Administration of nitrite after chlorine gas exposure prevents lung injury: effect of administration modality.
Administration of nitrite after chlorine gas exposure prevents lung injury: effect of administration modality.
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氯气暴露后给予亚硝酸盐可预防肺损伤：给药方式的效果。
DOI：
10.1016/j.freeradbiomed.2012.08.007
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发表时间：
2012
影响因子：
7.4
通讯作者：
Patel,RakeshP
中科院分区：
文献类型：
--
作者：
Samal,AndreyA;Honavar,Jaideep;Brandon,Angela;Bradley,KelleyM;Doran,Stephen;Liu,Yanping;Dunaway,Chad;Steele,Chad;Postlethwait,EdwardM;Squadrito,GiuseppeL;Fanucchi,MichelleV;Matalon,Sadis;Patel,RakeshP
Cl 2气体毒性是复杂的，发生在暴露期间和暴露后，导致急性肺损伤（ALI）和反应性气道综合征（RAS）。此外，氯暴露可能发生在不同的情况下，包括大规模伤亡的情况下，强调需要的exxetamine后治疗，是有效的，并适合快速和容易的管理。在这项研究中，我们评估了大鼠在暴露于Cl 2后30分钟通过腹膜内（ip）或肌肉内（im）注射单剂量亚硝酸盐（1 mg/kg）减少ALI的功效。大鼠暴露于Cl_2气体（400 ppm，30 min）后，肺表面蛋白和多形核细胞（PMNs）的BAL取样显示，ALI和RAS显著增加，乙酰甲胆碱激发前后气道阻力和弹性增加。腹膜内亚硝酸盐降低了BAL蛋白的Cl 2依赖性增加，但不影响PMN。与此相反，IM亚硝酸盐降低BAL PMN水平，而不降低黄嘌呤氧化还原酶依赖的方式BAL蛋白。呼吸道组织学评价6小时后暴露于氯大鼠显着的支气管上皮脱落和炎性损伤。ip和im亚硝酸盐改善气道组织学相比，单独的Cl 2气体，但更多的覆盖面的立方或柱状上皮细胞的气道与ip亚硝酸盐相比，观察im。气道呈现更敏感的乙酰甲胆碱诱导的阻力和弹性后，氯气体暴露。有趣的是，im亚硝酸盐，而不是ip亚硝酸盐，显着降低气道敏感性乙酰甲胆碱挑战。进一步评估和比较im和ip治疗显示，前者循环亚硝酸盐水平增加了两倍，这与Cl 2清除后循环白细胞依赖性增加的逆转有关。IM亚硝酸盐剂量减半导致PMN积累没有影响，但BAL蛋白水平显着降低，表明一个明显的亚硝酸盐剂量依赖性抑制Cl 2依赖性肺通透性和炎症。这些数据突出了亚硝酸盐作为Cl 2气体诱导的肺损伤的暴露后治疗的潜力，并且还表明给药方式是亚硝酸盐治疗的关键考虑因素。
Cl2gas toxicity is complex and occurs during and after exposure, leading to acute lung injury (ALI) and reactive airway syndrome (RAS). Moreover, Cl2exposure can occur in diverse situations encompassing mass casualty scenarios, highlighting the need for postexposure therapies that are efficacious and amenable to rapid and easy administration. In this study, we assessed the efficacy of a single dose of nitrite (1mg/kg) to decrease ALI when administered to rats via intraperitoneal (ip) or intramuscular (im) injection 30min after Cl2exposure. Exposure of rats to Cl2gas (400ppm, 30min) significantly increased ALI and caused RAS 6–24h postexposure as indexed by BAL sampling of lung surface protein and polymorphonucleocytes (PMNs) and increased airway resistance and elastance before and after methacholine challenge. Intraperitoneal nitrite decreased Cl2-dependent increases in BAL protein but not PMNs. In contrast im nitrite decreased BAL PMN levels without decreasing BAL protein in a xanthine oxidoreductase-dependent manner. Histological evaluation of airways 6h postexposure showed significant bronchial epithelium exfoliation and inflammatory injury in Cl2-exposed rats. Both ip and im nitrite improved airway histology compared to Cl2gas alone, but more coverage of the airway by cuboidal or columnar epithelium was observed with im compared to ip nitrite. Airways were rendered more sensitive to methacholine-induced resistance and elastance after Cl2gas exposure. Interestingly, im nitrite, but not ip nitrite, significantly decreased airway sensitivity to methacholine challenge. Further evaluation and comparison of im and ip therapy showed a twofold increase in circulating nitrite levels with the former, which was associated with reversal of post-Cl2exposure-dependent increases in circulating leukocytes. Halving the im nitrite dose resulted in no effect in PMN accumulation but significant reduction of BAL protein levels, indicating a distinct nitrite dose dependence for inhibition of Cl2-dependent lung permeability and inflammation. These data highlight the potential for nitrite as a postexposure therapeutic for Cl2gas-induced lung injury and also suggest that administration modality is a key consideration in nitrite therapeutics.
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DOI：
10.1016/j.niox.2009.11.001
发表时间：
2010-02-15
期刊：
Nitric oxide : biology and chemistry
影响因子：
--
作者：
Calvert JW;Lefer DJ
通讯作者：
Lefer DJ
通过亚硝酸钠暴露后给药减轻大鼠氯气肺损伤。
DOI：
10.1152/ajplung.00278.2010
发表时间：
2011
期刊：
American journal of physiology. Lung cellular and molecular physiology
影响因子：
--
作者：
Yadav,AmitK;Doran,StephenF;Samal,AndreyA;Sharma,Ruchita;Vedagiri,Kokilavani;Postlethwait,EdwardM;Squadrito,GiuseppeL;Fanucchi,MichelleV;Roberts2nd,LJackson;Patel,RakeshP;Matalon,Sadis
通讯作者：
Matalon,Sadis
DOI：
10.1513/pats.201001-004sm
发表时间：
2010-07-01
期刊：
Proceedings of the American Thoracic Society
影响因子：
--
作者：
Bessac, Bret F;Jordt, Sven-Eric
通讯作者：
Jordt, Sven-Eric
DOI：
10.1513/pats.201001-006sm
发表时间：
2010
期刊：
Proceedings of the American Thoracic Society
影响因子：
--
作者：
Samal,Andrey;Honovar,Jaideep;White,CRoger;Patel,RakeshP
通讯作者：
Patel,RakeshP
DOI：
10.1513/pats.201001-008sm
发表时间：
2010-07-01
期刊：
Proceedings of the American Thoracic Society
影响因子：
--
作者：
White, Carl W;Martin, James G
通讯作者：
Martin, James G