title: Effects of peripheral benzodiazepine receptor ligand Ro5-4864 in four animal models of acute lung injury.
abstract: BACKGROUND
  Acute lung injury (ALI) is a syndrome of inflammation and increased permeability of the blood-gas barrier. It is associated with high morbidity and mortality. Despite intensive research, treatments remain limited. The aim of the present study was to investigate the protective efficacy of a specific peripheral benzodiazepine receptor ligand, Ro5-4864, in experimental models of ALI in rats.
  
  
  METHODS
  ALI was generated by four different methods: (1) intravenous (tail vein) injection of Escherichia coli (0111:B4) lipopolysaccaride (LPS), (2) cecal ligation and puncture (CLP), (3) mesenteric ischemia/reperfusion, and (4) intraperitoneal injection of α-naphthylthiourea (ANTU). Ro5-4864 was administered to rats intraperitoneally 30 min before ANTU and LPS administration or intravenously 15 min before reperfusion and CLP. The levels of pulmonary edema (lung weight/body weight ratio) and pleural effusion were measured, and the severity of ALI was scored (0-3).
  
  
  RESULTS
  Ro5-4864 showed a dose-dependent and significant prophylactic effect on the ANTU-induced lung weight/body weight and pleural effusion/body weight ratios and histopathologic scores. Ro5-4864 also showed significant prophylactic effects against the LPS-induced lung weight/body weight ratio and histopathologic scores. Ro5-4864 significantly decreased the intra-alveolar edema and perialveolar hemorrhage scores in the CLP group. However, we found no prophylactic effect of Ro5-4864 on mesenteric ischemia/reperfusion-induced ALI at the dose used (2 mg/kg intraperitoneally).
  
  
  CONCLUSIONS
  These results have demonstrated, for the first time, a protective effect of Ro5-4864 on experimental ALI induced by ANTU, LPS, and CLP. Ro5-4864 might be a useful therapeutic agent for lung diseases, including ALI, in intensive care patients.
authors.affiliation: Department of Pharmacology, Health Science Institute, Bulent Ecevit University, Kozlu, Zonguldak, Turkey.
authors.forename: Gulcan
authors.initials: G
authors.lastname: Kaynar
authors.forename: Gamze
authors.initials: G
authors.lastname: Yurdakan
authors.forename: Fusun
authors.initials: F
authors.lastname: Comert
authors.forename: Emine
authors.initials: E
authors.lastname: Yilmaz-Sipahi
mesh_terms: D055371:Acute Lung Injury / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D000818:Animals; D001570:Benzodiazepinones / Q000627:therapeutic use*; D004195:Disease Models, Animal; D058785:GABA-A Receptor Agonists / Q000627:therapeutic use*; D008070:Lipopolysaccharides / Q000633:toxicity; D008168:Lung / Q000473:pathology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000502:physiology; D015996:Survival Rate; D013890:Thiourea / Q000031:analogs & derivatives / Q000633:toxicity
chemical_list: D001570:Benzodiazepinones; D058785:GABA-A Receptor Agonists; D008070:Lipopolysaccharides; D011963:Receptors, GABA-A; C028513:4'-chlorodiazepam; D013890:Thiourea; C005277:alpha-naphthyl thiourea