title: MK-571 attenuates kidney ischemia and reperfusion-induced airway hypersensitivity in rats.
abstract: OBJECTIVE
  Reperfusion of the rat kidney has been shown to up-regulate cysteinyl leukotriene-1 receptor, an asthma-associated gene in human bronchioles, and increase expression of leukotriene D4. In this study, we aimed to investigate the efficacy of MK-571, a leukotriene D4 inhibitor, against hypersensitivity induced by kidney ischemia and reperfusion (I/R)-associated acute kidney injury.
  
  
  METHODS
  Sprague-Dawley male rats were divided into 3 study groups: a sham-operated group, a kidney I/R group, and a group treated with MK-571 before the kidney I/R injury: MK-571 (5 mg/kg) was administered intraperitoneally 15 minutes before ischemia and every 12 hours after reperfusion up to 24 hours. Ischemia was conducted by bilateral occlusion of renal pedicles for 45 minutes, followed by releasing the clamps and closing the abdominal incision. Respiratory function was tested 24 hours after reperfusion, with the use of a 2-chamber whole body plethysmograph for conscious rats. Blood samples, pulmonary bronchoalveolar lavage fluid, and lung tissues were collected at the end of study. In 10 rats, urine was collected at baseline and the end of study.
  
  
  RESULTS
  Compared with the sham group, kidney I/R injury markedly increased enhanced pause (Penh) index during methacholine challenge test (P < .05), suggesting airway hypersensitivity; it also increased in inflammatory response and levels of hydroxyl radical production and lipid peroxidation in the lungs. In contrast, in MK-571-treated rats, Penh was muted during methacholine challenge test (P < .05).
  
  
  CONCLUSIONS
  Kidney I/R injury induces airway hypersensitivity to methacholine challenge test and inflammatory response and oxidative stress in the lungs. Treatment with MK-571, a leukotriene D4 inhibitor, effectively attenuates airway hypersensitivity, pulmonary inflammatory response, and lung and kidney injury.
authors.affiliation: Division of Cardiovascular Surgery, Department of Surgery, Chi-Mei Foundation Hospital, Tainan, Taiwan.
authors.forename: N-C
authors.initials: NC
authors.lastname: Wu
authors.affiliation: Department of Medicine, School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan.
authors.forename: S-P
authors.initials: SP
authors.lastname: Tong
authors.affiliation: Department of Medicine, School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan.
authors.forename: Y-C
authors.initials: YC
authors.lastname: Yang
authors.affiliation: Department of Medicine, School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan.
authors.forename: J-C
authors.initials: JC
authors.lastname: Wang
authors.affiliation: Department of Medicine, School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan. Electronic address: 078625@mail.fju.edu.tw.
authors.forename: J-J
authors.initials: JJ
authors.lastname: Wang
mesh_terms: D058186:Acute Kidney Injury / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D015415:Biomarkers / Q000378:metabolism; D016535:Bronchial Hyperreactivity / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D016084:Bronchoconstriction / Q000187:drug effects*; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D017665:Hydroxyl Radical / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D007274:Injections, Intraperitoneal; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D020024:Leukotriene Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D011422:Propionates / Q000008:administration & dosage / Q000494:pharmacology*; D011804:Quinolines / Q000008:administration & dosage / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D013997:Time Factors
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D015415:Biomarkers; D001993:Bronchodilator Agents; D018836:Inflammation Mediators; D020024:Leukotriene Antagonists; D011422:Propionates; D011804:Quinolines; D017665:Hydroxyl Radical; C059141:verlukast