Corticosteroid therapy augments gastroduodenal permeability to sucrose

Objective:The aim of the present study was to investigate whether corticosteroid therapy alters gastroduodenal mucosal permeability and whether permeability alteration is associated with macroscopic mucosal damage.Methods:Eight patients taking oral corticosteroid therapy (total prednisone-equivalent dose, 1.5 ± 0.1 g; duration, ∼30 days), nine patients with multiple sclerosis taking high-dose intravenous methyl-prednisolone therapy (total dose, 11.7 ± 0.5 g; duration, ∼9 days), and 20 age- and gender-matched controls were studied. Gastroduodenal permeability was determined using sucrose as a site-specific permeability probe. Five-hour urine was collected after ingesting 100 g of sucrose and its urinary excretion rate was measured using high-pressure liquid chromatography. Gastroduodenal endoscopy was performed before steroid therapy to exclude subjects with evidence of macroscopic mucosal lesions. The sucrose test and endoscopy were repeated after completion of corticosteroid therapy.Results:The urinary sucrose excretion rates were similar in the control group and in patient groups before corticosteroid therapy. The median excretion rate of sucrose increased four (one to 28)- and eight (two to 35)-fold, respectively, as compared with pretreatment values in patients taking oral steroid and high-dose intravenous methyl-prednisolone therapy (p < 0.01). Considering all patients together, subjects who received a mean prednisone-equivalent dose of 8.4 ± 1.5 g exhibited mucosal lesions, whereas patients who received 3.3 ± 1.8 g did not (p= 0.06). The posttherapy increments in sucrose excretion rates were associated with neither the presence of macroscopic lesions nor with the total steroid dose received.Conclusion:Corticosteroid therapy augments gastroduodenal permeability and high doses are associated with macroscopic mucosal lesions. Steroid-induced permeability increase does not appear to be associated with the presence of macroscopic mucosal lesions.

[1]  M. Kasuga,et al.  Induction of cyclooxygenase 2 in gastric mucosal lesions and its inhibition by the specific antagonist delays healing in mice. , 1997, Gastroenterology.

[2]  D. Graham,et al.  Effects of aspirin and Helicobacter pylori on the gastroduodenal mucosal permeability to sucrose. , 1996, Gut.

[3]  H J Hodgson,et al.  Corticosteroids reduce regenerative repair of epithelium in experimental gastric ulcers. , 1995, Gut.

[4]  C. V. Van Itallie,et al.  Tight junctions and the molecular basis for regulation of paracellular permeability. , 1995, The American journal of physiology.

[5]  A. Macpherson,et al.  Intestinal permeability: an overview. , 1995, Gastroenterology.

[6]  J. Wallace,et al.  A simple, non-invasive marker of gastric damage: sucrose permeability , 1994, The Lancet.

[7]  S. Reingold,et al.  Megadose corticosteroids in multiple sclerosis , 1994, Neurology.

[8]  J. Alverdy,et al.  The effect of dexamethasone administration on rat intestinal permeability: the role of bacterial adherence. , 1994, Gastroenterology.

[9]  J. Wallace,et al.  Sucrose: a novel permeability marker for gastroduodenal disease. , 1993, Gastroenterology.

[10]  D. Newman,et al.  Brainstem reticular nuclei that project to the thalamus in rats: a retrograde tracer study , 1992 .

[11]  E. D. Jacobson Circulatory mechanisms of gastric mucosal damage and protection. , 1992, Gastroenterology.

[12]  H R Herschman,et al.  Dexamethasone inhibits mitogen induction of the TIS10 prostaglandin synthase/cyclooxygenase gene. , 1992, The Journal of biological chemistry.

[13]  P. Braquet,et al.  Dexamethasone‐induced gastric mucosal damage in the rat: possible role of platelet‐activating factor , 1992, British journal of pharmacology.

[14]  J. Alverdy,et al.  The Effect of Glucocorticoid Administration on Bacterial Translocation: Evidence for an Acquired Mucosal Immunodeficient State , 1991, Annals of surgery.

[15]  P. Scheltens,et al.  Quantitative MRI changes in gadolinium‐DTPA enhancement after high‐dose intravenous methylprednisolone in multiple sclerosis , 1991, Neurology.

[16]  W A Ray,et al.  Corticosteroid use and peptic ulcer disease: role of nonsteroidal anti-inflammatory drugs. , 1991, Annals of internal medicine.

[17]  E. Swabb,et al.  Double-blind, placebo-controlled endoscopic comparison of the mucosal protective effects of misoprostol versus cimetidine on tolmetin-induced mucosal injury to the stomach and duodenum. , 1988, Gastroenterology.

[18]  J. Wallace Glucocorticoid-induced gastric mucosal damage: inhibition of leukotriene, but not prostaglandin biosynthesis. , 1987, Prostaglandins.

[19]  D. K. Brown,et al.  Peptic ulcer perforation associated with steroid use. , 1987, Archives of surgery.

[20]  A. Levi,et al.  Effect of non-steroidal anti-inflammatory drugs and prostaglandins on the permeability of the human small intestine. , 1986, Gut.

[21]  T. Omae,et al.  Adrenocorticosteroid therapy and gastroduodenal lesions. , 1985, Gastrointestinal endoscopy.

[22]  H. Spiro Is the steroid ulcer a myth? , 1983, The New England journal of medicine.

[23]  T C Chalmers,et al.  Association of adrenocorticosteroid therapy and peptic-ulcer disease. , 1983, The New England journal of medicine.

[24]  H O Conn,et al.  Nonassociation of adrenocorticosteroid therapy and peptic ulcer. , 1976, The New England journal of medicine.

[25]  B. Brenner,et al.  Glomerular ultrafiltration. , 1974, Federation proceedings.

[26]  R. Menguy,et al.  Effect of cortisone on mucoprotein secretion by gastric antrum of dogs: pathogenesis of steroid ulcer. , 1963, Surgery.

[27]  W. Kanenson,et al.  The incidence of peptic ulcer among patients on long term prednisone therapy. , 1958, Gastroenterology.