Effect of ibuprofen on cyclooxygenase and nitric oxide synthase of gastric mucosa: correlation with endoscopic lesions and adverse reactions.
The aim of this study was to evaluate the effect of ibuprofen on gastric mucosa and enzymes involved in gastroprotection in healthy volunteers. Twenty-four Helicobacter pylori-negative subjects were randomized to treatment with ibuprofen or ibuprofen-arginate (each 600 mg/6 hr during 3 days). Endoscopies were performed 1 week before and after treatment. Biopsies were taken from the gastric antrum and corpus for determination of prostaglandin E2 (PGE2) by ELISA and cyclooxygenase (COX-1 and COX-2) and nitric oxide synthase (eNOS and iNOS) by western blot. All subjects had at least one gastric lesion except for two individuals taking ibuprofen-arginate. Ibuprofen-arginate caused a lower rate of clinical adverse reactions than ibuprofen. Subjects with gastric lesions or adverse reactions had lower PGE2 levels. COX-1, COX-2, eNOS, and iNOS were detectable in all subjects. The constitutive enzymes (COX-1 and eNOS) did not change after treatment. COX-2 was higher in corpus than antrum and it increased after ibuprofen treatment. iNOS tended to increase mildly in the corpus in subjects with adverse reactions or endoscopic lesions. There were no significant differences between ibuprofen and ibuprofen-arginate in PGE2, or enzymes.
Clinical Pharmacology, Hospital Universitario de la Princesa, Madrid, Instituto Teófilo Hernando, Universidad Autónoma de Madrid, Spain.
Sonia
S
Gallego-Sandín
Jesús
J
Novalbos
Aránzazu
A
Rosado
Javier P
JP
Gisbert
María-Angeles
MA
Gálvez-Múgica
Antonio G
AG
García
José María
JM
Pajares
Francisco
F
Abad-Santos
D000293:Adolescent; D000328:Adult; D001707:Biopsy, Needle; D016001:Confidence Intervals; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects* / Q000201:enzymology* / Q000473:pathology; D005773:Gastroscopy; D006801:Humans; D007052:Ibuprofen / Q000008:administration & dosage* / Q000009:adverse effects; D007150:Immunohistochemistry; D008297:Male; D019001:Nitric Oxide Synthase / Q000187:drug effects* / Q000378:metabolism; D011336:Probability; D011446:Prospective Studies; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects* / Q000378:metabolism; D011453:Prostaglandins / Q000097:blood; D012016:Reference Values; D012307:Risk Factors; D016037:Single-Blind Method; D013931:Thromboxanes / Q000097:blood
D011453:Prostaglandins; D013931:Thromboxanes; D019001:Nitric Oxide Synthase; D011451:Prostaglandin-Endoperoxide Synthases; D007052:Ibuprofen