Methylene chloride protects against cecal ligation and puncture-induced acute lung injury by modulating inflammatory mediators.
Recent studies suggest that exogenously administered CO is beneficial for the resolution of acute pulmonary inflammation. In this study, we assessed the role of CO donor, methylene chloride (MC), on modulation of lung inflammation during sepsis. Acute lung injury in Sprague-Dawley rats was induced by cecal ligation and perforation (CLP). MC (100mg/kg) was intragastrically administered 2h before CLP induction. Lung tissues and lavage samples were isolated for biochemical determinations and histological measurements 10h after CLP operation. In addition, we investigated survival rate with the other 40 rats. Intragastric administration with MC significantly decreased morbidity and mortality of CLP-induced ALI as confirmed by blinded histological changes, myeloperoxidase activity, mortality, and the content of TNF-alpha and IL-10. This protective effect could be abolished by an MC inhibitor, disulfiram. These results suggested that MC has obvious protective effects against CLP-induced ALI in rats. The mechanism of the protective effects partly involves modulating inflammatory mediators.
Pang
Qingfeng
Q
Department of Pathophysiology, Xuzhou Medical College, Xuzhou, Jiangsu 221002, China. qfpang@yahoo.com.cn
Dou
Lidong
L
Pan
Xiuhua
X
Zeng
Si
S
He
Jun
J
Xu
Wenli
W
Zeng
Yinming
Y
D055371:Acute Lung Injury / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D002248:Carbon Monoxide / Q000737:chemistry / Q000494:pharmacology; D002432:Cecum / Q000473:pathology / Q000601:surgery*; D019610:Cytoprotection / Q000187:drug effects; D004195:Disease Models, Animal; D004221:Disulfiram / Q000494:pharmacology; D006801:Humans; D056747:Immunomodulation; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism; D008752:Methylene Chloride / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D009195:Peroxidase / Q000037:antagonists & inhibitors; D011014:Pneumonia; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics
D018836:Inflammation Mediators; D014409:Tumor Necrosis Factor-alpha; D008752:Methylene Chloride; D002248:Carbon Monoxide; D009195:Peroxidase; D004221:Disulfiram