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Penehyclidine hydrochloride attenuates LPS-induced acute lung injury involvement of NF-kappaB pathway.

Abstract
To investigate the protective effects of penehyclidine hydrochloride (PHC) in lipopolysaccharide (LPS)-induced acute lung injury (ALI) and the underlying molecular mechanism. ALI was induced by intravenous injection of LPS (5mg/kg). Male Sprague-Dawley (SD) rats challenged with or without LPS were pretreated with varied doses of PHC 0.5h before injection of LPS or saline. Blood gas in arterial blood, lung weight gain, bronchoalveolar lavage fluid (BALF), and neutrophils sequestration were examined 6h after administration of LPS. Pathological changes of lung tissue were measured by light microscopy. Phosphorylation of mitogen-activated protein kinase (MAPK) family and NF-kappaB were detected by western blot. All animals demonstrated drops in arterial oxygen tension (PaO(2)) after LPS application, which were significantly reversed by PHC pretreatment. Administration of PHC reduced lung water gain, bronchoalveolar lavage protein content, infiltration of neutrophils, malondialdehyde (MDA) content, and lactate dehydrogenase (LDH) activity and enhanced superoxide dismutase (SOD) activity. Histopathological study also indicated that PHC treatment markedly attenuated lung histopathological changes, alveolar hemorrhage, and inflammatory cells infiltration with evidence of decreasing of myeloperoxidase (MPO) activity. Furthermore, p38MAPK, ERK, and NF-kappaB were activated in 6h after LPS treatment, which could be blunted by PHC, while JNK remained unchanged. These findings confirmed significant protection by PHC against LPS-induced lung vascular leak and inflammation and implicated inhibition of p38MAPK activation signaling a potential role for PHC in the management of ALI.
AuthorsWeifeng Shen, Jianxin Gan, Shaowen Xu, Guanyu Jiang, Honghai Wu
JournalPharmacological research (Pharmacol Res) Vol. 60 Issue 4 Pg. 296-302 (Oct 2009) ISSN: 1096-1186 [Electronic] England
PMID19386282 (Publication Type: Journal Article)
Chemical References
  • Cholinergic Antagonists
  • Lipopolysaccharides
  • NF-kappa B
  • Quinuclidines
  • penehyclidine
  • Malondialdehyde
  • L-Lactate Dehydrogenase
  • Peroxidase
  • Superoxide Dismutase
  • Extracellular Signal-Regulated MAP Kinases
  • p38 Mitogen-Activated Protein Kinases
Topics
  • Acute Lung Injury (chemically induced, drug therapy)
  • Animals
  • Blood Gas Analysis
  • Bronchoalveolar Lavage Fluid (cytology, immunology)
  • Cholinergic Antagonists (pharmacology, therapeutic use)
  • Extracellular Signal-Regulated MAP Kinases (immunology)
  • L-Lactate Dehydrogenase (immunology)
  • Lipopolysaccharides
  • Lung (drug effects, immunology, pathology)
  • MAP Kinase Signaling System (drug effects)
  • Male
  • Malondialdehyde (immunology)
  • NF-kappa B (immunology)
  • Peroxidase (immunology)
  • Quinuclidines (pharmacology, therapeutic use)
  • Rats
  • Rats, Sprague-Dawley
  • Superoxide Dismutase (immunology)
  • p38 Mitogen-Activated Protein Kinases (immunology)

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