), the main secretory product of the pineal gland, is produced and secreted into the blood in a circadian manner with maximal production occurring during the dark phase of the light-dark cycle. The synthesis and secretion of melatonin act by providing information to the organism about its overall temporal organization and synchronize diurnal and seasonal changes in the immune system [1].There is a gradual decline in the melatonin rhythm as animals age: the amplitude and mean levels of melatonin undergo a significant reduction, known as the 'melatonin deficiency state ' [2]. In addition, stress seems to lower the circulating levels of the indoleamine [3]. As a result, the use of melatonin as a pharmacological agent to prevent the agerelated decline in the immune system function and neutralize the adverse effects of stress has been extensively examined. In this sense, a number of studies support the immunoregulatory action of melatonin [4], with several in vivo and in vitro studies indicating that this indoleamine modulates certain immune functions and attenuates oxidative reactions in both mammals and birds [5,6]. In contrast to the number of studies using melatonin as an immunomodulatory agent, little attention has been paid to the possible effects that melatonin's precursor, the amino acid tryptophan, may exert, after its conversion into melatonin, on the immune system. Thus, it has been previously suggested that in mammals, the oral administration of tryptophan increases the plasma levels of melatonin, leading to an augmented innate immune response [7]. Particularly, the supply with the amino acid seems to stimulate the antigen ingestion of rat macrophages [8].In our previous work with the ringdove ( Streptopelia risoria ), we found a decline in phagocytosis with ageing, due at least in part to the absence of a circadian rhythm of melatonin in these animals; this was accompanied...

show abstract

Section: Discussionsupporting

confidence: 92%

Tryptophan Modulates Cell Viability, Phagocytosis and Oxidative Metabolism in Old Ringdoves

Paredes

Terrón

Marchena

et al. 2007

Basic Clin Pharma Tox

View full text Add to dashboard Cite

show abstract

“…Melatonin promotes the NADPH-dependent GSSG reduction by GRx [37], surpassing the needs for GSH [38], which is consistent with higher GRx activity in the presence of melaxen. The increase in GSH and aMT6s support these observations and indicate that melatonin activity can be connected with the expression of antioxidant enzymes [16]. The decrease in GST activity may be associated with competition of the GPx/GRx system for GSH.…”

Section: Discussionsupporting

confidence: 71%

Effects of Melatonin‐Aided Therapy on the Glutathione Antioxidant System Activity and Liver Protection

Popov

Shulgin

Попова

et al. 2015

J Biochem & Molecular Tox

View full text Add to dashboard Cite

Acute hepatitis results from oxidative stress triggered by hepatotoxic drugs causing liver injury and the activation of caspases cascade. The glutathione antioxidant system protects against reactive oxygen species and mitigates development of these processes. The effectiveness of silymarin, a polyphenolic flavonoid, essenthiale, composed of phosphatidyl choline, and melaxen, a melatonin-correcting drug, as hepatoprotectors has been investigated. The variation of 6-sulfatoxymelatonin (aMT6s), resulting from the biotransformation of melatonin, and GSH has been measured. The activities of caspase-1 and caspase-3, glutathione antioxidant system, and NADPH-generating enzymes were determined. The aMT6s decreases in patients with drug hepatitis and recovers with administration of mexalen. GSH increased in the presence of the studied hepatoprotectors. Pathologically activated caspase-1 and caspase-3 decreased their activities in the presence of hepatoprotectors with melaxen showing the highest effect. The positive effect of melatonin appears to be related to the suppression of decompensation of the glutathione antioxidant system functions, recovery of liver redox status, and the attenuation of inhibition of the NADPH supply.

show abstract

“…A number of physiological and pharmacological effects of melatonin have been considered in relation to its antioxidant activity [31]. The antioxidant effects of melatonin is due to the various complex mechanisms including upregulation of antioxidant and downregulation of pro-oxidant enzymes, suppression of mitochondrial radical formation and free radical scavenging [32].…”

Section: Discussionmentioning

confidence: 99%

Melatonin cytotoxicity in human leukemia cells: relation with its pro‐oxidant effect

Büyükavcı

Özdemir

Buck

et al. 2006

Fundamemntal Clinical Pharma

View full text Add to dashboard Cite

Melatonin has a variety of functions in human physiology and is involved in a number of pathological events including neoplastic processes. The tissue protective actions of melatonin are attributed to its antioxidant activity though, under certain conditions, melatonin might also exert oxidant effects, particularly in cancer cells. This study evaluated the effects of 10(-5) and 10(-3) m concentrations of melatonin on human leukemia cells. Moderate cytotoxic effects of melatonin at 10(-3) m concentrations were observed in CMK, Jurkat and MOLT-4 cells which was associated with significant reactive oxygen species (ROS) generation. Melatonin treatment was not associated with significant cytotoxicity in HL-60 cells, although the generation of ROS was significantly increased. K562 and Daudi cells did not appear to be effected by melatonin treatment. Cellular membrane lipid peroxidation was not influenced by melatonin with the exception of CMK cells. Cell cycle kinetics were not affected in melatonin-treated samples, again with the exception of CMK cells which showed increased apoptosis. Melatonin, therefore, induces the production of ROS that may be associated with cytotoxicity depending on the concentration of melatonin in some leukemia cells and does not appear to stimulate leukemia cell growth. These pro-oxidant actions of melatonin may assist in limiting leukemic cell growth.

show abstract

Melatonin as an antioxidant: biochemical mechanisms and pathophysiological implications in humans.

Cited by 516 publications

References 108 publications

Tryptophan Modulates Cell Viability, Phagocytosis and Oxidative Metabolism in Old Ringdoves

Tryptophan Modulates Cell Viability, Phagocytosis and Oxidative Metabolism in Old Ringdoves

Effects of Melatonin‐Aided Therapy on the Glutathione Antioxidant System Activity and Liver Protection

Melatonin cytotoxicity in human leukemia cells: relation with its pro‐oxidant effect

Contact Info

Product

Resources

About