Protective effect of thioredoxin perfusion but not inhalation in warm ischemic-reperfused rat lungs.
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.
Zhang
Jitian
J
Department of Thoracic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Chen
Fengshi
F
Nakamura
Takayuki
T
Fujinaga
Takuji
T
Aoyama
Akihiro
A
Hamakawa
Hiroshi
H
Sakai
Hiroaki
H
Hoshino
Yuma
Y
Yodoi
Junji
J
Wada
Hiromi
H
Bando
Toru
T
Nakamura
Hajime
H
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
D012709:Serum Albumin; C491203:TXN protein, human; C001702:mercaptoalbumin; D013879:Thioredoxins