Enhanced bioaccessibility and transport of reduced coenzyme Q10 is dependent on GSH status in Caco‐2 human intestinal epithelial cells (1044.8)

Abstract

Recently, the bioavailability of orally administered reduced CoQ10 (CoQH) was reported to be markedly greater than that of oxidized CoQ10 (CoQ10) in healthy adults. We have investigated the basis for the influence of redox state on absorption using the coupled in vitro digestion/Caco‐2 cell model. Aliquots of CoQH and CoQ10 in hydrogenated castor oil were added to yogurt before simulated gastric and small intestinal digestion. Partitioning of CoQH in aqueous (i.e., bioaccessible) fraction of chyme was significantly greater than that of CoQ10. Similarly, when diluted bioaccessible fraction was added to the apical compartment of monolayers of Caco‐2 cells, uptake and trans‐epithelial transport of CoQH were 2.3 and 3.4 times greater than that of CoQ10, respectively. Reduction of cellular GSH significantly decreased both uptake and transport of CoQH and CoQ10 by Caco‐2 cells, although the extent of inhibition was much greater for CoQH. This suggests that maintaining a reduced intracellular environment is essential for efficient absorption of the CoQ. Auranofin‐mediated inhibition of thioredoxin reductase activity also decreased apical uptake and transport of CoQH, but not CoQ10. However, this differential effect was associated with auranofin‐associated oxidation and degradation of micellar CoQH in apical medium rather than changes in intracellular GSH status. These data suggest that the increased bioavailability of CoQH compared to CoQ10 results from its greater micellarization, more efficient uptake, and enhanced trans‐epithelial transport across the epithelial barrier, and that the cellular processes are dependent on a high ratio of GSH to GSSG for maintaining CoQ in the reduced state.