title: Protective effect of thioredoxin perfusion but not inhalation in warm ischemic-reperfused rat lungs.
abstract: BACKGROUND
  Thioredoxin is a ubiquitous protein with anti-oxidative, anti-apoptotic, and anti-inflammatory effects. It was reported [Fukuse T, Hirata T, Yokomise H et al. Attenuation of ischaemia reperfusion injury by human thioredoxin. Thorax 1995; 50: 387-391] that rhTRX protected lungs from ischemia-reperfusion injury as a radical scavenger; however, the mechanism was not elucidated. Therefore, we investigated the effect of perfusion and inhalation of rhTRX, and the associated mechanisms, by analyzing the concentrations and molecular states of the perfused rhTRX.
  
  
  METHODS
  Perfusion and inhalation studies of rhTRX were conducted with an isolated rat-lung perfusion model. The heart-lung block was perfused for 15 min and subsequently exposed to a 55-min ischemia followed by a 120-min reperfusion. Pulmonary artery pressure, weight gain, dynamic airway resistance, pulmonary compliance, and tidal volume were measured continuously. The concentrations and molecular states of the perfused rhTRX were measured.
  
  
  RESULTS
  A 350-microg/ml perfusion of rhTRX decreased post-ischemic pulmonary artery pressure (P < 0.05), while a 200-microg/ml perfusion did not. Throughout the experiment, the rhTRX concentrations were constant, and the rhTRX molecules were mostly dimeric. The inhalation of rhTRX showed adverse effects on the pulmonary function compared with the control group (P < 0.05).
  
  
  CONCLUSIONS
  A 350-microg/ml perfusion, but not inhalation, of rhTRX protected rat lungs from ischemia-reperfusion injury. rhTRX was effective in dimeric form without transit to the lung tissue. rhTRX may be effective by some mechanism other than radical scavenging.
authors.affiliation: Department of Thoracic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Jitian
authors.initials: J
authors.lastname: Zhang
authors.forename: Fengshi
authors.initials: F
authors.lastname: Chen
authors.forename: Takayuki
authors.initials: T
authors.lastname: Nakamura
authors.forename: Takuji
authors.initials: T
authors.lastname: Fujinaga
authors.forename: Akihiro
authors.initials: A
authors.lastname: Aoyama
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hamakawa
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Sakai
authors.forename: Yuma
authors.initials: Y
authors.lastname: Hoshino
authors.forename: Junji
authors.initials: J
authors.lastname: Yodoi
authors.forename: Hiromi
authors.initials: H
authors.lastname: Wada
authors.forename: Toru
authors.initials: T
authors.lastname: Bando
authors.forename: Hajime
authors.initials: H
authors.lastname: Nakamura
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000502:physiology; D008297:Male; D010477:Perfusion; D011897:Random Allocation; D051381:Rats; D011917:Rats, Inbred Lew; D015427:Reperfusion Injury / Q000188:drug therapy / Q000517:prevention & control*; D012709:Serum Albumin / Q000378:metabolism; D013879:Thioredoxins / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D012709:Serum Albumin; C491203:TXN protein, human; C001702:mercaptoalbumin; D013879:Thioredoxins