Pentoxifylline inhibits intercellular adhesion molecule-1 (ICAM-1) and lung injury in experimental phosgene-exposure rats.
Phosgene inhalation results in acute lung injury (ALI) mostly, pulmonary edema and even acute respiratory distress syndrome, but there is no specific antidote. Inflammatory cells play an important role in the ALI caused by phosgene. Intercellular adhesion molecule-1 (ICAM-1) is a critical factor for inflammatory organ injury. We hypothesized that pentoxifylline (PTX), an inhibitor of leukocyte activation, would have a protective effect on experimental phosgene-induced lung injury rats by inhibiting ICAM-1. To prove this hypothesis, we used rat models of phosgene (400 ppm x 1 min)-induced injury to investigate: (1) the time course of lung injury (control 1, 3, 6, 12, 24, and 48 h group), including pathological changes in hematoxylin and eosin staining and transmission electron microscope, myeloperoxidase (MPO) activity by colorimetric method and ICAM-1 protein level detected by western blot, (2) At 3 h after phosgene exposure, protective effects of different dosages of PTX (50 mg/kg and 100 mg/kg) administration were evaluated by MPO activity, ICAM-1 differential expression and WBC count in bronchoalveolar lavage fluid. The results showed that inflammatory cells emerged out of lung blood vessels at 3 h after phosgene exposure. The MPO activity of lung tissue increased significantly from 3 to 48 h after phosgene exposure (P < 0.05) and ICAM-1 expression presented a similar change, especially at 3 h and 24 h (P < 0.05). After pretreatment and treatment with PTX (100 mg/kg), significant protective effects were shown (P < 0.05). These data supported our hypothesis that PTX reduced phosgene-induced lung injury, possibly by inhibiting ICAM-1 differential expression.
Zhang
Xiao-di
XD
Department of Toxicology, the Fourth Military Medical University, Xi'an, PR China.
Hou
Jun-Feng
JF
Qin
Xu-Jun
XJ
Li
Wen-Li
WL
Chen
Hong-Li
HL
Liu
Rui
R
Liang
Xin
X
Hai
Chun-Xu
CX
D000818:Animals; D019570:Inhalation Exposure / Q000009:adverse effects; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis*; D055370:Lung Injury / Q000139:chemically induced / Q000378:metabolism* / Q000517:prevention & control*; D008297:Male; D010431:Pentoxifylline / Q000494:pharmacology* / Q000627:therapeutic use*; D009195:Peroxidase / Q000037:antagonists & inhibitors / Q000378:metabolism; D010705:Phosgene / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley
D010705:Phosgene; D018799:Intercellular Adhesion Molecule-1; D009195:Peroxidase; D010431:Pentoxifylline