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偏亚砷酸钠诱导人红细胞产生活性氧:抗氧化和膜氧化还原系统受损、血红蛋白氧化及形态改变。

Sodium meta-arsenite induced reactive oxygen species in human red blood cells: impaired antioxidant and membrane redox systems, haemoglobin oxidation, and morphological changes.

作者信息

Maheshwari Nikhil, Khan Fahim Halim, Mahmood Riaz

机构信息

a Department of Biochemistry, Faculty of Life Sciences , Aligarh Muslim University , Aligarh , India.

出版信息

Free Radic Res. 2017 May;51(5):483-497. doi: 10.1080/10715762.2017.1327714.

DOI:10.1080/10715762.2017.1327714
PMID:28480809
Abstract

Arsenic (As) is an air and water toxicant that causes cancer in multiple organs. Humans are exposed to As through contaminated water. We have examined the cytotoxicity of sodium meta-arsenite (SA), an As(III) compound, in human red blood cells (RBC) under in vitro conditions. Haemolysates were prepared from human RBC treated with different concentrations of SA (0.1-5.0 mM) for 5 h at 37 °C. SA treatment of RBC caused significant increase in methaemoglobin formation, protein and lipid oxidation, and nitric oxide levels. It also resulted in decrease in glutathione levels, methaemoglobin reductase activity and plasma membrane redox system. SA exposure also inhibited the pathways of glucose metabolism while increasing AMP deaminase and glyoxalase-I. It impaired the enzymatic and non-enzymatic antioxidant defence systems which resulted in decreased antioxidant power and a compromised ability to quench free radicals. SA exposure also damaged the membrane since it decreased the activity of membrane bound enzymes, increased the osmotic fragility of treated cells and induced gross morphological changes. This cytotoxicity was the result of oxidative damage since the production of reactive oxygen species (ROS) was increased in SA treated erythrocytes. Thus As(III) causes extensive damage to RBC which impairs their antioxidant system and alters the major cellular metabolic pathways. All this has the potential to lower the oxygen carrying capacity of RBC and reduce their lifespan in blood.

摘要

砷(As)是一种空气和水污染物,可导致多个器官发生癌症。人类通过受污染的水接触砷。我们在体外条件下研究了亚砷酸钠(SA,一种As(III)化合物)对人红细胞(RBC)的细胞毒性。用不同浓度的SA(0.1 - 5.0 mM)在37°C下处理人RBC 5小时后制备溶血产物。SA处理RBC导致高铁血红蛋白形成、蛋白质和脂质氧化以及一氧化氮水平显著增加。它还导致谷胱甘肽水平、高铁血红蛋白还原酶活性和质膜氧化还原系统降低。SA暴露还抑制了葡萄糖代谢途径,同时增加了AMP脱氨酶和乙二醛酶-I。它损害了酶促和非酶促抗氧化防御系统,导致抗氧化能力下降和清除自由基的能力受损。SA暴露还损害了细胞膜,因为它降低了膜结合酶的活性,增加了处理后细胞的渗透脆性并诱导了明显的形态变化。这种细胞毒性是氧化损伤的结果,因为SA处理的红细胞中活性氧(ROS)的产生增加。因此,As(III)对RBC造成广泛损害,损害其抗氧化系统并改变主要的细胞代谢途径。所有这些都有可能降低RBC的携氧能力并缩短其在血液中的寿命。

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