title: Liver reperfusion-induced decrease in dynamic compliance and increase in airway resistance are ameliorated by preischemic treatment with melatonin through scavenging hydroxyl radicals in rat lungs.
abstract: OBJECTIVE
  Acute lung injury is frequently observed in patients subsequent to liver ischemia and reperfusion (I/R) injury. However, the changes in pulmonary function, eg, lung dynamic compliance (C(dyn)) and airway resistance (RI), are not well understood. We sought to study the alternations in pulmonary function during liver I/R and the protective effects of preischemic treatment with melatonin.
  
  
  METHODS
  Animals were divided into 3 groups: sham-operated, liver I/R, and intraperitoneal (i.p.) pretreatment with melatonin (15 mg/kg). Liver I/R was performed by clamping the hepatic artery and portal vein for 30 minutes followed by releasing for 2 hours. The C(dyn) and RI were studied at baseline and at 2 hours of reperfusion. We assessed the level of pulmonary hydroxyl radicals by methylguanidine (MG) content in the bronchoalveolar lavage fluid (BALF) as well as the liver damage using plasma levels of lactate dehydrogenase (LDH), glutamic oxaloacetic transaminase (GOT), and glutamic pyruvic transaminase (GPT).
  
  
  RESULTS
  After 2 hours of liver reperfusion, C(dyn) was reduced by ∼25%, while RI increased by ∼16% (P < .05). The decreased C(dyn) and increased RI were markedly attenuated by melatonin pretreatment (P < .05). Melatonin pretreatment also protected the liver against I/R injury (P < .05), as seen by reduced LDH, GOT and GPT along with markedly reduced hydroxyl radicals (P < .05).
  
  
  CONCLUSIONS
  Preischemic treatment with melatonin protected lung function against damage by liver I/R. The improvement in lung function was strongly associated with decreased hydroxyl radicals in the lungs.
authors.affiliation: Department of Neurology, Shin Kong Wu Ho Su Memorial Hospital, Taipei, Taiwan.
authors.forename: J-H
authors.initials: JH
authors.lastname: Yeh
authors.forename: C-L
authors.initials: CL
authors.lastname: Su
authors.forename: C F
authors.initials: CF
authors.lastname: Chen
authors.forename: D
authors.initials: D
authors.lastname: Wang
authors.forename: J-J
authors.initials: JJ
authors.lastname: Wang
mesh_terms: D055371:Acute Lung Injury / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D000403:Airway Resistance / Q000187:drug effects*; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D015415:Biomarkers / Q000097:blood; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D019610:Cytoprotection; D004195:Disease Models, Animal; D016166:Free Radical Scavengers / Q000494:pharmacology*; D017665:Hydroxyl Radical / Q000378:metabolism*; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008107:Liver Diseases / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D008170:Lung Compliance / Q000187:drug effects; D008297:Male; D008550:Melatonin / Q000494:pharmacology; D008760:Methylguanidine / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
chemical_list: D015415:Biomarkers; D016166:Free Radical Scavengers; D017665:Hydroxyl Radical; D008760:Methylguanidine; D007770:L-Lactate Dehydrogenase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D008550:Melatonin