Nature Medicine
1, 154 - 158 (1995)
doi:10.1038/nm0295-154
Non-steroidal anti-inflammatory drugs (NSAIDs) associate with zwitterionic phospholipids: Insight into the mechanism and reversal of NSAID-induced gastrointestinal injuryLenard M. Lichtenberger1, 3, Zu-Mo Wang1, Jimmy J. Romero1, Carlos Ulloa1, Joseph C. Perez1, Marie-Noëlle Giraud1
& José C. Barreto2
1Department of Physiology and Cell Biology The University of Texas Medical School at Houston Houston, Texas 77030, USA
2Department of Surgery The University of Texas Medical School at Houston Houston, Texas 77030, USA
3Correspondence should be addressed to L.M.L. The molecular basis of the injurious actions of non-steroidal anti-inflammatory drugs (NSAIDs) on the gastrointestinal (GI) tract is only partly understood. In this study we have obtained evidence, employing both in vitro and in vivo systems, that five NSAIDs have the ability to form a chemical association with zwitterionic phospholipids. Since this same class of phospholipids line the luminal aspects of the mucus gel layer to provide it with non-wettable properties, this intermolecular association may be the mechanism by which NSAIDs attenuate the hydrophobic barrier properties of the upper GI tract. Preassociating a number of NSAIDs with exogenous zwitterionic phospholipids prevented this increase in surface wettability of the mucus gel layer and protected rats against the injurious GI side-effects of these drugs, while enhancing their lipid permeability, antipyretic and anti-inflammatory activity.
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