Inhibition of xanthine oxidase reduces oxidative stress and improves skeletal muscle function in response to electrically stimulated isometric contractions in aged mice

Michael J. Ryan, Janna R. Jackson, Yanlei Hao, Stephen S. Leonard, Stephen Alway

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Oxidative stress is a putative factor responsible for reducing function and increasing apoptotic signaling in skeletal muscle with aging. This study examined the contribution and functional significance of the xanthine oxidase enzyme as a potential source of oxidant production in aged skeletal muscle during repetitive in situ electrically stimulated isometric contractions. Xanthine oxidase activity was inhibited in young adult and aged mice via a subcutaneously placed time-release (2.5 mg/day) allopurinol pellet, 7 days before the start of in situ electrically stimulated isometric contractions. Gastrocnemius muscles were electrically activated with 20 maximal contractions for 3 consecutive days. Xanthine oxidase activity was 65% greater in the gastrocnemius muscle of aged mice compared to young mice. Xanthine oxidase activity also increased after in situ electrically stimulated isometric contractions in muscles from both young (33%) and aged (28%) mice, relative to contralateral noncontracted muscles. Allopurinol attenuated the exercise-induced increase in oxidative stress, but it did not affect the elevated basal level of oxidative stress that was associated with aging. In addition, inhibition of xanthine oxidase activity decreased caspase-3 activity, but it had no effect on other markers of mitochondrial-associated apoptosis. Our results show that compared to control conditions, suppression of xanthine oxidase activity by allopurinol reduced xanthine oxidase activity, H 2O 2 levels, lipid peroxidation, and caspase-3 activity; prevented the in situ electrically stimulated isometric contraction-induced loss of glutathione; prevented the increase in catalase and copper-zinc superoxide dismutase activities; and increased maximal isometric force in the plantar flexor muscles of aged mice after repetitive electrically evoked contractions.

Original languageEnglish (US)
Pages (from-to)38-52
Number of pages15
JournalFree Radical Biology and Medicine
Volume51
Issue number1
DOIs
StatePublished - Jul 1 2011
Externally publishedYes

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Isometric Contraction
Oxidative stress
Xanthine Oxidase
Muscle
Skeletal Muscle
Oxidative Stress
Allopurinol
Caspase 3
Muscles
Aging of materials
Oxidants
Catalase
Lipid Peroxidation
Superoxide Dismutase
Glutathione
Zinc
Copper
Young Adult
Exercise
Apoptosis

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Physiology (medical)

Cite this

Inhibition of xanthine oxidase reduces oxidative stress and improves skeletal muscle function in response to electrically stimulated isometric contractions in aged mice. / Ryan, Michael J.; Jackson, Janna R.; Hao, Yanlei; Leonard, Stephen S.; Alway, Stephen.

In: Free Radical Biology and Medicine, Vol. 51, No. 1, 01.07.2011, p. 38-52.

Research output: Contribution to journalArticle

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