Renoprotective effect of long acting thioredoxin by modulating oxidative stress and macrophage migration inhibitory factor against rhabdomyolysis-Associated acute kidney injury
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Rhabdomyolysis-Associated acute kidney injury (AKI) is a serious life-Threatening condition. As such, more effective strategies are needed for its prevention. Thioredoxin-1 (Trx), a redox-Active and macrophage migration inhibitory factor (MIF) modulating protein, has a short retention time in the blood. We examined the renoprotective effect of long acting Trx that was genetically fused with human serum albumin (HSA-Trx) against glycerol-induced AKI. An intravenous HSA-Trx pre-Treatment attenuated the glycerol-induced decline in renal function, compared to a PBS, HSA or Trx alone. HSA-Trx caused a reduction in the tubular injuries and in the number of apoptosis-positive tubular cells. Renal superoxide, 8-hydroxy deoxyguanosine, nitrotyrosine and the plasma Cys34-cysteinylated albumin were clearly suppressed by the HSA-Trx treatment. Prior to decreasing TNF-a and IL-6, HSA-Trx suppressed an increase of plasma MIF level. In LLC-PK1 cells, HSA-Trx decreased the level of reactive oxygen species and lactate dehydrogenase release induced by myoglobin. HSA-Trx treatment resulted in a threefold increase in the survival of lethal glycerol-Treated mice. The post-Administration of HSA-Trx at 1 and 3â €‰hr after glycerol injection exerted a significant renoprotective effect. These results suggest HSA-Trx has potential for use in the treatment of rhabdomyolysis-Associated AKI via its extended effects of modulating oxidative stress and MIF.
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