Thioredoxin-1 Attenuates Early Graft Loss after Intraportal Islet Transplantation in Mice

Abstract

Aims: Recent studies suggest that decreasing oxidative stress is crucial to achieve successful islet transplantation. Thioredoxin-1 (TRX), which is a multifunctional redox-active protein, has been reported to suppress oxidative stress. Furthermore, it also has anti-inflammatory and anti-apoptotic effects. In this study, we investigated the effects of TRX on early graft loss after islet transplantation.Methods: Intraportal islet transplantation was performed for two groups of streptozotocin-induced diabetic mice: a control and a TRX group. In addition, TRX-transgenic (Tg) mice were alternately used as islet donors or recipients.Results: The changes in blood glucose levels were significantly lower in the TRX group compared with the TRX-Tg donor and control groups (p,0.01). Glucose tolerance and the residual graft mass were considerably better in the TRX group. TRX significantly suppressed the serum levels of interleukin-1b (p,0.05), although neither anti-apoptotic nor anti-chemotactic effects were observed. Notably, no increase in the 8-hydroxy-29-deoxyguanosine level was observed after islet infusion, irrespective of TRX administration. Conclusions:The present study demonstrates that overexpression of TRX on the islet grafts is not sufficient to improve engraftment. In contrast, TRX administration to the recipients exerts protective effects on transplanted islet grafts by suppressing the serum levels of interleukin-1b. However, TRX alone appears to be insufficient to completely prevent early graft loss after islet transplantation. We therefore propose that a combination of TRX and other anti-inflammatory treatments represents a promising regimen for improving the efficacy of islet transplantation.

Thioredoxin Protects Skin Flaps from Ischemia-Reperfusion Injury

“…5 Thioredoxin-1 is the most common member of the family in mammals, executing its duplicate function as an endogenous reactive oxygen species scavenger and antiapoptotic messenger in a variety of ischemia-reperfusion tissues and organs. [6][7][8][9][10] Furthermore, administering the recombinant human thioredoxin-1 has been confirmed in animal models to attenuate disorders caused by oxidative stress, including cerebral ischemia, 11 autoimmune myocarditis, 12 and ultraviolet-B-mediated skin injury. 13 However, little is known about the effects of thioredoxin-1 on free flap ischemia-reperfusion injury.…”

KRP-203 Is a Desirable Immunomodulator for Islet Allotransplantation

“…Islet isolation was performed as previously described. 11 On day 15, KRP-203-treated (3 mg/kg) and control mice were anesthetized by isoflurane inhalation (Abbott Japan Co., Ltd., Tokyo, Japan). The bile duct was identified and clamped at the papilla of Vateri.…”

“…We evaluated the islet respiratory activity using scanning electrochemical microscopy as described previously. 11,13 In brief, the respiratory activity of 5 hand-picked islets in each group was calculated by evaluating the difference in the reduction current around the samples using 2-4 μm platinum-coated microelectrodes. The glucose-stimulated respiratory activity was indicated by the stimulation index of the respiratory activity, defined as the ratio of the respiratory activity at a high glucose concentration (16.7 mmol/L) against that at the basal glucose concentration (1.67 mmol/L) (n = 4 per group).…”