Clinical Research
Copyright ©The Author(s) 2005. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jul 14, 2005; 11(26): 4052-4060
Published online Jul 14, 2005. doi: 10.3748/wjg.v11.i26.4052
Lansoprazole prevents experimental gastric injury induced by non-steroidal anti-inflammatory drugs through a reduction of mucosal oxidative damage
Corrado Blandizzi, Matteo Fornai, Rocchina Colucci, Gianfranco Natale, Valter Lubrano, Cristina Vassalle, Luca Antonioli, Gloria Lazzeri, Mario Del Tacca
Corrado Blandizzi, Matteo Fornai, Rocchina Colucci, Mario Del Tacca, Division of Pharmacology and Chemotherapy, Department of Oncology, Transplants and Advanced Technologies in Medicine, University of Pisa, Pisa, Italy
Gianfranco Natale, Gloria Lazzeri, Department of Human Morphology and Applied Biology University of Pisa, Pisa, Italy
Valter Lubrano, Cristina Vassalle, Luca Antonioli, Institute of Clinical Physiology, National Research Council, Pisa, Italy
Author contributions: All authors contributed equally to the work.
Correspondence to: Professor Mario Del Tacca, MD, Division of Pharmacology and Chemotherapy, Department of Oncology, Transplants and Advanced Technologies in Medicine University of Pisa, Via Roma, 55- I-56126 Pisa, Italy. m.deltacca@med.unipi.it
Telephone: +39-50-830148 Fax: +39-50-562020
Received: July 17, 2004
Revised: November 1, 2004
Accepted: November 4, 2004
Published online: July 14, 2005
Abstract

AIM: This study investigated the mechanisms of protection afforded by the proton pump inhibitor lansoprazole against gastric injury induced by different non-steroidal anti-inflammatory drugs (NSAIDs) in rats.

METHODS: Male Sprague-Dawley rats were orally treated with indomethacin (100 µmol/kg), diclofenac (60 µmol/kg), piroxicam (150 µmol/kg) or ketoprofen (150 µmol/kg). Thirty minutes before NSAIDs, animals were orally treated with lansoprazole 18 or 90 µmol/kg. Four hours after the end of treatments, the following parameters were assessed: gastric mucosal PGE2, malondialdehyde (MDA), myeloperoxidase (MPO) or non-proteic sulfhydryl compounds (GSH) levels; reverse transcription-polymerase chain reaction (RT-PCR) of mucosal COX-2 mRNA; gastric acid secretion in pylorus-ligated animals; in vitro effects of lansoprazole (1-300 µmol/L) on the oxidation of low density lipoproteins (LDLs) induced by copper sulphate.

RESULTS: All NSAIDs elicited mucosal necrotic lesions which were associated with neutrophil infiltration and reduction of PGE2 levels. Increments of MPO and MDA contents, as well as a decrease in GSH levels were detected in the gastric mucosa of indomethacin- or piroxicam-treated animals. Indomethacin enhanced mucosal cyclooxygenase-2 expression, while not affecting cyclooxygenase-1. At the oral dose of 18 µmol/kg lansoprazole partly counteracted diclofenac-induced mucosal damage, whereas at 90 µmol/kg it markedly prevented injuries evoked by all test NSAIDs. Lansoprazole at 90 µmol/kg reversed also the effects of NSAIDs on MPO, MDA and GSH mucosal contents, without interfering with the decrease in PGE2 levels or indomethacin-induced cyclooxygenase-2 expression. However, both lansoprazole doses markedly inhibited acid secretion in pylorus-ligated rats. Lansoprazole concentration-dependently reduced the oxidation of LDLs in vitro.

CONCLUSION: These results suggest that, besides the inhibition of acid secretion, lansoprazole protection against NSAID-induced gastric damage depends on a reduction in mucosal oxidative injury, which is also responsible for an increment of sulfhydryl radical bioavailability. It is also suggested that lansoprazole does not influence the down-regulation of gastric prostaglandin production associated with NSAID treatment.

Keywords: Lansoprazole, Gastric injury, Non-steroidal anti-inflammatory drugs