Melatonin: Action as antioxidant and potential applications in human disease and aging

Toxicology, Год журнала: 2010, Номер 278(1), С. 55 - 67

Опубликована: Апрель 26, 2010

Язык: Английский

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Potential role of tryptophan derivatives in stress responses characterized by the generation of reactive oxygen and nitrogen species

Journal of Pineal Research, Год журнала: 2008, Номер 45(3), С. 235 - 246

Опубликована: Март 14, 2008

To face physicochemical and biological stresses, living organisms evolved endogenous chemical responses based on gas exchange with the atmosphere formation of nitric oxide (NO(*)) oxygen derivatives. The combination these species generates a complex network variable extension in space time, characterized by nature level reactive (ROS) nitrogen (RNS) their organic inorganic scavengers. Among latter, this review focusses natural 3-substituted indolic structures. Tryptophan-derived indoles are unsensitive to NO(*), superoxide anion (O(2)(*-)), but react directly other ROS/RNS giving various derivatives, most which have been characterized. Though detection some products like kynurenine nitroderivatives can be performed vitro vivo, it is more difficult for others, e.g., 1-nitroso-indolic compounds. In studies only reveal strong likelihood vivo generation effects sign transient formation. Knowing that 1-nitrosoindoles NO donors nitrosating agents indicating they thus act both as mutagens protectors, necessity thorough evaluation indole-containing drugs accordance oxidative stress given pathology highlighted.

Язык: Английский

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Melatonin and its metabolites vs oxidative stress: From individual actions to collective protection

Journal of Pineal Research, Год журнала: 2018, Номер 65(1)

Опубликована: Июнь 11, 2018

Abstract Oxidative stress (OS) represents a threat to the chemical integrity of biomolecules including lipids, proteins, and DNA. The associated molecular damage frequently results in serious health issues, which justifies our concern about this phenomenon. In addition enzymatic defense mechanisms, there are compounds (usually referred as antioxidants) that offer protection against oxidative events. Among them, melatonin its metabolites constitute particularly efficient family. They OS individual entities through wide variety mechanisms electron transfer, hydrogen radical adduct formation, metal chelation, by repairing biological targets. fact, many them can be classified multipurpose antioxidants. However, what seems unique melatonin's family is their collective effects. Because members metabolically related, most expected present living organisms wherever produced. Therefore, exerted may viewed result combined antioxidant effects parent molecule metabolites. Melatonin's rather exceptional regard, offering versatile OS. It certainly one best nature's defenses damage.

Язык: Английский

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Computational strategies for predicting free radical scavengers' protection against oxidative stress: Where are we and what might follow?

International Journal of Quantum Chemistry, Год журнала: 2018, Номер 119(2)

Опубликована: Май 20, 2018

Abstract Oxidative stress, which is frequently induced by an overproduction of free radicals (FR), poses a high risk to human health. Thus, finding efficient strategies for scavenging FR research area current interest. Among many other aspects, this involves identifying chemical compounds capable offering antioxidant protection (AOP) and quantifying such protection. This review summarizes different computational approaches that can contribute gain deeper knowledge on subject. Several reaction mechanisms may AOP are discussed, as well some key factors influencing their relative importance including the nature reacting FR, polarity environment pH in aqueous solution. Kinetics‐based analyses characterize antioxidants, through activity, presented. Trends from data currently available literature provided. Some regarding AOP, still deserves further investigation, discussed.

Язык: Английский

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Evolutionary formation of melatonin and vitamin D in early life forms: insects take centre stage

Biological reviews/Biological reviews of the Cambridge Philosophical Society, Год журнала: 2024, Номер 99(5), С. 1772 - 1790

Опубликована: Апрель 30, 2024

Melatonin, a product of tryptophan metabolism via serotonin, is molecule with an indole backbone that widely produced by bacteria, unicellular eukaryotic organisms, plants, fungi and all animal taxa. Aside from its role in the regulation circadian rhythms, it has diverse biological actions including cytoprotective responses other functions crucial for survival across different species. The latter properties are also shared metabolites kynuric products generated reactive oxygen species or phototransfomation induced ultraviolet radiation. Vitamins D related photoproducts originate phototransformation ∆5,7 sterols, which 7-dehydrocholesterol ergosterol examples. Their bonds B ring absorb solar radiation [290-315 nm, (UVB) radiation] resulting opening to produce previtamin D, referred as secosteroid. Once formed, can either undergo thermal-induced isomerization vitamin UVB be transformed into lumisterol tachysterol. Vitamin well tachysterol, hydroxylated cyochrome P450 (CYP) enzymes biologically active hydroxyderivatives. best known these 1,25-dihydroxyvitamin (1,25(OH)

Язык: Английский

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Melatonin in the treatment of cancer: a systematic review of randomized controlled trials and meta‐analysis

Journal of Pineal Research, Год журнала: 2005, Номер 39(4), С. 360 - 366

Опубликована: Июль 18, 2005

Abstract: Most observational studies show an association between melatonin and cancer in humans. We conducted a systematic review of randomized controlled trials (RCTs) solid tumor patients its effect on survival at 1 yr. With the aid information specialist, we searched 10 electronic databases from inception to October 2004. included using as either sole treatment or adjunct treatment. Prespecified criteria guided our assessment trial quality. meta‐analysis random effects model. RCTs published 1992 2003 643 patients. All cancers. were same hospital network, unblinded. Melatonin reduced risk death yr (relative risk: 0.66, 95% confidence interval: 0.59–0.73, I 2 = 0%, heterogeneity P ≤ 0.56). Effects consistent across dose, type cancer. No severe adverse events reported. The substantial reduction death, low reported costs related this intervention suggest great potential for treating Confirming efficacy safety will require completion blinded, independently RCTs.

Язык: Английский

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History and development of radiation-protective agents

International Journal of Radiation Biology, Год журнала: 2009, Номер 85(7), С. 539 - 573

Опубликована: Янв. 1, 2009

Purpose: The search for ideal protective agents use in a variety of radiation scenarios has continued more than six decades. This review evaluates and procedures that have the potential to protect against acute late effects ionising when administered either before or after exposure.Conclusion: Over years, extensive experimental studies radiation-protective enhanced our knowledge physics, chemistry, biology. However, translation from animal testing various scenarios, such as prophylactic adjuncts radiotherapy post-exposure treatments victims accidents/incidents, been slow. Nevertheless, number compounds are now available situations. These include approved by U.S. Food Drug Administration reducing exposure internal radionuclides (Prussian blue, calcium diethylenetriamene pentaacetate (DTPA) zinc DTPA, potassium iodide) amifostine alleviating xerostomia associated with radiotherapy. Consensus groups also recommended other therapies granulocyte colony-stimulating factor radiation-induced neutropenia. therapeutic research pipeline includes those naturally-occurring low toxicity, provide long window protection, normal tissue while sensitising tumours, act via receptors modulate biological processes induction genes responsible radioresistance. injury will undoubtedly continue into future influence areas research.

Язык: Английский

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AFMK, a melatonin metabolite, attenuates X‐ray‐induced oxidative damage to DNA, proteins and lipids in mice

Journal of Pineal Research, Год журнала: 2007, Номер 42(4), С. 386 - 393

Опубликована: Март 29, 2007

Antioxidant function of melatonin is well established. However, N(1)-acetyl-N(2)-formyl-5-methoxykynuramine (AFMK), a metabolite sparingly investigated biogenic amine, especially in relation to its vivo antioxidant function. We have evaluated the oxidative damage biomolecules (DNA, protein and lipid) induced by X-irradiation C57BL mice prophylactic action AFMK. The extent DNA was analyzed single-cell gel electrophoresis cerebral cortex serum 8-hydroxydeoxyguanosine (8-OHdG) levels enzyme-linked immunosorbent assay. Oxidative modification lipid measured terms carbonyl content 4-HAE + MDA (4-hydroxyalkenal malondialdehyde) status brain cortex. Radiation exposure dramatically augmented level 8-OHdG as migration comet tail. AFMK pretreatment significantly inhibited damage. In addition, radiation-induced augmentation HAE ameliorated pretreatment. Whole-body also reduced sulfhydryl contents (protein-bound sulfhydryl, total nonprotein sulfhydryl) which were protected Radiation-induced decline capacity plasma reversed pretreated mice. Moreover, showed very high vitro hydroxyl radical scavenging potential an electron spin resonance (ESR) study 2-hydroxy-5,5-dimethyl-1-pyrrolineN-oxide (DMPO-OH) adduct. IC(50) values resulting from ESR analysis 338.08 nm. present indicate that potent both systems.

Язык: Английский

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Melatonin: therapeutic and clinical utilization

International Journal of Clinical Practice, Год журнала: 2007, Номер 61(5), С. 835 - 845

Опубликована: Фев. 13, 2007

Melatonin, acting through melatonin receptors, is involved in numerous physiological processes including circadian entrainment, blood pressure regulation, oncogenesis, retinal physiology, seasonal reproduction, ovarian immune function and most recently inducing osteoblast differentiation. Moreover, was proved to be a potent-free radical scavenger broad-spectrum antioxidant. More research required into the effects of therapeutically modulating melatoninergic system on haemodynamics rhythm under varying physiopathological conditions possible impact morbidity mortality humans.

Язык: Английский

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Therapeutic Actions of Melatonin in Cancer: Possible Mechanisms

Integrative Cancer Therapies, Год журнала: 2008, Номер 7(3), С. 189 - 203

Опубликована: Сен. 1, 2008

Melatonin is a phylogenetically well-preserved molecule with diverse physiological functions. In addition to its well-known regulatory control of the sleep/wake cycle, as well circadian rhythms generally, melatonin involved in immunomodulation, hematopoiesis, and antioxidative processes. Recent human animal studies have now shown that also has important oncostatic properties. Both at pharmacological doses exerts growth inhibitory effects on breast cancer cell lines. hepatomas, through activation MT1 MT2 receptors, inhibits linoleic acid uptake, thereby preventing formation mitogenic metabolite 1,3-hydroxyoctadecadienoic acid. model studies, been preventative action against nitrosodiethylamine (NDEA)-induced liver cancer. prostate tumors via receptors inducing translocation androgen receptor cytoplasm inhibition effect endogenous androgens. There abundant evidence indicating tumor initiation, promotion, progression. The anticarcinogenic neoplastic cells relies antioxidant, immunostimulating, apoptotic Melatonin's actions include direct augmentation natural killer (NK) activity, which increases immunosurveillance, stimulation cytokine production, for example, interleukin (IL)-2, IL-6, IL-12, interferon (IFN)-gamma. action, protects hematopoietic precursors from toxic anticancer chemotherapeutic drugs. secretion impaired patients suffering cancer, endometrial or colorectal increased incidence seen nurses other night shift workers suggests possible link between diminished exposure light during nighttime. surge thus considered "natural restraint"

Язык: Английский

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