Effects of early administration of a novel anticholinergic drug on acute respiratory distress syndrome induced by sepsis

Med Sci Monit. 2011 Nov;17(11):BR319-325. doi: 10.12659/msm.882041.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bronchoalveolar Lavage Fluid / chemistry
  • Cholinergic Antagonists / administration & dosage
  • Cholinergic Antagonists / pharmacology*
  • Cholinergic Antagonists / therapeutic use
  • Injections, Intraperitoneal
  • Interleukin-6 / blood
  • Malondialdehyde / blood
  • Nitrates / blood
  • Nitrites / blood
  • Quinuclidines / administration & dosage
  • Quinuclidines / pharmacology*
  • Quinuclidines / therapeutic use
  • Rats
  • Rats, Sprague-Dawley
  • Respiratory Distress Syndrome / drug therapy*
  • Respiratory Distress Syndrome / etiology*
  • Sepsis / complications*
  • Statistics, Nonparametric
  • Superoxide Dismutase / blood
  • Survival Analysis
  • Tumor Necrosis Factor-alpha / blood

Substances

  • Cholinergic Antagonists
  • Interleukin-6
  • Nitrates
  • Nitrites
  • Quinuclidines
  • Tumor Necrosis Factor-alpha
  • penehyclidine
  • Malondialdehyde
  • Superoxide Dismutase