title: Dichloroacetate alleviates development of collagen II-induced arthritis in female DBA/1 mice.
abstract: BACKGROUND
  Dichloroacetate (DCA) has been in clinical use for the treatment of lactacidosis and inherited mitochondrial disorders. It has potent anti-tumor effects both in vivo and in vitro, facilitating apoptosis and inhibiting proliferation. The pro-apoptotic and anti-proliferative properties of DCA prompted us to investigate the effects of this compound in arthritis.
  
  
  METHODS
  In the present study, we used DCA to treat murine collagen type II (CII)-induced arthritis (CIA), an experimental model of rheumatoid arthritis. DBA/1 mice were treated with DCA given in drinking water.
  
  
  RESULTS
  Mice treated with DCA displayed much slower onset of CIA and significantly lower severity (P < 0.0001) and much lower frequency (36% in DCA group vs. 86% in control group) of arthritis. Also, cartilage and joint destruction was significantly decreased following DCA treatment (P = 0.005). Moreover, DCA prevented arthritis-induced cortical bone mineral loss. This clinical picture was also reflected by lower levels of anti-CII antibodies in DCA-treated versus control mice, indicating that DCA affected the humoral response. In contrast, DCA had no effect on T cell- or granulocyte-mediated responses. The beneficial effect of DCA was present in female DBA/1 mice only. This was due in part to the effect of estrogen, since ovariectomized mice did not benefit from DCA treatment to the same extent as sham-operated controls (day 30, 38.7% of ovarectomized mice had arthritis vs. only 3.4% in sham-operated group).
  
  
  CONCLUSIONS
  Our results indicate that DCA delays the onset and alleviates the progression of CIA in an estrogen-dependent manner.
authors.affiliation: Department of Rheumatology and Inflammation Research, Sahlgrenska Academy, University of Gothenburg, Guldhedsgatan 10A, Box 480, SE-405 30, Gothenburg, Sweden. li.bian@rheuma.gu.se
authors.forename: Li
authors.initials: L
authors.lastname: Bian
authors.forename: Elisabet
authors.initials: E
authors.lastname: Josefsson
authors.forename: Ing-Marie
authors.initials: IM
authors.lastname: Jonsson
authors.forename: Margareta
authors.initials: M
authors.lastname: Verdrengh
authors.forename: Claes
authors.initials: C
authors.lastname: Ohlsson
authors.forename: Maria
authors.initials: M
authors.lastname: Bokarewa
authors.forename: Andrej
authors.initials: A
authors.lastname: Tarkowski
authors.forename: Mattias
authors.initials: M
authors.lastname: Magnusson
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D001323:Autoantibodies / Q000097:blood / Q000187:drug effects; D015519:Bone Density / Q000187:drug effects; D003094:Collagen / Q000276:immunology; D003999:Dichloroacetic Acid / Q000627:therapeutic use*; D004967:Estrogens / Q000378:metabolism; D005260:Female; D006968:Hypersensitivity, Delayed / Q000188:drug therapy / Q000276:immunology; D051379:Mice; D008811:Mice, Inbred DBA; D010052:Ovariectomy; D013601:T-Lymphocytes / Q000187:drug effects
chemical_list: D001323:Autoantibodies; D004967:Estrogens; D003094:Collagen; D003999:Dichloroacetic Acid