Departamento de Toxicología y Farmacología, Facultad de Veterinaria, Universidad Complutense de Madrid, Madrid, Spain.
J Pineal Res. 2014 May;56(4):343-70. doi: 10.1111/jpi.12132. Epub 2014 Apr 5.
Metal exposure is associated with several toxic effects; herein, we review the toxicity mechanisms of cadmium, mercury, arsenic, lead, aluminum, chromium, iron, copper, nickel, cobalt, vanadium, and molybdenum as these processes relate to free radical generation. Free radicals can be generated in cells due to a wide variety of exogenous and endogenous processes, causing modifications in DNA bases, enhancing lipid peroxidation, and altering calcium and sulfhydryl homeostasis. Melatonin, an ubiquitous and pleiotropic molecule, exerts efficient protection against oxidative stress and ameliorates oxidative/nitrosative damage by a variety of mechanisms. Also, melatonin has a chelating property which may contribute in reducing metal-induced toxicity as we postulate here. The aim of this review was to highlight the protective role of melatonin in counteracting metal-induced free radical generation. Understanding the physicochemical insights of melatonin related to the free radical scavenging activity and the stimulation of antioxidative enzymes is of critical importance for the development of novel therapeutic strategies against the toxic action of these metals.
金属暴露与多种毒性作用有关;在此,我们综述了镉、汞、砷、铅、铝、铬、铁、铜、镍、钴、钒和钼的毒性机制,这些机制与自由基的生成有关。自由基可以由于各种外源和内源过程在细胞中产生,导致 DNA 碱基的修饰、脂质过氧化的增强以及钙和巯基稳态的改变。褪黑素作为一种普遍存在的多功能分子,通过多种机制发挥有效的抗氧化应激保护作用,并改善氧化/硝化损伤。此外,褪黑素具有螯合特性,这可能有助于减轻我们在这里假设的金属诱导的毒性。本综述的目的是强调褪黑素在对抗金属诱导的自由基生成中的保护作用。理解褪黑素与自由基清除活性和抗氧化酶刺激相关的物理化学见解对于开发针对这些金属的毒性作用的新型治疗策略至关重要。