Salimi Ahmad, Vaghar-Moussavi Mehrdad, Seydi Enayatollah, Pourahmad Jalal
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Shahid Beheshti University of Medical Sciences, P.O. Box: 14155-6153, Tehran, Iran.
Department of Pharmacology and Toxicology, School of Pharmacy, Ardabil University of Medical Science, Ardabil, Iran.
Environ Sci Pollut Res Int. 2016 May;23(9):8556-64. doi: 10.1007/s11356-016-6090-x. Epub 2016 Jan 22.
Methyl tertiary-butyl ether (MTBE) is a synthetic solvent widely used as oxygenate in unleaded gasoline. Few studies have addressed the cellular toxicity of MTBE on some cell lines, and so far, no comprehensive study has been conducted to investigate the probable immunotoxicity of this compound. In this study, the toxicity of MTBE on human blood lymphocytes was evaluated. Blood lymphocytes were isolated from healthy male volunteers' blood, using Ficoll polysaccharide followed by gradient centrifugation. Cell viability, reactive oxygen species (ROS) formation, lipid peroxidation, glutathione levels, and damage to mitochondria and lysosome were determined in blood lymphocytes after 6-h incubation with different concentrations of MTBE (0.1, 0.5, 1, and 2 mM). Our results showed that MTBE, in particular, decreased cell viability, which was associated with significant increase at intracellular ROS level and toxic alterations in mitochondria and lysosomes in human blood lymphocytes. Moreover, it was shown that MTBE strongly provoked lipid peroxidation and also depleted glutathione level at higher concentrations. Interestingly, MTBE exhibited its cytotoxic effects at low concentrations that may resemble to its concentrations in human blood following occupational and environmental exposure. It is therefore concluded that MTBE was capable of inducing oxidative stress and damage to mitochondria and lysosomes in human lymphocytes at concentrations ranging from 5 to 40 μg/L, which may be present in human blood as a result of environmental exposure.
甲基叔丁基醚(MTBE)是一种合成溶剂,在无铅汽油中广泛用作含氧添加剂。很少有研究探讨MTBE对某些细胞系的细胞毒性,而且到目前为止,尚未进行全面研究来调查该化合物可能的免疫毒性。在本研究中,评估了MTBE对人血淋巴细胞的毒性。使用Ficoll多糖并通过梯度离心从健康男性志愿者的血液中分离出血淋巴细胞。在与不同浓度的MTBE(0.1、0.5、1和2 mM)孵育6小时后,测定血淋巴细胞中的细胞活力、活性氧(ROS)形成、脂质过氧化、谷胱甘肽水平以及线粒体和溶酶体的损伤情况。我们的结果表明,MTBE尤其会降低细胞活力,这与细胞内ROS水平的显著升高以及人血淋巴细胞中线粒体和溶酶体的毒性改变有关。此外,结果显示MTBE在较高浓度下会强烈引发脂质过氧化并消耗谷胱甘肽水平。有趣的是,MTBE在低浓度下就表现出细胞毒性作用,这些低浓度可能类似于职业和环境暴露后人血中的浓度。因此得出结论,MTBE能够在5至40μg/L的浓度范围内诱导人淋巴细胞中的氧化应激以及对线粒体和溶酶体的损伤,而环境暴露可能导致这些浓度存在于人体血液中。