ROLE OF MELATONIN IN THE BIOLOGICAL EFFECTS OF MAGNETIC FIELDS

褪黑素(N-乙酰-5-甲氧基色胺，MLT)是一种主要在松果体和视网膜合成的吲哚激素，控制着与昼夜节律和季节节律相关的几种基本生理功能。它与免疫反应、衰老过程和与年龄相关的疾病有关。由于所有这些过程都与重要细胞成分的氧化损伤有关，因此人们推测褪黑素可能是一种天然的抗氧化剂和自由基清除剂。进一步的研究表明，电磁场诱导的夜间褪黑激素水平的降低可能是环境电磁场暴露与癌症之间的弱相关性的原因。本研究项目的主要目标是确定MLT与自由基(羟基、甲基、甲氧基)以及与单线态氧(一种高度氧化的氧)反应的速率常数。除了MLT外，我们还研究了相关的吲哚类化合物6-羟基褪黑素、6-氯褪黑素、5-甲氧基色胺、5-羟色胺和色氨酸代谢产物犬尿氨酸。我们发现所有吲哚类化合物都以接近扩散控制的速度与羟基自由基反应。吲哚与甲基自由基的相互作用效率较低。相比之下，清除甲氧基自由基是一个非常快的过程。我们没有发现MLT和超氧化物之间发生反应的证据。单线态氧猝灭效率取决于吲哚基团(S)的位置和性质，也取决于反应环境。褪黑素前体5-羟色胺在铁和过氧化氢存在下产生羟基自由基，褪黑素代谢产物6-羟基褪黑素即使在没有外源添加的过氧化氢的情况下也产生大量的羟基自由基。鉴于MLT的低毒性，其高亲脂性可在所有类型的细胞中蓄积，并通过血液在全身分布，褪黑素在药物剂量下可被认为是一种潜在的抗氧化剂。然而，褪黑激素的生理浓度(血浆中的100 pg/ml)可能太低，无法作为一种生理抗氧化剂。因此，电磁场的生物学效应似乎不太可能通过调节褪黑激素水平来发挥。-褪黑激素、吲哚激素、松果体、视网膜、羟基自由基

Melatonin (N-acetyl-5-methoxytryptamine, MLT), an indole hormone synthesized primarily in the pineal gland and the retina, controls several essential physiological functions associated with circadian and seasonal rhythms. It is involved in immune responses, aging processes and age-related diseases. Because all these process are associated with oxidative damage of vital cell components, it has been postulated that melatonin may function as a natural antioxidant and free radical scavenger. It has further been suggested that EMF-induced decrease in nocturnal levels of melatonin may be responsible for the weak association between environmental EMF exposure and cancer. The primary objective of this research project was to determine rate constants for the reaction of MLT with free radicals (hydroxyl, methyl, methoxyl) and with singlet oxygen a highly oxidizing form of oxygen. In addition to MLT, we studied related indoles 6-hydroxymelatonin, 6-chloromelatonin, 5-methoxytryptamine, 5-hydroxytryptamine, and a tryptophan metabolite kynurenine.We have found that all the indoles react with the hydroxyl radical at near diffusion controlled rates. The interaction of the indoles with methyl radicals is less efficient. In contrast, scavenging of methoxyl radicals is a very fast process. We found no evidence for a reaction between MLT and superoxide. The singlet oxygen quenching efficacy depends on the position and the nature of the substituent(s) of the indole nucleus, and also on the reaction environment. The melatonin precursor serotonin generated hydroxyl radicals in the presence of ferric iron and hydrogen peroxide, and the melatonin metabolite 6-hydroxymelatonin generated copious amounts of hydroxyl radicals even in the absence of exogenously added hydrogen peroxide. Given the reported low toxicity of MLT, its ready accumulation in all types of cells due to its high lipophilicity and distribution throughout the entire body via the blood stream, melatonin may be considered as a potential antioxidant when taken in pharmacological doses. However, the physiological concentrations of melatonin (100 pg/ml in the plasma) are probably too low for the hormone to act as a physiological antioxidant. Thus it seems highly improbable that the biological effects of EMF can be exerted via a modulation of melatonin levels. - melatonin, indole hormone, pineal gland, retina,hydroxyl radicals