1. The Beneficial Effects of ETS-GS, a Novel Vitamin E Derivative, on a Rat Model of Crush Injury.
- Author
-
Nakagawa J, Matsumoto N, Nakane Y, Yamakawa K, Yamada T, Matsumoto H, Shimazaki J, Imamura Y, Ogura H, Jin T, and Shimazu T
- Subjects
- Animals, Disease Models, Animal, HMGB1 Protein blood, Interleukin-6 blood, Lung drug effects, Lung metabolism, Lung pathology, Male, Malondialdehyde blood, Rats, Rats, Wistar, Reactive Oxygen Species metabolism, Superoxide Dismutase metabolism, Crush Syndrome blood, Crush Syndrome drug therapy, Oligopeptides therapeutic use, Vitamin E analogs & derivatives
- 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.
- Published
- 2016
- Full Text
- View/download PDF