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Influence of clinical factors, drug use, and food intake on the glutathione system
  1. H Shirin1,
  2. J T Pinto2,
  3. S F Moss3
  1. 1Tel Aviv University/Edith Wolfson Medical Center, Holon, Israel
  2. 2American Health Foundation, Valhalla, NY, USA
  3. 3Brown University/Rhode Island Hospital, Providence, RI, USA
  1. Correspondence to:
    S F Moss, Rhode Island Hospital, 593 Eddy St, APC 445, Providence, RI 02903, USA;
    Steven_Moss_MD{at}Brown.edu
  1. H Hoensch4,
  2. I Morgenstern4
  1. 4Leitender Arzt, Innere Abteilung, Gastroenterologie und Onkologie, Kreiskrankenhaus Groβ-Gerau, Wilhelm Seipp-Staβe 3, 64521 Groβ-Gerau, Deutchland

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In a previous issue of Gut, Hoensch and colleagues (Gut 2002;50:23540) using antral and duodenal biopsies, reported on a variety of factors such as sex, age, drug use, and food intake that influence the concentration of glutathione and the activity of glutathione S-transferase. All of these factors either singly or in combination significantly affect glutathione metabolism within the gastric mucosa.

Curiously, one critical factor that may have influenced their measurements, namely Helicobacter pylori infection, was not mentioned in their paper. This omission is particularly important as the majority of the patients that these investigators examined had endoscopic findings strongly suggestive of infection with H pylori (gastric erythema, erosions, or ulcers). Previous studies by some of the coauthors in the Hoensch paper1,2 as well as by our group3 have clearly demonstrated that H pylori infection is associated with marked depletion by approximately 50% of reduced glutathione within the gastric epithelium, and that concentrations of reduced epithelial glutathione are restored to normal by eradication of H pylori. Failure to stratify patients for H pylori infection makes other conclusions in the study less compelling. Consideration of the presence of H pylori may explain why the antrum, the preferred site of H pylori colonisation, had the lowest concentration of reduced glutathione in the gastrointestinal tract.

H pylori is well known to induce formation of reactive oxygen species (ROS), particularly in the antrum,4 and result in oxidative damage to DNA.5 Inflammatory host cells, such as activated phagocytic leucocytes, are the primary source of this oxidative stress, although H pylori per se may generate ROS and result in stimulation of oxidative signalling pathways in gastric epithelial cells.6 Recent evidence strongly suggests that levels of reduced glutathione correlate inversely with parameters of acute and chronic inflammation in vivo.3,7 Thus attenuation of reduced glutathione in the gastric mucosa of H pylori infected patients may be due to both a direct effect of H pylori induced expression of oxidative signalling pathways and the associated inflammatory response.

Intra- and extracellular oxidative stresses induced by H pylori in association with depletion of glutathione and/or genetic polymorphisms of enzymes that control its metabolism may compromise normal epithelial cell function and enhance susceptibility to gastric cancers. In considering the gastric glutathione system, the effect of H pylori should not be ignored.

References

Authors’ reply

We appreciate very much the comments made by Shirin et al concerning our publication (Gut 2002;50:23540).

In our study (Gut 2002;50:23540), we investigated a wide variety of factors which had not been evaluated entirely at the time this paper was written. In the meantime, the reported new findings of our group on Helicobacter pylori were discovered in another patient population from the Netherlands.1,2

After we received the comments of Shirin et al, we looked again at the data of our patients from Germany to test for H pylori. We found that H pylori had a significant effect on one of the parameters of the gastrointestinal glutathione (GSH) system. The level of glutathione S- transferase (GST) A (alpha) in the antral mucosa was significantly depressed (p<0.05) in H pylori infected patients (4.8 (7.3) μg/mg cytosomal protein (n=63) v 5.6 (6.9) (n=60)). The values given are means (SD) using the Wilcoxon test for comparison of means.

The status of H pylori infectivity was determined in the gastric mucosal biopsy specimens using the urease test which was read as either positive (H pylori present) or negative (H pylori absent) from the colour reaction (CLO test).

The other parameters (GSH concentration, GST enzyme activity, levels of GST P (pi) and GST T (theta)) were not affected in the antral and duodenal mucosa by H pylori status. The GST A level of the duodenal mucosa was also not significantly influenced by H pylori.

These results corroborate the findings published recently by our research group1,2 and by Shirin and colleagues.3 In our large group of patients from Germany, H pylori infection was associated with lower GST A levels in the antral mucosa. Eradication of H pylori was performed only in patients with ulcers and erosions but these patients were not followed up by endoscopy routinely.

H pylori was the only factor that had a significant depressing effect on antral GST A level. H pylori had no influence on duodenal GST A, GST P, or antral GST T1, which confirms that vegetable and fruit stimulation of these enzymes was not confounded by H pylori.

However, it has to be considered that H pylori evaluation and eradication in patients from the Netherlands were done only in non-ulcer dyspepsia while patients from Germany comprised various pathological endoscopic diagnoses apart from non-ulcer dyspepsia.

Our cross sectional study confirms that H pylori seems to depress the GST A component of the enzymatic GSH system in the antral mucosa of the stomach. Depression of GST A levels could mean increased susceptibility of the stomach mucosa towards carcinogenic insults.

References

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