Xanthine oxidase and activated neutrophils cause oxidative damage to skeletal muscle after contractile claudication.
We previously showed oxidative damage and edema within skeletal muscle after contractile claudication. To investigate the sources of this oxidative damage in the gastrocnemius muscle, we administered allopurinol (Allo, to inhibit xanthine oxidase) and cyclophosphamide (Cyclo, to deplete neutrophils) before inducing contractile claudication in male Sprague Dawley rats. Contractile claudication (ligated stimulated, LS) caused a significant increase in xanthine oxidase activity [sham ligated stimulated (SS) = 2.57 +/- 0.07; LS = 3.22 +/- 0.07] and neutrophil infiltration (SS = 0.47 +/- 0.03; LS = 0.91 +/- 0.10) compared with controls (SS), and this was associated with increased lipid peroxidation, protein oxidation, muscle damage, and edema. Pretreatment with Allo attenuated the increase in xanthine oxidase activity and attenuated lipid hydroperoxides (control LS = 12.85 +/- 0.50; Allo LS = 9.96 +/- 0.71), muscle damage, and neutrophil infiltration (control LS = 0.91 +/- 0.10; Allo LS = 0.61 +/- 0.07). This latter finding suggests that xanthine oxidase-derived oxidants are chemotactic to neutrophils. Pretreatment with Cyclo reduced neutrophil infiltration (control LS = 0.91 +/- 0.10; Cyclo LS = 0.55 +/- 0.02) and attenuated lipid peroxidation (control LS = 12.85 +/- 0.50; Cyclo LS = 6.462 +/- 0.62), protein oxidation (control LS = 2.59 +/- 0.47; Cyclo LS = 1.77 +/- 0.60), muscle damage, and edema. Together, these data indicate that contractile claudication causes an increase in xanthine oxidase activity and neutrophils in muscle and that inhibition of these oxidant sources protects against oxidative stress, muscle damage, and edema.
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PO Box 118205, University of Florida, Gainesville, FL 32611, USA.
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D000818:Animals; D007383:Intermittent Claudication / Q000503:physiopathology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D015227:Lipid Peroxidation; D008297:Male; D009119:Muscle Contraction / Q000502:physiology*; D009124:Muscle Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000502:physiology*; D018375:Neutrophil Activation / Q000502:physiology*; D009504:Neutrophils / Q000502:physiology; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology*; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014969:Xanthine Oxidase / Q000378:metabolism*
D009124:Muscle Proteins; D007770:L-Lactate Dehydrogenase; D009195:Peroxidase; D014969:Xanthine Oxidase