Dichloroacetate alleviates development of collagen II-induced arthritis in female DBA/1 mice.

Abstract

INTRODUCTION:

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).

CONCLUSION:

Our results indicate that DCA delays the onset and alleviates the progression of CIA in an estrogen-dependent manner.

• Authors: Li Bian, Elisabet Josefsson, Ing-Marie Jonsson, Margareta Verdrengh, Claes Ohlsson, Maria Bokarewa, Andrej Tarkowski, Mattias Magnusson
• Journal: Arthritis research & therapy (Arthritis Res Ther) Vol. 11 Issue 5 Pg. R132 ( 2009) ISSN: 1478-6362 [Electronic] England
• PMID: 19723321 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Autoantibodies
• Estrogens
• Collagen
• Dichloroacetic Acid

Topics

• Animals
• Arthritis, Experimental (immunology, pathology, prevention & control)
• Arthritis, Rheumatoid (drug therapy, immunology, pathology)
• Autoantibodies (blood, drug effects)
• Bone Density (drug effects)
• Collagen (immunology)
• Dichloroacetic Acid (therapeutic use)
• Estrogens (metabolism)
• Female
• Hypersensitivity, Delayed (drug therapy, immunology)
• Mice
• Mice, Inbred DBA
• Ovariectomy
• T-Lymphocytes (drug effects)