title: A human serum albumin-thioredoxin fusion protein prevents experimental contrast-induced nephropathy.
abstract: Contrast-induced nephropathy (CIN), caused by a combination of the direct tubular toxicity of contrast media, a reduction in medullary blood flow, and the generation of reactive oxygen species, is a serious clinical problem. A need exists for effective strategies for its prevention. Thioredoxin-1 (Trx) is a low-molecular-weight endogenous redox-active protein with a short half-life in the blood due to renal excretion. We produced a long-acting form of Trx as a recombinant human albumin-Trx fusion protein (HSA-Trx) and examined its effectiveness in preventing renal injury in a rat model of ioversol-induced CIN. Compared with saline, a mixture of HSA and Trx, or Trx alone, intravenous HSA-Trx pretreatment significantly attenuated elevations in serum creatinine, blood urea nitrogen, and urinary N-acetyl-β-D-glucosaminidase along with the decrease in creatinine clearance. HSA-Trx also caused a substantial reduction in the histological features of renal tubular injuries and in the number of apoptosis-positive tubular cells. Changes in the markers 8-hydroxy deoxyguanosine and malondialdehyde indicated that HSA-Trx significantly suppressed renal oxidative stress. In HK-2 cells, HSA-Trx decreased the level of reactive oxygen species induced by hydrogen peroxide, and subsequently improved cell viability. Thus, our results suggest that due to its long-acting properties, HSA-Trx has the potential to effectively prevent CIN.
authors.affiliation: Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Chuo-ku, Kumamoto, Japan.
authors.forename: Azusa
authors.initials: A
authors.lastname: Kodama
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Watanabe
authors.forename: Ryota
authors.initials: R
authors.lastname: Tanaka
authors.forename: Hisae
authors.initials: H
authors.lastname: Tanaka
authors.forename: Victor T G
authors.initials: VT
authors.lastname: Chuang
authors.forename: Yohei
authors.initials: Y
authors.lastname: Miyamoto
authors.forename: Qiong
authors.initials: Q
authors.lastname: Wu
authors.forename: Masayuki
authors.initials: M
authors.lastname: Endo
authors.forename: Keisuke
authors.initials: K
authors.lastname: Hamasaki
authors.forename: Yu
authors.initials: Y
authors.lastname: Ishima
authors.forename: Masafumi
authors.initials: M
authors.lastname: Fukagawa
authors.forename: Masaki
authors.initials: M
authors.lastname: Otagiri
authors.forename: Toru
authors.initials: T
authors.lastname: Maruyama
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003287:Contrast Media / Q000633:toxicity*; D006801:Humans; D007674:Kidney Diseases / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control*; D007684:Kidney Tubules / Q000187:drug effects / Q000473:pathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use*; D012709:Serum Albumin / Q000627:therapeutic use*; D013879:Thioredoxins / Q000627:therapeutic use*
chemical_list: D003287:Contrast Media; D017382:Reactive Oxygen Species; D011993:Recombinant Fusion Proteins; D012709:Serum Albumin; D013879:Thioredoxins