Effects of ovariectomy and estrogen on ischemia-reperfusion injury in hindlimbs of female rats.
The effects of estrogen and ovariectomy on indexes of muscle damage after 2 h of complete hindlimb ischemia and 2 h of reperfusion were investigated in female Sprague-Dawley rats. The rats were assigned to one of three experimental groups: ovariectomized with a 17beta-estradiol pellet implant (OE), ovariectomized with a placebo pellet implant (OP), or control with intact ovaries (R). It was hypothesized that following ischemia-reperfusion (I/R), muscle damage indexes [serum creatine kinase (CK) activity, calpain-like activity, inflammatory cell infiltration, and markers of lipid peroxidation (thiobarbituric-reactive substances)] would be lower in the OE and R rats compared with the OP rats due to the protective effects of estrogen. Serum CK activity following I/R was greater (P < 0.01) in the R rats vs. OP rats and similar in the OP and OE rats. Calpain-like activity was greatest in the R rats (P < 0.01) and similar in the OP and OE rats. Neutrophil infiltration was assessed using the myeloperoxidase (MPO) assay and immunohistochemical staining for CD43-positive (CD43+) cells. MPO activity was lower (P < 0.05) in the OE rats compared with any other group and similar in the OP and R rats. The number of CD43+ cells was greater (P < 0.01) in the OP rats compared with the OE and R rats and similar in the OE and R rats. The OE rats had lower (P < 0.05) thiobarbituric-reactive substance content following I/R compared with the R and OP rats. Indexes of muscle damage were consistently attenuated in the OE rats but not in the R rats. A 10-fold difference in serum estrogen content may mediate this. Surprisingly, serum CK activity and muscle calpain-like activity were lower (P < 0.05) in the OP rats compared with the R rats. Increases in serum insulin-like growth factor-1 content (P < 0.05) due to ovariectomy were hypothesized to account for this finding. Thus both ovariectomy and estrogen supplementation have differential effects on indexes of I/R muscle damage.
Stupka
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Department of Kinesiology and Physical Education, Wilfrid Laurier University, Waterloo, Ontario, Canada N2L 3C5.
Tiidus
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PM
D000818:Animals; D015703:Antigens, CD; D002154:Calpain / Q000378:metabolism; D003402:Creatine Kinase / Q000097:blood; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D006003:Glycogen / Q000378:metabolism; D006614:Hindlimb / Q000473:pathology*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D019344:Lactic Acid / Q000378:metabolism; D051917:Leukosialin; D015227:Lipid Peroxidation / Q000502:physiology; D018482:Muscle, Skeletal / Q000473:pathology; D020556:Neutrophil Infiltration / Q000502:physiology; D010052:Ovariectomy; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology; D012795:Sialoglycoproteins / Q000276:immunology; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D015703:Antigens, CD; D004967:Estrogens; D051917:Leukosialin; D012795:Sialoglycoproteins; C497864:Spn protein, rat; D017392:Thiobarbituric Acid Reactive Substances; D019344:Lactic Acid; D007334:Insulin-Like Growth Factor I; D006003:Glycogen; D009195:Peroxidase; D003402:Creatine Kinase; D002154:Calpain