Flora S J S, Shrivastava Rupal, Mittal Megha
Division of Regulatory Toxicology, Defence Research and Development, Establishment, Jhansi Road, Gwalior, M.P. 474 002, India.
Curr Med Chem. 2013;20(36):4540-74. doi: 10.2174/09298673113209990146.
Heavy metals are known to cause oxidative deterioration of bio-molecules by initiating free radical mediated chain reaction resulting in lipid per-oxidation, protein oxidation and oxidation of nucleic acid like DNA and RNA. The development of effective dual functioning antioxidants, possessing both metal-chelating and free radical-scavenging properties should bring into play. Administration of natural and synthetic antioxidants like, quercetin, catechin, taurine, captopril, gallic acid, melatonin, N-acetyl cysteine, α- lipoic acid and others have been recognized in the disease prevention and clinical recovery against heavy metal intoxication. These antioxidants affect biological systems not only through direct quenching of free radicals but also via chelation of toxic metal(s). These antioxidants also, have the capacity to enhance cellular antioxidant defense mechanism by regenerating endogenous antioxidants, such as glutathione and vitamin C and E. They also influence cellular signaling and trigger redox sensitive regulatory pathways. The reactivity of antioxidants in protecting against heavy metal induced oxidative stress depends upon their structural properties, their partitioning abilities between hydrophilic and lipophilic environment and their hydrogen donation antioxidant properties. Herein, we review the structural, biochemical and pharmacological properties of selected antioxidants with particular reference to their ability to (i) chelate heavy metals from its complex (ii) ameliorate free radical (iii) terminate heavy metal induced free radical chain reaction (iv) regenerate endogenous antioxidants and, (v) excretion of metal without its redistribution.
众所周知,重金属会引发自由基介导的链式反应,导致生物分子发生氧化降解,进而造成脂质过氧化、蛋白质氧化以及DNA和RNA等核酸氧化。因此,开发兼具金属螯合和自由基清除特性的高效双功能抗氧化剂具有重要意义。天然和合成抗氧化剂,如槲皮素、儿茶素、牛磺酸、卡托普利、没食子酸、褪黑素、N - 乙酰半胱氨酸、α - 硫辛酸等,在预防疾病和临床治疗重金属中毒恢复方面已得到认可。这些抗氧化剂不仅通过直接淬灭自由基影响生物系统,还通过螯合有毒金属发挥作用。此外,这些抗氧化剂能够通过再生内源性抗氧化剂,如谷胱甘肽、维生素C和E,增强细胞抗氧化防御机制。它们还会影响细胞信号传导并触发氧化还原敏感的调节途径。抗氧化剂在抵御重金属诱导的氧化应激中的反应性取决于其结构特性、在亲水和亲脂环境之间的分配能力以及氢供体抗氧化特性。在此,我们综述了所选抗氧化剂的结构、生化和药理特性,特别提及它们(i)从复合物中螯合重金属(ii)改善自由基(iii)终止重金属诱导的自由基链式反应(iv)再生内源性抗氧化剂以及(v)在不发生金属重新分布的情况下排出金属的能力。