Reduced reperfusion injury in muscle. A comparison of the timing of EPC-K1 administration in rats.
EPC-K1, a phosphate diester of alpha-tocopherol and ascorbic acid, is a new hydroxyl radical scavenger. We examined the effects of EPC-K1 according to differences in the timing of its administration. Warm ischemia, produced by vascular pedicle clamping, was sustained for 4 hours. After 24 hours of reperfusion, muscle injury was evaluated in 4 groups: the first group received a sham operation, the second group was treated with an intravenous injection of EPC-K1 prior to ischemia, the third group was treated with EPC-K1 prior to reperfusion, and the fourth group was controls. Compared with the control group, both the preischemic and pre-reperfusion EPC-K1-treated groups showed a statistically significant amelioration in the reduction of isometric muscle contraction. There were also significant reductions in the muscle and serum levels of thiobarbituric acid reactive substances (TBA-RS) and muscle damage, indicated by the biochemical and histological study. A comparison of the timing of EPC-K1 administration revealed that only the muscle TBA-RS level in the pre-reperfusion EPC-K1-treated group was significantly higher than that in the preischemic EPC-K1-treated group. These observations indicate that EPC-K1 not only by preischemic but also by pre-reperfusion administration acted effectively on reperfusion injury in muscle, thereby improving muscle function.
Hirose
J
J
Department of Orthopedic Surgery, Kumamoto University School of Medicine, Japan.
Yamaga
M
M
Takagi
K
K
D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage*; D001205:Ascorbic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives*; D001706:Biopsy; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D004353:Drug Evaluation, Preclinical; D016166:Free Radical Scavengers / Q000627:therapeutic use*; D007275:Injections, Intravenous; D007511:Ischemia / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D007537:Isometric Contraction / Q000187:drug effects*; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000503:physiopathology; D011897:Random Allocation; D051381:Rats; D011917:Rats, Inbred Lew; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D013997:Time Factors; D014810:Vitamin E / Q000008:administration & dosage / Q000031:analogs & derivatives*
D000975:Antioxidants; D016166:Free Radical Scavengers; D017392:Thiobarbituric Acid Reactive Substances; D014810:Vitamin E; C066638:potassium ascorbyl tocopheryl phosphate; D001205:Ascorbic Acid