Renoprotective effect of long acting thioredoxin by modulating oxidative stress and macrophage migration inhibitory factor against rhabdomyolysis-Associated acute kidney injury

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 bl...

Full description

Bibliographic Details
Main Authors: Nishida, K., Watanabe, H., Ogaki, S., Kodama, A., Tanaka, R., Imafuku, T., Ishima, Y., Toyoda, M., Kondoh, M., Wu, Q., Fukagawa, M., Otagiri, M., Maruyama, T., Chuang, Victor
Format: Journal Article
Published: 2015
Online Access:http://hdl.handle.net/20.500.11937/9945
_version_ 1848746095936536576
author Nishida, K.
Watanabe, H.
Ogaki, S.
Kodama, A.
Tanaka, R.
Imafuku, T.
Ishima, Y.
Toyoda, M.
Kondoh, M.
Wu, Q.
Fukagawa, M.
Otagiri, M.
Maruyama, T.
Chuang, Victor
author_facet Nishida, K.
Watanabe, H.
Ogaki, S.
Kodama, A.
Tanaka, R.
Imafuku, T.
Ishima, Y.
Toyoda, M.
Kondoh, M.
Wu, Q.
Fukagawa, M.
Otagiri, M.
Maruyama, T.
Chuang, Victor
author_sort Nishida, K.
building Curtin Institutional Repository
collection Online Access
description 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.
first_indexed 2025-11-14T06:27:49Z
format Journal Article
id curtin-20.500.11937-9945
institution Curtin University Malaysia
institution_category Local University
last_indexed 2025-11-14T06:27:49Z
publishDate 2015
recordtype eprints
repository_type Digital Repository
spelling curtin-20.500.11937-99452017-09-13T14:53:17Z Renoprotective effect of long acting thioredoxin by modulating oxidative stress and macrophage migration inhibitory factor against rhabdomyolysis-Associated acute kidney injury Nishida, K. Watanabe, H. Ogaki, S. Kodama, A. Tanaka, R. Imafuku, T. Ishima, Y. Toyoda, M. Kondoh, M. Wu, Q. Fukagawa, M. Otagiri, M. Maruyama, T. Chuang, Victor 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. 2015 Journal Article http://hdl.handle.net/20.500.11937/9945 10.1038/srep14471 unknown
spellingShingle Nishida, K.
Watanabe, H.
Ogaki, S.
Kodama, A.
Tanaka, R.
Imafuku, T.
Ishima, Y.
Toyoda, M.
Kondoh, M.
Wu, Q.
Fukagawa, M.
Otagiri, M.
Maruyama, T.
Chuang, Victor
Renoprotective effect of long acting thioredoxin by modulating oxidative stress and macrophage migration inhibitory factor against rhabdomyolysis-Associated acute kidney injury
title Renoprotective effect of long acting thioredoxin by modulating oxidative stress and macrophage migration inhibitory factor against rhabdomyolysis-Associated acute kidney injury
title_full Renoprotective effect of long acting thioredoxin by modulating oxidative stress and macrophage migration inhibitory factor against rhabdomyolysis-Associated acute kidney injury
title_fullStr Renoprotective effect of long acting thioredoxin by modulating oxidative stress and macrophage migration inhibitory factor against rhabdomyolysis-Associated acute kidney injury
title_full_unstemmed Renoprotective effect of long acting thioredoxin by modulating oxidative stress and macrophage migration inhibitory factor against rhabdomyolysis-Associated acute kidney injury
title_short Renoprotective effect of long acting thioredoxin by modulating oxidative stress and macrophage migration inhibitory factor against rhabdomyolysis-Associated acute kidney injury
title_sort renoprotective effect of long acting thioredoxin by modulating oxidative stress and macrophage migration inhibitory factor against rhabdomyolysis-associated acute kidney injury
url http://hdl.handle.net/20.500.11937/9945