Protection against reperfusion-induced arrhythmias by human thioredoxin.
Adult T-cell leukemia-derived factor (ADF), identified in the supernatant of adult T-cell leukemia (ATL) cell culture, is a human homologue of thioredoxin and consists of 104 amino acids; it has two redox-active half-cysteine residues in an exposed active center. Human thioredoxin has many biological activities, including growth promotion, cell activation, and a catalase-like radical scavenging activity. We examined the protective effect of human thioredoxin (h-thioredoxin) against reperfusion-induced arrhythmias in an isolated rat heart model with 10-min regional ischemia followed by 30-min reperfusion. Male Wistar rats were assigned to six groups: a control, a superoxide dismutase (SOD 8 x 10(4) IU/L), and a catalase group (1 x 10(6) IU/L), and three groups treated with h-thioredoxin [approximately .01 microM (TRX-I group), approximately 0.1 microM (TRX-II group), and approximately 1 microM (TRX-III group)]. In the early reperfusion period, h-thioredoxin reduced the incidence of ventricular fibrillation (VF) to 8% in the TRX-II group (p < 0.01) from the control value of 75%. SOD and catalase reduced the incidence of VF to 43 and 33%, respectively (NS). During the entire reperfusion period, the incidence of VF in the SOD group was 79%, as compared to 83% in the control group. In the catalase and TRX-II groups, the incidence of VF was significantly reduced to 42 and 25%, respectively. These findings indicate that SOD failed to protect against the reperfusion-induced arrhythmias. h-Thioredoxin exerted a protective effect against these arrhythmias; a concentration of approximately 0.1 micro was the most effective.
Aota
M
M
Department of Cardiovascular Surgery, Faculty of Medicine, Kyoto University, Kyoto, Japan.
Matsuda
K
K
Isowa
N
N
Wada
H
H
Yodoi
J
J
Ban
T
T
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000517:prevention & control*; D002374:Catalase / Q000494:pharmacology; D006801:Humans; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000494:pharmacology; D013879:Thioredoxins / Q000494:pharmacology*
D011994:Recombinant Proteins; D013879:Thioredoxins; D002374:Catalase; D013482:Superoxide Dismutase