PROTECTION AGAINST REPERFUSION-INDUCED ARRHYTHMIAS BY HUMAN THIOREDOXIN

Adult T-cell leukemia-derived factor (ADF), identified in the supernat ant of adult T-cell leukemia (ATL) cell culture, is a human homologue of thioredoxin and consists of 104 amino acids; it has two redox-activ e half-cysteine residues in an exposed active center. Human thioredoxi n has many biological activities, including growth promotion, cell act ivation, and a catalase-like radical scavenging activity. We examined the protective effect of human thioredoxin (h-thioredoxin) against rep erfusion-induced arrhythmias in an isolated rat heart model with 10-mi n regional ischemia followed by 30-min reperfusion. Male Wistar rats w ere 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 [similar to 0.01 mu M (TRX-I group), simila r to 0.1 mu M (TRX-II group), and similar to 1 mu M (TRX-III group)]. In the early reperfusion period, h-thioredoxin reduced the incidence o f ventricular fibrillation (VF) to 8% in the TRX-II group (p < 0.01) f rom the control value of 75%. SOD and catalase reduced the incidence o f VF to 43 and 33%, respectively (NS). During the entire reperfusion p eriod, 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 inciden ce of VF was significantly reduced to 42 and 25%, respectively. These findings indicate that SOD failed to protect against the reperfusion-i nduced arrhythmias. h-Thioredoxin exerted a protective effect against these arrhythmias; a concentration of similar to 0.1 mu M was the most effective.