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有机硒化合物作为潜在的治疗和化学预防剂:综述

Organoselenium compounds as potential therapeutic and chemopreventive agents: a review.

作者信息

Soriano-Garcia M

机构信息

Departamento de Bioquímica, Instituto de Química, Universidad Nacional Autónoma de México, Mexico D.F., Mexico.

出版信息

Curr Med Chem. 2004 Jun;11(12):1657-69. doi: 10.2174/0929867043365053.

Abstract

Selenium is an essential trace element. It is, however toxic at concentration little above which is required for health. Selenium is incorporated into proteins as selenocysteine, the 21(st) amino acid. Selenoproteins are found in bacteria, archaea and eukaryotes. Biochemical and physicochemical properties of selenium result in the unique redox characteristics of selenocysteine and its use in antioxidant enzymes. In this context of a redox reaction is the reduction of reactive oxygen metabolites by glutathione peroxidases, helping to maintain membrane integrity, reduces the oxidative damage to lipids, lipoproteins, and DNA. Selenium has structural and enzymatic roles. Selenium influences a number of endocrine processes, most notably, those involved in thyroid hormone synthesis and metabolism. Se is needed for the proper functioning of the immune system, a role in viral suppression, AIDS, and also is implicated in delaying the aging process. Its deficiency has been linked to a number of disorders such as heart disease, diabetes, and diseases of the liver, and it is required for sperm motility and may reduce the risk of miscarriage. Se supplementation has recently moved from the realm of correcting nutritional deficiencies to one of pharmacological intervention, especially in the clinical domain of cancer chemoprevention. During the last few years, a tremendous effort has been directed toward the synthesis of stable organoselenium compounds that could be used as antioxidants, enzyme modulators, antitumor, antimicrobials, antihypertensive agents, antivirals and cytokine inducers. The biochemistry and pharmacology of selenium-based compounds are subjects of intense current interest, especially from the point of view of public heath. The purpose of this review is to discuss the recent pharmacological applications of organoselenium compounds as therapeutic agents in the treatment of several diseases.

摘要

硒是一种必需的微量元素。然而,其浓度略高于健康所需水平时就会有毒性。硒以硒代半胱氨酸(第21种氨基酸)的形式掺入蛋白质中。硒蛋白存在于细菌、古细菌和真核生物中。硒的生化和物理化学性质导致了硒代半胱氨酸独特的氧化还原特性及其在抗氧化酶中的应用。在这种氧化还原反应的背景下,谷胱甘肽过氧化物酶可还原活性氧代谢产物,有助于维持膜的完整性,减少对脂质、脂蛋白和DNA的氧化损伤。硒具有结构和酶促作用。硒影响许多内分泌过程,最显著的是那些参与甲状腺激素合成和代谢的过程。免疫系统的正常运作需要硒,它在抑制病毒、治疗艾滋病方面发挥作用,还与延缓衰老过程有关。其缺乏与多种疾病有关,如心脏病、糖尿病和肝脏疾病,精子活力也需要硒,它可能降低流产风险。硒的补充最近已从纠正营养缺乏领域转向药物干预领域,特别是在癌症化学预防的临床领域。在过去几年中,人们付出了巨大努力来合成稳定的有机硒化合物,这些化合物可用作抗氧化剂、酶调节剂、抗肿瘤剂、抗菌剂、抗高血压剂、抗病毒剂和细胞因子诱导剂。基于硒的化合物的生物化学和药理学是当前人们密切关注的课题,特别是从公共卫生的角度来看。这篇综述的目的是讨论有机硒化合物作为治疗剂在治疗几种疾病中的最新药理学应用。

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