title: The Beneficial Effects of ETS-GS, a Novel Vitamin E Derivative, on a Rat Model of Crush Injury.
abstract: Crush syndrome is a devastating condition leading to multiple organ failure. The mechanisms by which local traumatic injuries affect distant organs remain unknown. ETS-GS is a novel water-soluble, stable anti-oxidative agent composed of vitamin E derivative. Given that one of the main pathophysiological effects in crush syndrome is massive ischemia-reperfusion, reactive oxygen species (ROS) generated from the injured extremities would be systemically involved in distant organ damage. We investigated whether ETS-GS could suppress inflammatory response and improve mortality in a rat model of crush injury. Crush injury was induced by compression of bilateral hindlimbs for 6 h followed by release of compression. Seven-day survival was significantly improved by ETS-GS treatment. To estimate anti-oxidative and anti-inflammatory effects of ETS-GS, serum was collected 6 and 20 h after the injury. ETS-GS treatment significantly dampened the up-regulation of malondialdehyde and reduction of superoxide dismutase in the serum, which were induced by crush injury. Serum levels of interleukin 6 and high mobility group box 1 were significantly decreased in the ETS-GS group compared with those in the control group. Lung damage shown by hematoxylin-eosin staining at 20 h after the injury was ameliorated by the treatment. Ex vivo imaging confirmed that ETS-GS treatment reduced ROS generation in both the lung and the muscle following crush injury. The administration of ETS-GS could suppress ROS generation, systemic inflammation, and the subsequent organ damage, thus improving survival in a rat model of crush injury. These findings suggest that ETS-GS can become a novel therapeutic agent against crush injury.
authors.affiliation: *Department of Traumatology and Acute Critical Medicine, Osaka University Graduate School of Medicine, Osaka, Japan †Laboratory for Nano-Bio Probes Quantitative Biology Center, Riken, Osaka, Japan.
authors.forename: Junichiro
authors.initials: J
authors.lastname: Nakagawa
authors.forename: Naoya
authors.initials: N
authors.lastname: Matsumoto
authors.forename: Yuko
authors.initials: Y
authors.lastname: Nakane
authors.forename: Kazuma
authors.initials: K
authors.lastname: Yamakawa
authors.forename: Tomoki
authors.initials: T
authors.lastname: Yamada
authors.forename: Hisatake
authors.initials: H
authors.lastname: Matsumoto
authors.forename: Junya
authors.initials: J
authors.lastname: Shimazaki
authors.forename: Yukio
authors.initials: Y
authors.lastname: Imamura
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ogura
authors.forename: Takashi
authors.initials: T
authors.lastname: Jin
authors.forename: Takeshi
authors.initials: T
authors.lastname: Shimazu
mesh_terms: D000818:Animals; D003444:Crush Syndrome / Q000097:blood* / Q000188:drug therapy*; D004195:Disease Models, Animal; D024243:HMGB1 Protein / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D009842:Oligopeptides / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D014810:Vitamin E / Q000031:analogs & derivatives*
chemical_list: D024243:HMGB1 Protein; D015850:Interleukin-6; D009842:Oligopeptides; D017382:Reactive Oxygen Species; C568419:gamma-L-glutamyl-S-(2-(((3,4-dihydro-2,5,7,8-tetramethyl-2-(4,8,12- trimethyltridecyl)-2H-1-benzopyran-6-yl)oxy)carbonyl)-3-oxo-3-((2-sulfoethyl)amino)propyl)-L-cysteinylglycine sodium salt; D014810:Vitamin E; D008315:Malondialdehyde; D013482:Superoxide Dismutase