Attenuation of ischaemia reperfusion injury by human thioredoxin.

Abstract

Background -Active oxygen species are thought to play a part in ischaemia reperfusion injury. The ability of a novel agent, human thioredoxin (hTRX), to attenuate lung damage has been examined in a rat model of ischaemia reperfusion injury.Methods -Twenty eight animals were studied. At thoracotomy the left main bronchus and the left main pulmonary artery were clamped for 75 minutes and the lung was then reperfused for 20 minutes. Phosphate buffered saline was administered intravenously to nine control animals and hTRX (30 pg/g body weight)was given intravenously to another group of nine animals. Two experiments were carried out. The first (Exp 1) was a time matched pair experiment (five treated, five controls), and the second (Exp 2) was performed under controlied conditions (four treated, four controls; temperature 25°C, humidity 65%). In another 10 nonischaemic rats and those in Exp 1 biochemical measurements of lipid peroxide, superoxide dismutase, and glutathione peroxide levels were performed. Results -In both experiments rats perfused with hTRX survived longer than controls. In Exp 1 the arterial oxygen tension (Pao2) on air in the hTRX group was higher at 20 minutes than at one minute after reperfusion. In Exp 2 Pao2 at 20 minutes was higher in the hTRX group than in the controls. Lipid peroxide, superoxide dismutase, and glutathione peroxide levels in the control group were higher than in the hTRX group and in the non-ischaemic groups. Histological examination showed less thickening and oedema of the alveolar walls in the hTRX group than in controls. Conclusions -These results suggest that hTRX is effective as a radical scavenger and can limit the extent of ischaemia reperfusion injury of the lungs of experimental animals. (Thorax 1995;50:387-391)

Human thioredoxin attenuates hypoxia-reoxygenation injury of murine endothelial cells in a thiol-free condition

“…It consists of 104 amino acids with a molecular weight of 12 kDa, and acts as a hydrogen donor. Recently, we reported the protective effects of ADF/hTRX against ischemia reperfusion-induced lung injury in rats, rabbits, and dogs (Fukuse et al, 1995;Okubo et al, 1997;Wada et al, 1995;Yagi et al, 1994;Yokomise et al, 1994). We also demonstrated that ADF/hTRX suppressed reperfusion-induced arrhythmia in an isolated rat heart model (Aota et al, 1996).…”

“…Exogenous ADF/hTRX was reported to protect cells from oxidative stress in vitro (Mitsui et al, 1992;Nakamura et al, 1994), ex vivo (Aota et al, 1996;Wada et al, 1995), or in vivo (Fukuse et al, 1995;Okubo et al, 1997;Yagi et al, 1994;Yokomise et al, 1994). Two different mechanisms of the cytoprotective effects have been proposed (Nakamura et al, 1997).…”

Stat3 confers resistance against hypoxia/reoxygenation-induced oxidative injury in hepatocytes through upregulation of Mn-SOD

“…H/R-induced apoptosis is considered to result mainly from ROS generation [3], and a number of reports showed that reduced ROS generation suppressed injury after reoxygenation by catalytic anti-oxidants [38,39] or antioxidative enzymes including catalase [40], GPx [41], Cu/ Zn-SOD [42], Mn-SOD [10] and TRX [43]. In the present study, ROS generation after H/R was suppressed by Stat3 overexpression.…”

Stressing the obvious? Cell stress and cell stress proteins in cardiovascular disease

“…Levels of Trx are elevated in atherosclerotic plaques and in endothelial cells during neointimal regeneration following ballon injury [82]. Overexpression of Trx in transgenic mice ameliorates focal ischemic brain damage or adriamycininduced cardiotoxicity [83] and administration of soluble Trx inhibits ischemia reperfusion injury in various experimental models [84][85][86][87]. Do soluble forms of the other cardioprotective CSPs block ischemic injury?…”