Nourani Mohammad Reza, Azimzadeh Sadegh, Ghanei Mostafa, Imani Fooladi Abbas Ali
Chemical Injuries Research Center and.
J Recept Signal Transduct Res. 2014 Apr;34(2):125-30. doi: 10.3109/10799893.2013.864677. Epub 2013 Dec 17.
Sulfur mustard (SM) is an alkylating agent identified as a potent chemical warfare agent. More recently, SM was used in the Iraq conflict against Iranian troops and civilians. At present, there are many people suffering from chronic obstructive pulmonary disease (COPD) due to mustard gas in Iran. SM increases the endogenous production of reactive oxygen species (ROS). The oxidant/antioxidant imbalance present in the lungs of these patients also results from the impaired capacity of the antioxidant/detoxification enzymes to detoxify the harmful reactive oxygen metabolites.
One of the major antioxidants in human airways is glutathione S-transferase. They facilitate the detoxification of various environmental of oxidative stress. In this study, we attempted to understand the significance different in expression of GSTs in airway wall of chemical patients and control.
Seven normal and 20 SM induced COPD individuals were studied. Bronchoscopy was performed in all subjects and two specimens were taken from the main bronchus for mRNA extraction, PCR analysis and immunohistochemistry.
SM-induced COPD individuals showed expression of GSTA1 2.51 ± 0.83-, GSTM1 2.84 ± 1.71- and GSTP1 5.61 ± 2.59-folds higher than those of controls that revealed. GSTP1-immunoreactivity was strongly expressed in luminal border of normal samples. SM patient samples immunoreactivity for GSTP1 in the same area were negative.
According to these findings, we speculated that overexpression of GSTs mRNA in patients revealed that GSTs plays an important role in cellular protection against oxidative stress of MS in airway wall of patients.
硫芥(SM)是一种烷基化剂,被确定为一种强力化学战剂。最近,硫芥在伊拉克冲突中被用于对付伊朗军队和平民。目前,伊朗有许多人因芥子气而患有慢性阻塞性肺疾病(COPD)。硫芥会增加活性氧(ROS)的内源性产生。这些患者肺部存在的氧化/抗氧化失衡也是由于抗氧化/解毒酶解毒有害活性氧代谢产物的能力受损所致。
人类气道中的主要抗氧化剂之一是谷胱甘肽S-转移酶。它们有助于对各种环境氧化应激进行解毒。在本研究中,我们试图了解化学中毒患者和对照组气道壁中谷胱甘肽S-转移酶(GSTs)表达差异的意义。
研究了7名正常人和20名硫芥诱导的慢性阻塞性肺疾病患者。对所有受试者进行支气管镜检查,并从主支气管采集两个样本用于mRNA提取、PCR分析和免疫组织化学。
硫芥诱导的慢性阻塞性肺疾病患者显示,GSTA1的表达比对照组高2.51±0.83倍,GSTM1高2.84±1.71倍,GSTP1高5.61±2.59倍。GSTP1免疫反应性在正常样本的管腔边界强烈表达。硫芥患者样本在同一区域对GSTP1的免疫反应性为阴性。
根据这些发现,我们推测患者中GSTs mRNA的过度表达表明,GSTs在患者气道壁中对硫芥氧化应激的细胞保护中起重要作用。