Low levels of gastric mucosal glutathione during upper gastric bleeding associated with the use of nonsteroidal anti-inflammatory drugs

Abstract

Objectives: To investigate the glutathione concentrations in gastric mucosa from patients with acute gastric bleeding related to nonsteroidal anti-inflammatory drugs (NSAIDs), and to test the influence of nutritional status on mucosal glutathione. Glutathione protects the gastrointestinal mucosa against reactive oxygen species, and glutathione content in various tissues may be depleted during malnutrition.

Methods: Endoscopic biopsies were obtained from 39 patients. Eighteen of these (9 well-nourished, 9 malnourished) presented with gastric bleeding ulcers related to NSAIDs. Twenty-one other patients (12 well-nourished, 9 malnourished) underwent normal routine diagnostic endoscopy and served as controls. Malnutrition was defined as a loss of over 10% of normal body weight and/or plasma albumin levels below 30 g/l. Gastric biopsies were taken from the fundus and antrum (controls) and from the region of the ulcer (patients with acute bleeding) and frozen quickly until glutathione analysis by high-performance liquid chromatography (HPLC) coulometric detection. Results were expressed as nmol/mg wet tissue.

Results: Gastric mucosal glutathione levels were significantly (P < 0.05) lower in both the antrum (0.81 +/- 0.34 v. 1.41 +/- 0.88 nmol/mg tissue) and the fundus (1.04 +/- 0.54 v. 1.43 +/- 0.92 nmol/mg tissue, P < 0.05) in malnourished than in well-nourished control patients. Glutathione mucosal concentrations were decreased significantly in patients with NSAID-induced gastric bleeding compared with control patients (0.38 +/- 0.36 v. 1.12 +/- 0.56 nmol/mg tissue, P < 0.001), and the lowest glutathione levels were observed in malnourished patients (0.28 +/- 0.20 v. 0.48 +/- 0.15 nmol/mg tissue in well-nourished patients, not significant).

Conclusion: Malnutrition is associated with low levels of gastric glutathione. This may contribute to the severity and the onset of haemorrhage in NSAID-induced gastric ulcers.