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Sulfur mustard and respiratory diseases

机译:硫芥菜和呼吸系统疾病

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Victims exposed to sulfur mustard (HD) in World War I and IranIraq war, and those suffered occupational or accidental exposure have endured discomfort in the respiratory system at early stages after exposure, and marked general physical deterioration at late stages due to pulmonary fibrosis, bronchiolitis obliterans or lung cancer. At molecule levels, significant changes of cytokines and chemokines in bronchoalveolar lavage and serum, and of selectins (in particular sE-selectin) and soluble Fas ligand in the serum have been reported in recent studies of patients exposed to HD in IranIraq war, suggesting that these molecules may be associated with the pathophysiological development of pulmonary diseases. Experimental studies in rodents have revealed that reactive oxygen and nitrogen species, their product peroxynitrite (ONOO -), nitric oxide synthase, glutathione, poly (adenosine diphosphate-ribose) polymerase, activating protein-1 signaling pathway are promising drug targets for preventing HD-induced toxicity, whereas N-acetyl cysteine, tocopherols, melatonin, aprotinin and many other molecules have been proved to be effective in prevention of HD-induced damage to the respiratory system in different animal models. In this paper, we will systemically review clinical and pathophysiological changes of respiratory system in victims exposed to HD in the last century, update clinicians and researchers on the mechanism of HD-induced acute and chronic lung damages, and on the relevant drug targets for future development of antidotes for HD. Further research directions will also be proposed.
机译:第一次世界大战和伊朗伊拉克战争中暴露于硫芥末(HD)的受害者以及遭受职业或意外暴露的受害者在暴露后的早期阶段就忍受了呼吸系统的不适,并且由于肺纤维化,细支气管炎而在后期出现了一般的身体恶化闭塞性或肺癌。在分子水平上,最近对伊朗伊拉克战争中暴露于高清的患者进行的研究表明,支气管肺泡灌洗液和血清中的细胞因子和趋化因子以及血清中选择素(特别是sE-选择素)和可溶性Fas配体的显着变化已被报道。这些分子可能与肺部疾病的病理生理发展有关。在啮齿动物上进行的实验研究表明,活性氧和氮物种,其产物过氧亚硝酸盐(ONOO-),一氧化氮合酶,谷胱甘肽,聚腺苷二磷酸核糖聚合酶,激活蛋白1信号通路是有望预防HD- N-乙酰半胱氨酸,生育酚,褪黑激素,抑肽酶和许多其他分子已被证明可有效预防HD诱导的不同动物模型对呼吸系统的损害。在本文中,我们将系统地回顾上个世纪暴露于HD的受害者的呼吸系统的临床和病理生理变化,向临床医生和研究人员介绍HD引起的急性和慢性肺损伤的机制以及未来的相关药物靶标。开发高清解毒剂。还将提出进一步的研究方向。

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