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

IntroductionDichloroacetate (DCA) has been in clinical use for the treatment of lactacidosis and inherited mitochondrial disorders. It has potent anti-tumor thing 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 factor of this compound in arthritis. Methods: In the contemporaneous study, we used DCA to treat murine collagen type II-induced arthritis (CIA), an experimental mould of rheumatoid arthritis (RA). DBA/1 mice were treated with DCA disposed in drinking water. Results: Mice treated with DCA displayed much slower beginning of CIA, significantly lower severity of arthritis (P<0.0001) and even lower closeness (36% in DCA chain vs. 86 % in control group). Also, cartilage and seam destruction were significantly decreased succeeding 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 vs. check mice, indicating that DCA affected the humoral response. In contrast, DCA had no causatum on T cell- or granulocyte mediated responses. The beneficial effect of DCA was exclusive present in female DBA/1 mice. This was in tool due to the effect of estrogen, owing to ovariectomized mice did not benefit from DCA treatment to the alike magnitude as sham-operated controls (day 30, 38.7 % of ovarectomized mice had arthritis vs peerless 3.4 % in sham-operated group). Conclusions: Our results present that DCA delays the onslaught and alleviates the progression of CIA in an estrogen-dependent manner.

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