Intravenous administration of thioredoxin decreases brain damage following transient focal cerebral ischemia in mice

• Published in: Antioxidants & redox signaling Vol. 6; no. 1; p. 81
• Main Authors: Hattori, Itaro, Takagi, Yasushi, Nakamura, Hajime, Nozaki, Kazuhiko, Bai, Jie, Kondo, Norihiko, Sugino, Toshiyuki, Nishimura, Masaki, Hashimoto, Nobuo, Yodoi, Junji
• Format: Journal Article
• Language: English
• Published: United States 01.02.2004
• Subjects: Animals; Brain - drug effects; Brain - metabolism; Brain - pathology; Brain Infarction - pathology; Brain Infarction - prevention & control; Disease Models, Animal; Dose-Response Relationship, Drug; Humans; Injections, Intravenous; Ischemic Attack, Transient - drug therapy; Ischemic Attack, Transient - metabolism; Ischemic Attack, Transient - pathology; Male; Mice; Mice, Inbred C57BL; Mitogen-Activated Protein Kinases - drug effects; Mitogen-Activated Protein Kinases - metabolism; Oxidation-Reduction - drug effects; p38 Mitogen-Activated Protein Kinases; Proteins - metabolism; Recombinant Proteins - therapeutic use; Thioredoxins - therapeutic use
• ISSN: 1523-0864
• DOI: 10.1089/152308604771978372

Thioredoxin (TRX) is induced by a variety of oxidative stimuli and shows cytoprotective roles against oxidative stress. To clarify the possibility of clinical application, we examined the effects of intravenously administered TRX in a model of transient focal cerebral ischemia in this study. Mature male C57BL/6j mice received either continuous intravenous infusion of recombinant human TRX (rhTRX) over a range of 1-10 mg/kg, bovine serum albumin, or vehicle alone for 2 h after 90-min transient middle cerebral artery occlusion (MCAO). Twenty-four hours after the transient MCAO, the animals were evaluated neurologically and the infarct volumes were assessed. Infarct volume, neurological deficit, and protein carbonyl contents, a marker of protein oxidation, in the brain were significantly ameliorated in rhTRX-treated mice at the dose of 3 and 10 mg/kg versus these parameters in control animals. Moreover, activation of p38 mitogen-activated protein kinase, whose pathway is involved in ischemic neuronal death, was suppressed in the rhTRX-treated mice. Further, rhTRX was detected in the ischemic hemisphere by western blot analysis, suggesting that rhTRX was able to permeate the blood-brain barrier in the ischemic hemisphere. These data indicate that exogenous TRX exerts distinct cytoprotective effects on cerebral ischemia/reperfusion injury in mice by means of its redox-regulating activity.