The Prophylactic and Therapeutic Effects of Cholinolytics on Perfluoroisobutylene Inhalation Induced Acute Lung Injury

Abstract

Perfluoroisobutylene (PFIB) is a kind of fluoro-olefin that is ten times more toxic than phosgene. The mechanisms of the acute lung injury (ALI) induced by PFIB inhalation remain unclear. To find possible pharmacological interventions, mice and rats were exposed to PFIB, and the prophylactic or therapeutic effects of 3-quinuclidinyl benzilate (QNB) and anisodamine were studied and confirmed. It was observed that the wet lung/body weight and the dry lung/body weight ratios at 24 h after PFIB exposure (130 mg/m(3) for 5 min) were significantly decreased when a single dose of QNB (5 mg/kg) was administered intraperitoneally either 30 min before exposure or 10 h after exposure. Anisodamine was without any prophylactic or therapeutic effects at single doses below 30 mg/kg. The effects of QNB against PFIB inhalation induced ALI were well evidenced by the significantly decreased mice mortality at 72 h, the total protein concentration in bronchoalveolar lavage fluid at 24 h after the PFIB exposure, as well as the ultrastructural observations. The analysis of the time courses of lung sulfhydryl concentration, myeloperoxidase (MPO) activity and hemorheology assay showed that the toxicity of PFIB may be due to consumption of lung protein sulfhydryl, influx of polymorphonuclear leukocytes (PMNs) into the lung, and increased peripheral blood viscosity at a low shear rate, all of which were partially blocked by QNB intervention except for PMN influx. The results suggest that cholinolytics might have prophylactic and therapeutic roles in PFIB inhalation induced ALI.