Dichloroacetate ameliorates apoptosis, EMT and oxidative stress in diabetic cataract via inhibiting the IDO1-dependent p38 MAPK pathway.

As an oral antidiabetic agent, dichloroacetate (DCA) has been proven to improve diabetes and related complications. However, its functional role in diabetic cataract (DC) remains to be elucidated. This study was to define the role of DCA and its underlying molecular mechanism in DC in vitro and in vivo. In this study, it was shown that DCA dose-dependently ameliorated DC formation and development in DM rats. In addition, DCA significantly increased cell viability, reduced apoptosis, and inhibited EMT and oxidative stress of high glucose (HG)-treated SRA-01/04 cells in a concentration-dependent manner. Besides, it was revealed that Indoleamine 2,3-dioxygenase 1 (IDO1) expression was upregulated in lenses of DM rats and HG-treated SRA-01/04 cells, which was reversed by DCA. In addition, DCA abrogated the activation of the p38 MAPK signaling in the lenses of DM rats and HG-treated SRA-01/04 cells. Further experiments showed that IDO1 upregulation activated the p38 MAPK signaling in HG-challenged SRA-01/04 cells. Moreover, IDO1 overexpression partially reversed DCA-mediated inactivation of p38 MAPK signaling and suppression of HG-induced damage to SRA-01/04 cells. To sum up, our findings showed that DCA prevented DC-related apoptosis, EMT, and oxidative stress via inactivating IDO1-dependent p38 MAPK signaling.