Oxypurinol administration fails to prevent free radical-mediated lipid peroxidation during loaded breathing

G. Supinski, D. Nethery, D. Stofan, L. Szweda, A. DiMarco

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


The purpose of the present study was to determine whether it is possible to alter the development of fatigue and ablate free radical-mediated lipid peroxidation of the diaphragm during loaded breathing by administering oxypurinol, a xanthine oxidase inhibitor. We studied 1) room-air-breathing decerebrate, unanesthetized rats given either saline or oxypurinol (50 mg/kg) and loaded with a large inspiratory resistance until airway pressure had fallen by 50% and 2) unloaded saline- and oxypurinol-treated room-air- breathing control animals. Additional sets of studies were performed with animals breathing 100% oxygen. Animals were killed at the conclusion of loading, and diaphragmatic samples were obtained for determination of thiobarbituric acid-reactive substances and assessment of in vitro force generation. We found that loading of saline-treated animals resulted in significant diaphragmatic fatigue and thiobarbituric acid-reactive substances formation (P < 0.01). Oxypurinol administration, however, failed to increase load trial time, reduce fatigue development, or prevent lipid peroxidation in either room-air-breathing or oxygen-breathing animals. These data suggest that xanthine oxidase-dependent pathways do not generate physiologically significant levels of free radicals during the type of inspiratory resistive loading examined in this study.

Original languageEnglish
Pages (from-to)1123-1131
Number of pages9
JournalJournal of Applied Physiology
Issue number3
StatePublished - Sep 1999


  • Diaphragm
  • Free radicals
  • Respiratory muscles
  • Skeletal muscle

ASJC Scopus subject areas

  • General Medicine


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