Gastric mucosal levels of prostaglandins and leukotrienes in patients with gastric ulcer after treatment with rabeprazole in comparison to treatment with ranitidine.
OBJECTIVE
Prostaglandins (PGs) and leukotrienes (LTs) are major factors involved in the defense of the gastric mucosa against ulcer formation. However, little is still known about the gastromucosa-protecting action of proton pump inhibitors (PPIs) and histamine H(2) receptor antagonists (H(2) blockers) in patients with gastric ulcer. We therefore examined the effectiveness of a PPI in protecting the gastric mucosa.


METHODS
We compared the PGE(2) and LTB(4) levels and the expression levels of cyclooxygenase (COX)-1 and COX-2 mRNA in the gastric mucosa in gastric ulcer patients between the group treated for 8 weeks with a PPI, rabeprazole (PPI group; n=5), and the group treated for 8 weeks with an H(2) blocker, ranitidine (H(2) blocker group; n=6), as well as in nonulcer subjects (control group; n=5).


RESULTS
The mucosal levels of PGE(2) and COX-2 mRNA expression were significantly lower in the ulcer patients than those in the nonulcer patients, whereas the LTB(4) level was significantly higher in the ulcer patients than that in the nonulcer patients, and it was also significantly lower in the ulcerated mucosa than that in the nonulcerated mucosa. The PPI group had a significantly increased PGE(2) and decreased LTB(4) levels in comparison to the H(2) blocker group during the ulcer-healing stage. The COX-1 mRNA expression showed no difference among the PPI and H(2) blocker groups or between before and after the treatment. However, the COX-2 mRNA expression increased in the PPI group more than that in the H(2) blocker group during the ulcer-healing stage.


CONCLUSIONS
These findings demonstrated the significant gastric-mucosa-protecting effect of PPI by increasing the PGE(2) production and reducing the LTB(4) production.
Okazaki
Michiyo
M
Department of Gastroenterology, Kochi Red Cross Hospital, Kochi, Japan.
Shimizu
Ichiro
I
Ishikawa
Momoko
M
Fujiwara
Soichiro
S
Yamamoto
Hirofumi
H
Shiraishi
Tatsuhiko
T
Horie
Takahiro
T
Iuchi
Arata
A
Ito
Susumu
S
D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000627:therapeutic use*; D015121:6-Ketoprostaglandin F1 alpha / Q000032:analysis*; D000328:Adult; D000368:Aged; D051546:Cyclooxygenase 2 / Q000235:genetics; D015232:Dinoprostone / Q000032:analysis*; D005260:Female; D005753:Gastric Mucosa / Q000737:chemistry / Q000187:drug effects*; D006801:Humans; D007975:Leukotriene B4 / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis; D064750:Rabeprazole; D011899:Ranitidine / Q000627:therapeutic use*; D013276:Stomach Ulcer / Q000188:drug therapy* / Q000378:metabolism
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D012333:RNA, Messenger; D007975:Leukotriene B4; D064750:Rabeprazole; D015121:6-Ketoprostaglandin F1 alpha; D011899:Ranitidine; D051546:Cyclooxygenase 2; D015232:Dinoprostone