Tranexamic acid inhibits mitochondrial DNA release and reduces inflammatory response in an in vitro model of OGD/R-induced Caco-2 cell injury

Ischemia-reperfusion (I/R) injury of the intestine remains a challenging clinical issue, and there is currently no definitive treatment protocol. Tranexamic acid (TXA), an antifibrinolytic drug used in bleeding patients, has been shown in previous studies to protect the intestinal epithelial barrier, but the specific mechanism remains unclear. This study aimed to explore the molecular mechanisms by which TXA protects the intestinal barrier after intestinal I/R. The cell viability assay was assessed to verify the cytotoxicity of TXA toward Caco-2 cells. A Caco-2 cell oxygen-glucose deprivation-reperfusion (OGD/R) model was established. The transepithelial electrical resistance (TEER) of Caco-2 cell monolayers and FITC-dextran permeability assays were performed to assess the intestinal barrier function. The JC-1 fluorescent probe was used for assessment of mitochondrial membrane potential. Quantitative PCR (qPCR) was used to quantify mitochondrial DNA (mtDNA) released by Caco-2 cells, and enzyme-linked immunosorbent assay (ELISA) was employed to assess inflammatory factors. TXA reversed OGD/R-induced decreases in TEER and increases in FITC-dextran permeability in Caco-2 cell monolayers. Microscopy images of the Caco-2 monolayer also support these results. Additionally, TXA enhanced mitochondrial membrane potential, suppressed mtDNA release and alleviated inflammatory responses. TXA protects the intestinal barrier after intestinal I/R by enhancing mitochondrial membrane potential, inhibiting mtDNA release and reducing inflammation, suggesting its potential as a therapeutic agent for intestinal I/R injury.