Effects of citrus fruit juices on cytotoxicity and drug transport pathways of Caco-2 cell monolayers.
The aim of this study was to correlate the taxonomy of grapefruit, pummelo, orange, lime and lemon with fruit juice-mediated cytotoxicity, modulation of epithelial permeability and P-glycoprotein (P-gp)-mediated efflux using 0-50% juice concentrations. Lime and lemon juices at 30% enhanced the absorption of [14C]-mannitol across Caco-2 cell monolayers by six- and eight-fold, respectively, but grapefruit and pummelo juices did not modulate the paracellular [14C]-mannitol transport even at 50%. Orange juice at 30% increased mannitol absorption to a comparable level as lime juice, but had minimal effects on TEER. All five juices did not modulate the passive diffusional pathway as exemplified by their negligible effects on [3H]-propranolol absorption. Grapefruit, pummelo and orange juices showed P-gp inhibitory activity by reducing rhodamine-123 (R-123) efflux and elevating R-123 cellular accumulation, but lime and lemon juices did not. Lime and lemon juices at >or=30% were cytotoxic towards Caco-2 cells. Grapefruit and pummelo juices at 10% did not affect Caco-2 cell viability, but they enhanced cell growth at concentrations of >or=30%. Orange juice increased cell viability only at lower concentrations. On the basis of these data, lime and lemon juices could be regarded as a group distinct from grapefruit and pummelo juices, while orange juice appeared to belong to a bridging group. This grouping was consistent with the categorization of the citrus fruits according to their dominant flavonoid pattern and taxonomy.
Lim
Siok-Lam
SL
Department of Pharmacy, National University of Singapore, 18 Science Drive 4, Singapore 117543, Singapore.
Lim
Lee-Yong
LY
D000042:Absorption; D001628:Beverages / Q000633:toxicity; D001692:Biological Transport / Q000187:drug effects; D018938:Caco-2 Cells; D002250:Carbon Radioisotopes; D002463:Cell Membrane Permeability / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002957:Citrus / Q000145:classification; D018565:Food-Drug Interactions; D006801:Humans; D008353:Mannitol / Q000378:metabolism; D011433:Propranolol / Q000378:metabolism
D002250:Carbon Radioisotopes; D008353:Mannitol; D011433:Propranolol