Effects of a hydroxyl radical scavenger, EPC-K1, and neutrophil depletion on reperfusion injury in rat skeletal muscle.
Oxygen free radicals (OFR) and neutrophils are potent sources of reperfusion injury. We compared the effect of EPC-K1, a new OFR scavenger, and neutrophil depletion on the reperfusion injury in skeletal muscle, using an ischemic revascularized hindlimb model in rats. Warm ischemia, produced by vascular pedicle clamping, was sustained for 4 h. After 24 h of reperfusion, muscle function and damage were evaluated in 4 groups: a sham operation group, a control study group, a group treated by EPC-K1 (EPC group), and a group that received nitrogen mustard to induce neutropenia (NM group). Both the EPC and NM groups had limited muscle damage compared to the control group. The EPC group preserved muscle function significantly better than the control group and the mean isometric tetanic tension in the EPC group appeared to be higher than that in the NM group. Furthermore, levels of lipid peroxides in muscle and serum, and muscle edema in the EPC group, were significantly lower than in the NM group. Histological examinations supported these results. These findings suggest that limiting OFR generation by EPC-K1 in the early phase of reoxygenation is more potent than depletion of neutrophils in reducing reperfusion injury.
Hirose
J
J
Department of Orthopaedic Surgery, Kumamoto University School of Medicine, Japan. hirojun@mcw.edu
Yamaga
M
M
Kato
T
T
Ikebe
K
K
Takagi
K
K
D000818:Animals; D001205:Ascorbic Acid / Q000031:analogs & derivatives* / Q000737:chemistry / Q000276:immunology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D016166:Free Radical Scavengers / Q000737:chemistry / Q000276:immunology / Q000627:therapeutic use*; D007537:Isometric Contraction / Q000187:drug effects; D007958:Leukocyte Count; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D018482:Muscle, Skeletal / Q000293:injuries*; D009503:Neutropenia / Q000097:blood / Q000209:etiology*; D009504:Neutrophils / Q000187:drug effects; D011897:Random Allocation; D051381:Rats; D011917:Rats, Inbred Lew; D015427:Reperfusion Injury / Q000150:complications / Q000188:drug therapy* / Q000276:immunology* / Q000378:metabolism; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000737:chemistry / Q000276:immunology / Q000627:therapeutic use*
D016166:Free Radical Scavengers; D014810:Vitamin E; C066638:potassium ascorbyl tocopheryl phosphate; D001205:Ascorbic Acid