Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2487143 | Journal of Pharmaceutical Sciences | 2009 | 15 Pages |
Abstract
The present study investigates the effects of ethanol and hydrogen peroxide (H2O2) on the barrier function and prostaglandin E2 (PGE2) release in differentiated Cacoâ2 cells. Epithelial barrier integrity was estimated by measuring transepithelial electrical resistance (TEER), the transport of reference compounds and lactate dehydrogenase leakage, the PGE2 release by enzyme immunoassay. Ethanol and H2O2 decreased TEER and increased the transport of lucifer yellow without affecting that of propranolol and phenylalanine. Only the effects of ethanol were accompanied by PGE2 production and were reversible without causing longâterm cytotoxicity. The cyclooxygenaseâ2 inhibitor, NSâ398, prevented the effect of ethanol on both PGE2 release and TEER, while inhibition of both cyclooxygenaseâ2 and tyrosine kinase drastically compromised cell viability and TEER recovery. Hepatocyte growth factor, keratinocyte growth factor or insulin prevented the effect of ethanol on cell permeability, but not on PGE2 release. Their combination prevented the effect of H2O2. In conclusion, ethanol and H2O2 increased paracellular permeability in differentiated Cacoâ2 cells without affecting transcellular and active transport. Cyclooxygenaseâ2 stimulated PGE2 release mediated the reversible effect of ethanol on tight junctions and, meanwhile, contributed to cell survival. Growth factors, normally present in the intestine, exerted a selective protective effect toward paracellular permeability increase induced by irritants. © 2008 WileyâLiss, Inc. and the American Pharmacists Association J Pharm Sci 98:713-727, 2009
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Authors
RoseâMarie Catalioto, Carla Festa, Antonio Triolo, Maria Altamura, Carlo Alberto Maggi, Sandro Giuliani,