Abstract
The synthesis of gastric and duodenal mucosal prostaglandin E2, prostaglandin I2, and thromboxane B2 during a 60 minute incubation of biopsy specimens, the degree of endoscopic and histological damage, and the anti-inflammatory response were all studied after a four week, double blind study of therapeutic doses of two non-steroidal anti-inflammatory drugs, naproxen and etodolac, received by 27 patients with active rheumatoid arthritis (13 receiving naproxen, 14 etodolac). Prostaglandin values after treatment did not differ from the baseline levels when all the patients were analysed as one group. Subgroup analysis showed that naproxen suppressed gastric prostaglandin E2 from a median of 29 to 9 ng/mg protein, duodenal prostaglandin E2 from 34 to 11 ng/mg, and duodenal prostaglandin I2 from 62 to 15 ng/mg protein. No overall suppression occurred with etodolac. Also, on the second assessment patients receiving naproxen had lower gastric and duodenal prostaglandin E2 and prostaglandin I2, but higher values of duodenal thromboxane B2, than patients receiving etodolac. Both drugs had comparable anti-arthritic activity and caused microscopic gastritis in similar proportions of patients. No correlation was detected between prostaglandin values and the mucosal damage which developed in seven patients receiving naproxen (54%) and three receiving etodolac (21%). These findings indicate that, unlike naproxen, etodolac does not seem to affect gastric or duodenal prostaglandin synthesis; other mechanisms of injury need to be considered.
Full text
PDFSelected References
These references are in PubMed. This may not be the complete list of references from this article.
- Domschke S., Domschke W. Gastroduodenal damage due to drugs, alcohol and smoking. Clin Gastroenterol. 1984 May;13(2):405–436. [PubMed] [Google Scholar]
- Duggan J. M., Dobson A. J., Johnson H., Fahey P. Peptic ulcer and non-steroidal anti-inflammatory agents. Gut. 1986 Aug;27(8):929–933. doi: 10.1136/gut.27.8.929. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Grant H. W., Palmer K. R., Kelly R. W., Wilson N. H., Misiewicz J. J. Dietary linoleic acid, gastric acid, and prostaglandin secretion. Gastroenterology. 1988 Apr;94(4):955–959. doi: 10.1016/0016-5085(88)90553-7. [DOI] [PubMed] [Google Scholar]
- Hawkey C. J. Synthesis of prostaglandin E2, thromboxane B2 and prostaglandin catabolism in gastritis and gastric ulcer. Gut. 1986 Dec;27(12):1484–1492. doi: 10.1136/gut.27.12.1484. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hillier K., Smith C. L., Jewell R., Arthur M. J., Ross G. Duodenal mucosa synthesis of prostaglandins in duodenal ulcer disease. Gut. 1985 Mar;26(3):237–240. doi: 10.1136/gut.26.3.237. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kelly R. W., Deam S., Cameron M. J., Seamark R. F. Measurement by radioimmunoassay of prostaglandins as their methyl oximes. Prostaglandins Leukot Med. 1986 Sep;24(1):1–14. doi: 10.1016/0262-1746(86)90201-5. [DOI] [PubMed] [Google Scholar]
- Kelly R. W., Healy D. L., Cameron M. J., Cameron I. T., Baird D. T. The stimulation of prostaglandin production by two antiprogesterone steroids in human endometrial cells. J Clin Endocrinol Metab. 1986 Jun;62(6):1116–1123. doi: 10.1210/jcem-62-6-1116. [DOI] [PubMed] [Google Scholar]
- Konturek S. J., Obtulowicz W., Sito E., Oleksy J., Wilkon S., Kiec-Dembinska A. Distribution of prostaglandins in gastric and duodenal mucosa of healthy subjects and duodenal ulcer patients: effects of aspirin and paracetamol. Gut. 1981 Apr;22(4):283–289. doi: 10.1136/gut.22.4.283. [DOI] [PMC free article] [PubMed] [Google Scholar]
- LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
- Lanza F., Panagides J., Salom I. L. Etodolac compared with aspirin: an endoscopic study of the gastrointestinal tracts of normal volunteers. J Rheumatol. 1986 Apr;13(2):299–303. [PubMed] [Google Scholar]
- Lanza F., Rack M. F., Lynn M., Wolf J., Sanda M. An endoscopic comparison of the effects of etodolac, indomethacin, ibuprofen, naproxen, and placebo on the gastrointestinal mucosa. J Rheumatol. 1987 Apr;14(2):338–341. [PubMed] [Google Scholar]
- Lee D., Dvornik D. Etodolac: effect on prostaglandin concentrations in gastric mucosa of rats. Life Sci. 1985 Mar 25;36(12):1157–1162. doi: 10.1016/0024-3205(85)90232-2. [DOI] [PubMed] [Google Scholar]
- Ligumsky M., Golanska E. M., Hansen D. G., Kauffman G. L., Jr Aspirin can inhibit gastric mucosal cyclo-oxygenase without causing lesions in rat. Gastroenterology. 1983 Apr;84(4):756–761. [PubMed] [Google Scholar]
- Maddox I. S. The role of copper in prostaglandin synthesis. Biochim Biophys Acta. 1973 Apr 13;306(1):74–81. doi: 10.1016/0005-2760(73)90210-5. [DOI] [PubMed] [Google Scholar]
- Main I. H., Whittle B. J. Investigation of the vasodilator and antisecretory role of prostaglandins in the rat gastric mucosa by use of non-steroidal anti-inflammatory drugs. Br J Pharmacol. 1975 Feb;53(2):217–224. doi: 10.1111/j.1476-5381.1975.tb07351.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rachmilewitz D., Ligumsky M., Fich A., Goldin E., Eliakim A., Karmeli F. Role of endogenous gastric prostanoids in the pathogenesis and therapy of duodenal ulcer. Gastroenterology. 1986 Apr;90(4):963–969. doi: 10.1016/0016-5085(86)90874-7. [DOI] [PubMed] [Google Scholar]
- Redfern J. S., Lee E., Feldman M. Effect of indomethacin on gastric mucosal prostaglandins in humans. Correlation with mucosal damage. Gastroenterology. 1987 Apr;92(4):969–977. doi: 10.1016/0016-5085(87)90972-3. [DOI] [PubMed] [Google Scholar]
- Robert A. Cytoprotection by prostaglandins. Gastroenterology. 1979 Oct;77(4 Pt 1):761–767. [PubMed] [Google Scholar]
- Rosam A. C., Wallace J. L., Whittle B. J. Potent ulcerogenic actions of platelet-activating factor on the stomach. Nature. 1986 Jan 2;319(6048):54–56. doi: 10.1038/319054a0. [DOI] [PubMed] [Google Scholar]
- Stern A. I., Hogan D. L., Isenberg J. I. A new method for quantitation of ion fluxes across in vivo human gastric mucosa: effect of aspirin, acetaminophen, ethanol, and hyperosmolar solutions. Gastroenterology. 1984 Jan;86(1):60–70. [PubMed] [Google Scholar]
- Turner N. C., Martin G. P., Marriott C. The influence of native porcine gastric mucus gel on hydrogen ion diffusion: the effect of potentially ulcerogenic agents. J Pharm Pharmacol. 1985 Nov;37(11):776–780. doi: 10.1111/j.2042-7158.1985.tb04967.x. [DOI] [PubMed] [Google Scholar]
- Walt R. P., Kemp R. T., Filipowicz B., Davies J. G., Bhaskar N. K., Hawkey C. J. Gastric mucosal protection with selective inhibition of thromboxane synthesis. Gut. 1987 May;28(5):541–544. doi: 10.1136/gut.28.5.541. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Waltham-Weeks C. D. Etodolac versus naproxen in rheumatoid arthritis: a double-blind crossover study. Curr Med Res Opin. 1987;10(8):540–547. doi: 10.1185/03007998709108963. [DOI] [PubMed] [Google Scholar]
- Whitehead R., Truelove S. C., Gear M. W. The histological diagnosis of chronic gastritis in fibreoptic gastroscope biopsy specimens. J Clin Pathol. 1972 Jan;25(1):1–11. doi: 10.1136/jcp.25.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Whittle B. J., Higgs G. A., Eakins K. E., Moncada S., Vane J. R. Selective inhibition of prostaglandin production in inflammatory exudates and gastric mucosa. Nature. 1980 Mar 20;284(5753):271–273. doi: 10.1038/284271a0. [DOI] [PubMed] [Google Scholar]
- Whittle B. J., Kauffman G. L., Moncada S. Vasoconstriction with thromboxane A2 induces ulceration of the gastric mucosa. Nature. 1981 Jul 30;292(5822):472–474. doi: 10.1038/292472a0. [DOI] [PubMed] [Google Scholar]
- Whittle B. J. Temporal relationship between cyclooxygenase inhibition, as measured by prostacyclin biosynthesis, and the gastrointestinal damage induced by indomethacin in the rat. Gastroenterology. 1981 Jan;80(1):94–98. [PubMed] [Google Scholar]