title: Effects of capsaicin on cellular damage and monolayer permeability in human intestinal Caco-2 cells.
abstract: Recent studies suggest that capsaicin (Cap), a major constituent of hot pepper, may affect the function and permeability of the intestinal mucosa in vitro. However, the relationships between the dose of Cap and the barrier and/or transporter functions on intestinal epithelial cells are unknown. The aim of this study was to investigate whether Cap initiates cellular injury and alter epithelial permeability in Caco-2 cells. Cellular toxicity, as measured using a lactate dehydrogenase release assay, was not observed at high concentrations of Cap (up to 300 microM). When cell viability was measured by a WST-1 assay (tetrazolium salt-based assay), damage to Caco-2 monolayers was observed at doses of 200 and 300 microM of Cap. The barrier function of tight junctions was assessed by measuring transepithelial electrical resistance (TEER) in Caco-2 cells. Treatment of Caco-2 cells with Cap at doses above 100 microM significantly decreased the TEER compared to treatment with buffer alone for 2 h (p<0.05). We next examined the effects of Cap on the activity of P-glycoprotein (P-gp) found on transcellular transporters. At doses of 100 and 200 microM, Cap inhibited the transport of rhodamine 123 by P-gp-mediated efflux in Caco-2 cells. Cap thus exhibited inhibitory effects on P-gp. The results of this study indicate that Cap, a dietary phytochemical, causes functional and structural changes in Caco-2 cell monolayers at noncytotoxic doses (less than 100 microM of Cap). The concomitant administration of Cap with drugs that are substrates of P-gp might increase the plasma concentrations of such drugs.
authors.affiliation: Laboratory of Clinical Pharmacy & Clinical Pharmacokinetics, Osaka University of Pharmaceutical Sciences, Takatsuki, Japan.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Tsukura
authors.forename: Maya
authors.initials: M
authors.lastname: Mori
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Hirotani
authors.forename: Kenji
authors.initials: K
authors.lastname: Ikeda
authors.forename: Fumio
authors.initials: F
authors.lastname: Amano
authors.forename: Ryuji
authors.initials: R
authors.lastname: Kato
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Ijiri
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Tanaka
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D018938:Caco-2 Cells; D002211:Capsaicin / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects* / Q000648:ultrastructure; D002463:Cell Membrane Permeability / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004396:Coloring Agents; D003627:Data Interpretation, Statistical; D017097:Electric Impedance; D020895:Enterocytes / Q000187:drug effects; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D004364:Pharmaceutical Preparations / Q000378:metabolism; D020112:Rhodamine 123; D013778:Tetrazolium Salts; D019108:Tight Junctions / Q000187:drug effects
chemical_list: C110656:2-(4-iodophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D004396:Coloring Agents; D004364:Pharmaceutical Preparations; D013778:Tetrazolium Salts; D020112:Rhodamine 123; D007770:L-Lactate Dehydrogenase; D002211:Capsaicin