title: Therapeutic impact of human serum albumin-thioredoxin fusion protein on influenza virus-induced lung injury mice.
abstract: Reactive oxygen species (ROS) are the primary pathogenic molecules produced in viral lung infections. We previously reported on the use of a recombinant human serum albumin (HSA)-thioredoxin 1 (Trx) fusion protein (HSA-Trx) for extending the half-life Trx, an endogenous protein with anti-oxidant properties. As a result, it was possible to overcome the unfavorable pharmacokinetic and short pharmacological properties of Trx. We hypothesized that HSA-Trx would attenuate the enhanced ROS production of species such as hydroxyl radicals by neutrophils during an influenza viral infection. The levels of 8-hydroxy-2'-deoxyguanosine and 3-nitrotyrosine were used as indices of the anti-oxidant activity of HSA-Trx. In addition, the cytoprotective effects of HSA-Trx were examined in PR8 (H1N1) influenza virus-induced lung injured mice. The findings show that HSA-Trx reduced the number of total cells, neutrophils, and total protein in BALF of influenza virus-induced lung injured mice. The HSA-Trx treatment significantly decreased the level of 8-hydroxy-2'-deoxyguanosine and 3-nitrotyrosine, but failed to inhibit inducible nitric oxide synthase expression, in the lungs of the virus-infected mice. On the other hand, Tamiflu(®) treatment also significantly suppressed the production of inflammatory cells and neutrophil infiltration, as well as the protein level in BALF and lung histopathological alterations caused by the influenza virus. The suppressive effect of Tamiflu(®) was slightly stronger than that of HSA-Trx. Interestingly, Tamiflu(®) significantly decreased virus proliferation, while HSA-Trx had no effect. These results indicate that HSA-Trx may be of therapeutic value for the treatment of various acute inflammatory disorders such as influenza-virus-induced pneumonia, by inhibiting inflammatory-cell responses and suppressing the overproduction of NO in the lung.
authors.affiliation: Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University , Kumamoto , Japan.
authors.forename: Ryota
authors.initials: R
authors.lastname: Tanaka
authors.affiliation: Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University , Kumamoto , Japan ; Center for Clinical Pharmaceutical Sciences, School of Pharmacy, Kumamoto University , Kumamoto , Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Ishima
authors.affiliation: Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University , Kumamoto , Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Enoki
authors.affiliation: The Chemo-Sero-Therapeutic Research Institute (KAKETSUKEN) , Kumamoto , Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Kimachi
authors.affiliation: The Chemo-Sero-Therapeutic Research Institute (KAKETSUKEN) , Kumamoto , Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Shirai
authors.affiliation: Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University , Kumamoto , Japan ; Center for Clinical Pharmaceutical Sciences, School of Pharmacy, Kumamoto University , Kumamoto , Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Watanabe
authors.affiliation: Curtin Health Innovation Research Institute, School of Pharmacy, Faculty of Health Sciences, Curtin University , Perth, WA , Australia.
authors.forename: Victor T G
authors.initials: VT
authors.lastname: Chuang
authors.affiliation: Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University , Kumamoto , Japan ; Center for Clinical Pharmaceutical Sciences, School of Pharmacy, Kumamoto University , Kumamoto , Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Maruyama
authors.affiliation: Faculty of Pharmaceutical Sciences, Sojo University , Kumamoto , Japan ; DDS Research Institute, Sojo University , Kumamoto , Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Otagiri
keywords: albumin; anti-oxidization; fusion; influenza virus; thioredoxin