title: Muscle dysfunction associated with adjuvant-induced arthritis is prevented by antioxidant treatment.
abstract: BACKGROUND
  In addition to the primary symptoms arising from inflamed joints, muscle weakness is prominent and frequent in patients with rheumatoid arthritis (RA). Here, we investigated the mechanisms of arthritis-induced muscle dysfunction in rats with adjuvant-induced arthritis (AIA).
  
  
  METHODS
  AIA was induced in the knees of rats by injection of complete Freund's adjuvant and was allowed to develop for 21 days. Muscle contractile function was assessed in isolated extensor digitorum longus (EDL) muscles. To assess mechanisms underlying contractile dysfunction, we measured redox modifications, redox enzymes and inflammatory mediators, and activity of actomyosin ATPase and sarcoplasmic reticulum (SR) Ca(2+)-ATPase.
  
  
  RESULTS
  EDL muscles from AIA rats showed decreased tetanic force per cross-sectional area and slowed twitch contraction and relaxation. These contractile dysfunctions in AIA muscles were accompanied by marked decreases in actomyosin ATPase and SR Ca(2+)-ATPase activities. Actin aggregates were observed in AIA muscles, and these contained high levels of 3-nitrotyrosine and malondialdehyde-protein adducts. AIA muscles showed increased protein expression of NADPH oxidase 2/gp91(phox), neuronal nitric oxide synthase, tumor necrosis factor α (TNF-α), and high-mobility group box 1 (HMGB1). Treatment of AIA rats with EUK-134 (3 mg/kg/day), a superoxide dismutase/catalase mimetic, prevented both the decrease in tetanic force and the formation of actin aggregates in EDL muscles without having any beneficial effect on the arthritis development.
  
  
  CONCLUSIONS
  Antioxidant treatment prevented the development of oxidant-induced actin aggregates and contractile dysfunction in the skeletal muscle of AIA rats. This implies that antioxidant treatment can be used to effectively counteract muscle weakness in inflammatory conditions.
authors.affiliation: Graduate School of Health Sciences, Sapporo Medical University, South 1 West 17, Chuo-ku, 060-8556, Sapporo Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Yamada
authors.affiliation: Graduate School of Health Sciences, Sapporo Medical University, South 1 West 17, Chuo-ku, 060-8556, Sapporo Japan.
authors.forename: Masami
authors.initials: M
authors.lastname: Abe
authors.affiliation: Graduate School of Health Sciences, Sapporo Medical University, South 1 West 17, Chuo-ku, 060-8556, Sapporo Japan.
authors.forename: Jaesik
authors.initials: J
authors.lastname: Lee
authors.affiliation: Graduate School of Health Sciences, Sapporo Medical University, South 1 West 17, Chuo-ku, 060-8556, Sapporo Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Tatebayashi
authors.affiliation: Graduate School of Health Sciences, Sapporo Medical University, South 1 West 17, Chuo-ku, 060-8556, Sapporo Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Himori
authors.affiliation: Faculty of Food Culture, Kurashiki Sakuyo University, 3515 Nagao-Tamashima, Kurashiki, Japan.
authors.forename: Keita
authors.initials: K
authors.lastname: Kanzaki
authors.affiliation: Graduate School of Integrated Arts and Sciences, Hiroshima University, 1-7-1, Higashi, Hiroshima Japan.
authors.forename: Masanobu
authors.initials: M
authors.lastname: Wada
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institutet, SE-17177 Stockholm, Sweden.
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Bruton
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institutet, SE-17177 Stockholm, Sweden.
authors.forename: Håkan
authors.initials: H
authors.lastname: Westerblad
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institutet, SE-17177 Stockholm, Sweden.
authors.forename: Johanna T
authors.initials: JT
authors.lastname: Lanner
keywords: Aggregation; Antioxidant; Muscle weakness; Rheumatoid arthritis