Effects of early administration of a novel anticholinergic drug on acute respiratory distress syndrome induced by sepsis
Hao Li, Zhaoxin Qian, Jianmin Li, Xiaotong Han, Min Liu
Med Sci Monit 2011; 17(11): BR319-325
Background: Acute respiratory distress syndrome (ARDS) is the inflammatory disorder of the lung most commonly caused by sepsis. It was hypothesized that treating the lung with penehyclidine hydrochloride (PHC), a new type of hyoscyamus drug, early in the development of sepsis could diminish the lung dysfunction.
Material/Methods: Sprague-Dawley rats were divided into 4 groups: 1) a control group; 2) a sham-operated group; 3) a cecal ligation and puncture (CLP) group; 4) a PHC-treated group. One hour after CLP surgery, rats were either untreated or treated with PHC via intraperitoneal injection. Lung wet/dry weight ratio, bronchoalveolar lavage fluid (BALF), serum tumor necrosis factor (TNF-α), interleukin 6 (IL-6), interleukin 10 (IL-10), total nitrite/nitrate (NOx), superoxide dismutase (SOD), malondialdehyde (MDA) in lung tissues, and pulmonary functions were examined 24 hour after surgery. Another 60 rats were randomly assigned to 4 equal groups to observe survival status 96 hours after surgery.
Results: Treatment of PHC markedly decreased TNF-α, IL-6, NOx, SOD, MDA content, protein concentration in BALF, and lung wet/dry weight ratio and enhanced SOD activity (p<0.05), which are indicative of PHC-induced suppression in the pathogenesis of ARDS caused by sepsis. In comparison to group CLP/saline, plasma IL-10 level markedly increased in group CLP/PHC. In PHC-treated groups, the administered PHC had a significant protective effect on the lung dysfunction induced by sepsis.
Conclusions: We conclude that administration of PHC at the time of a systemic insult can protect the lung from the damaging effects of sepsis.
Keywords: Sepsis - complications, Respiratory Distress Syndrome, Adult - etiology, Rats, Sprague-Dawley, Rats, Quinuclidines - therapeutic use, Nitrites - blood, Nitrates - blood, Malondialdehyde - blood, Interleukin-6 - blood, Injections, Intraperitoneal, Cholinergic Antagonists - therapeutic use, Bronchoalveolar Lavage Fluid - chemistry, Animals, Statistics, Nonparametric, Superoxide Dismutase - blood, Survival Analysis, Tumor Necrosis Factor-alpha - blood