Comparison of IY81149 with omeprazole in rat reflux oesophagitis.
1. This study was aimed at evaluating the effects of IY81149[2-[[(4methoxy-3-methyl)-2-pyridinyl]methylsulfinyl]-5-(1H-pyrrol-1-yl)-1H-benzimidazole], a new proton pump inhibitor, on the development of the surgically induced reflux oesophagitis, on gastric secretion and on lipid peroxidation which is a marker of oxidative stress. Omeprazole was used as a reference drug. We furthermore investigated the influence of quercetin and desferrioxamine (DFO) on the development of the surgically induced reflux oesophagitis in rats on gastric secretion and on lipid peroxidation. 2. IY81149 and omeprazole significantly prevented the development of reflux oesophagitis and gastric secretion in a dose-dependent manner. The ED50 values of IY81149 for inhibition of oesophagitis and volume of gastric secretion were lower than of omeprazole (5.7 vs. 14.2 micromol, 15.3 vs. 24.0 micromol, respectively). IY81149 was also more potent in the acid output inhibition with an ED50 of 6.8 micromol compared with 20.8 micromol of omeprazole. 3. Malonyldialdehyde (MDA) content, the end product of lipid peroxidation, increased significantly in the oesophageal mucosa after the induction of reflux oesophagitis. IY81149 and omeprazole significantly and dose-dependently prevented lipid peroxidation. Quercetin (200 mg kg-1, p.o.) and DFO (800 mg kg-1, i.d.) significantly prevented the development of reflux oesophagitis and inhibited the lipid peroxidation independent of their actions on gastric secretion. 4. This result suggests that IY81149 is comparable with omeprazole in the treatment of reflux oesophagitis.
Kil
B J
BJ
Department of Pharmacology, College of Pharmacy, Chung Ang University, Seoul 156-756, Republic of Korea.
Kim
I W
IW
Shin
C Y
CY
Jeong
J H
JH
Jun
C H
CH
Lee
S M
SM
Kim
D Y
DY
Huh
I H
IH
Sohn
U D
UD
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology*; D003676:Deferoxamine / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004942:Esophagitis, Peptic / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D005744:Gastric Acid / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D009853:Omeprazole / Q000494:pharmacology*; D054328:Proton Pump Inhibitors; D011794:Quercetin / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013454:Sulfoxides / Q000494:pharmacology*
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D001562:Benzimidazoles; D004791:Enzyme Inhibitors; D054328:Proton Pump Inhibitors; D013454:Sulfoxides; C119615:ilaprazole; D011794:Quercetin; D003676:Deferoxamine; D009853:Omeprazole