Acute Gene Expression Profile of Lung Tissue Following Sulfur Mustard Inhalation Exposure in Large Anesthetized Swine.

التفاصيل البيبلوغرافية
العنوان:	Acute Gene Expression Profile of Lung Tissue Following Sulfur Mustard Inhalation Exposure in Large Anesthetized Swine.
المؤلفون:	Jugg BJ; CBR Division, Dstl Porton Down , Salisbury, Wiltshire SP4 0JQ, U.K., Hoard-Fruchey H; US Army Medical Research Institute of Chemical Defense , 2900 Ricketts Point Road, Aberdeen Proving Ground, Maryland 21010, United States., Rothwell C; US Army Medical Research Institute of Chemical Defense , 2900 Ricketts Point Road, Aberdeen Proving Ground, Maryland 21010, United States., Dillman JF; US Army Medical Research Institute of Chemical Defense , 2900 Ricketts Point Road, Aberdeen Proving Ground, Maryland 21010, United States., David J; CBR Division, Dstl Porton Down , Salisbury, Wiltshire SP4 0JQ, U.K., Jenner J; CBR Division, Dstl Porton Down , Salisbury, Wiltshire SP4 0JQ, U.K., Sciuto AM; US Army Medical Research Institute of Chemical Defense , 2900 Ricketts Point Road, Aberdeen Proving Ground, Maryland 21010, United States.
المصدر:	Chemical research in toxicology [Chem Res Toxicol] 2016 Oct 17; Vol. 29 (10), pp. 1602-1610. Date of Electronic Publication: 2016 Sep 12.
نوع المنشور:	Journal Article; Research Support, U.S. Gov't, Non-P.H.S.
اللغة:	English
بيانات الدورية:	Publisher: American Chemical Society Country of Publication: United States NLM ID: 8807448 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1520-5010 (Electronic) Linking ISSN: 0893228X NLM ISO Abbreviation: Chem Res Toxicol Subsets: MEDLINE
أسماء مطبوعة:	Publication: Washington Dc : American Chemical Society Original Publication: Washington, DC : American Chemical Society, c1988-
مواضيع طبية MeSH:	Anesthesia* , Gene Expression Profiling, Lung/drug effects , Lung/metabolism , Mustard Gas/administration & dosage , Mustard Gas/*toxicity, Acetylcysteine/therapeutic use ; Administration, Inhalation ; Animals ; Dose-Response Relationship, Drug ; Female ; Inhalation Exposure ; Models, Animal ; Swine ; Toxicity Tests
مستخلص:	Sulfur mustard (HD) is a vesicating and alkylating agent widely used on the battlefield during World War I and more recently in the Iran-Iraq War. It targets the eyes, skin, and lungs, producing skin burns, conjunctivitis, and compromised respiratory function; early acute effects lead to long-term consequences. However, it is the effects on the lungs that drive morbidity and eventual mortality. The temporal postexposure response to HD within lung tissue raises the question of whether toxicity is driven by the alkylating properties of HD on critical homeostatic pathways. We have established an anesthetized swine model of inhaled HD vapor exposure to investigate the toxic effects of HD 12 h postexposure. Large white female swine were anesthetized and instrumented prior to exposure to air, 60 (sublethal) or 100 μg·kg ^-1 (∼LD 40 ) doses of HD (10 min). Physiological parameters were continuously assessed. Data indicate that exposure to 100 μg·kg ^-1 HD lowered arterial blood oxygenation and increased shunt fraction and lavage protein compared with those of air-exposed controls and the 60 μg·kg ^-1 dose of HD. Histopathology showed an increased total pathology score between the 100 μg·kg ^-1 HD group and air-exposed controls. Principal component analysis of differentially expressed genes demonstrated a distinct and separable response of inhaled HD between air-exposed controls and the 60 and 100 μg·kg ^-1 doses of HD. Canonical pathway analysis demonstrated changes in acute phase response signaling, aryl hydrocarbon receptor signaling, NRF-2 mediated oxidative stress, and zymosterol biosynthesis in the 60 and 100 μg·kg ^-1 HD dose group. Transcriptional changes also indicated alterations in immune response, cancer, and cell signaling and metabolism canonical pathways. The 100 μg·kg ^-1 dose group also showed significant changes in cholesterol biosynthesis. Taken together, exposure to inhaled HD had a significant effect on physiological responses coinciding with acute changes in gene expression and lung histopathology. In addition, transcriptomics support the observed beneficial effects of N-acetyl-l-cysteine for treatment of acute inhalation HD exposure.
المشرفين على المادة:	T8KEC9FH9P (Mustard Gas) WYQ7N0BPYC (Acetylcysteine)
تواريخ الأحداث:	Date Created: 20160913 Date Completed: 20171009 Latest Revision: 20180125
رمز التحديث:	20221213
DOI:	10.1021/acs.chemrestox.6b00069
PMID:	27617619
قاعدة البيانات:	MEDLINE

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تدمد:	1520-5010
DOI:	10.1021/acs.chemrestox.6b00069