Lansoprazole, a proton pump inhibitor, reduces the severity of indomethacin-induced rat enteritis.
The spread of capsule endoscopy has led to a focus on small intestinal injury induced by non-steroidal anti-inflammatory drugs (NSAIDs). However, it has been proposed that proton pump inhibitors (PPI), a strong anti-secretary agent, have anti-inflammatory action beyond acid suppression. Therefore, we evaluated the biological effects of lansoprazole, a PPI used in the clinical area, in the setting of experimental rat non-steroidal anti-inflammatory drug-induced enteritis. The animals were given indomethacin subcutaneously and the intestinal mucosa was examined 24 h later. Lansoprazole was given subcutaneously just after following indomethacin injection. Single administration of indomethacin at 10 mg/kg provoked severe hemorrhagic lesions in the small intestine, mostly the jejunum and ileum. The levels of thiobarbituric acid-reactive substances (TBARS), the myeloperoxidase (MPO) activity and the content of cytokine-induced neutrophil chemoattractant-1 (CINC-1) in the intestinal mucosa significantly increased in indomethacin-treated groups compared with the sham-operated groups. The development of intestinal lesions in response to indomethacin was dose-dependently prevented by lansoprazole at a dose of 5 mg/kg together with significant suppression of the increased level of TBARS, MPO activities and CINC-1 in the small bowel. Furthermore, the increased CINC-1 mRNA expression after administration of indomethacin was also inhibited by treatment with lansoprazole. These results suggest that lansoprazole administered exogenously prevented the small intestine against indomethacin-induced damage, the action being dependent on its anti-inflammatory and anti-oxidative responses. This evidence supports the theory that PPI have an expanding role beyond acid suppression.
Kuroda
Masaaki
M
Inflammation and Immunology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Yoshida
Norimasa
N
Ichikawa
Hiroshi
H
Takagi
Tomohisa
T
Okuda
Toshimitsu
T
Naito
Yuji
Y
Okanoue
Takeshi
T
Yoshikawa
Toshikazu
T
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000633:toxicity*; D054360:Chemokine CXCL1; D019743:Chemokines, CXC / Q000235:genetics / Q000378:metabolism; D004751:Enteritis / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D007213:Indomethacin / Q000494:pharmacology / Q000633:toxicity*; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology; D007421:Intestine, Small / Q000033:anatomy & histology / Q000378:metabolism; D064747:Lansoprazole; D008297:Male; D009853:Omeprazole / Q000031:analogs & derivatives* / Q000378:metabolism / Q000627:therapeutic use; D009195:Peroxidase / Q000378:metabolism; D054328:Proton Pump Inhibitors; D017494:Proton Pumps / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000894:Anti-Inflammatory Agents, Non-Steroidal; D054360:Chemokine CXCL1; D019743:Chemokines, CXC; C513297:Cxcl1 protein, rat; D036341:Intercellular Signaling Peptides and Proteins; D054328:Proton Pump Inhibitors; D017494:Proton Pumps; D017392:Thiobarbituric Acid Reactive Substances; D064747:Lansoprazole; D009195:Peroxidase; D009853:Omeprazole; D007213:Indomethacin