Figure 8. Dichloroacetate (DCA) improves small intestinal villus structure and increases expression of the β-catenin anabolic transcription factor for cell and organ regeneration pathways.

(A) Small intestine sample from mice with cecal ligation and puncture (CLP) with vehicle or DCA were examined by light microscopy and assessed in a blinded fashion. Blunting of small intestinal villi occurred as expected after 30 hours of sepsis. CLP⁺ DCA mice showed improved structural features of the intestine, with a possible increase in villus length, vs. CLP⁺ vehicle group (A). To assess effects of DCA on organs and cells, we used organ and immune cell regeneration promoter β-catenin and compared CLP⁺ vehicle vs. CLP⁺ DCA treatment using IHC. β-Catenin immunofluorescence increased CLP⁺ DCA compared with CLP⁺ vehicle group in small intestine (B), liver (C), and kidney (D) tissue sections. To further examine this potential anabolic marker, we performed immunoblots in different tissues and cells in SHAM, CLP⁺ vehicle, and CLP⁺ DCA groups. β-Catenin expression decreased in CLP⁺ vehicle vs. SHAM in kidney and heart tissue samples (E). We also found in a human monocyte in vitro cell model of sepsis 24 hours after endotoxin tolerance development that 5 mM DCA increased β-catenin expression (E). IHC scale bar: 100 μm. n = 3 animals were studied in each cohort for each tissue using IHC. For immunoblots, n ≥ 2 experiments, and 1 exemplary experiment is shown for isolated hepatocytes, heart, and kidney tissue each. For THP-1 cells, 3 distinct in vitro experiments were performed, and 1 example is shown.