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ASGSB 2003 Annual Meeting Abstracts
[72]
RELEASED XANTHINE OXIDASE AS A CONTRIBUTING SOURCE FOR OXIDATIVE STRESS. D.A. von Deutsch1,2,4, I.K. Abukhalaf1,2,4, L.E. Wineski3, R.R. Socci2, A.W. von Deutsch1,5, M.A. Bayorh1,2, and N.A. Silvestrov2,4. 1Space Medicine and Life Sciences Research Center, Departments of: 2Pharmacology & Toxicology; 3Neurobiology and Anatomy; and the 4Clinical Research Center, Morehouse School of Medicine, Atlanta, GA 30310. 5Collins Hill High School, Lawrenceville, GA.
Mechanism(s) underlying readaptation-induced oxidative stress and damage are of concern for the space program. During recovery, astronauts are prone to injury through strenuous and eccentric movements, which are more pronounced in atrophied muscles. Hydrogen peroxide, a byproduct of xanthine/xanthine oxidase (XO) reaction, strips ferrous iron (Fe2+) from hemoglobin and released myoglobin. Subsequently, free Fe2+ reacts with peroxides, yielding hydroxyl radicals that can covalently bond with cellular macromolecules, cause lipid peroxidation, membrane damage, and cell death. The purpose of this work was to determine sources of oxidative stress in post-hindlimb suspended rats. XO activity and catecholamine (epinephrine [E], norepinephrine [NE]) levels were measured in plasma. To model post-flight readaptation to Earth, rats were initially subjected to two-weeks of hindlimb suspension and 0.5 or 24-hour post-suspension period where the rats were free to move about their cages. Plasma XO activity was determined in non-suspended control and post-suspended rats. Results show a direct linear correlation between plasma XO activity and catecholamine levels (XO:E, r= 0.987; XO:NE, r= 0.935) in non-suspended rats. However, in suspended rats, there was an inverse nonlinear relationship (XO:E, R2 = 0.977, r = -0.989; XO:NE, R2 = 0.921, r= -0.941). Mean XO activity levels in non-suspended and 24 hr post-suspended rats were 97.6 ± 14.9 and 178.0 ±31.2 mUnits/mL (p< 0.03), respectively. This suggests that during readaptation, the physical act of muscle reloading contributes to minor vascular and muscle damage and the release of xanthine oxidase.
(Supported by NASA Grant NCC9-112 and NIH Grants RCRII 2P20, RR11104-09, and 5P20RR11104-7)
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