| Abstract: |
The pathogenesis of peptic ulcer disease (PUD) is multifactorial including; Helicobacter pylori infection, gastric acidity, pepsin, gastrin, gastroduodenal motility, smoking of nicotine and a possible role of gastric vasopeptides.H.pylori is considered as the major pathogen in the pathogenesis of PUD, but the mechanism of its action has not been fully explained.Previous studies have shown that H.pylori infection leads to an increased production of reactive oxygen species within the gastric mucosa which are thought to play a major role in the mediation of associated disease. Recent studies have shown differences in the availability of an important antioxidant, glutathione, during chronic H.pylori infection.The aim of this work was to study the interplay between Helicobacter pylori infection, Malondialdhyde as an end product of gastric mucosal lipid per-oxidation and reduced glutathione as a window to look through for the reactive oxygen species activity. Also, we aimed to study the serum levels of vitamin A, vitamin E and selenium and their possible protective role against gastro-duodenal H.pylori-associated diseases.This study had been carried out in Hepato-Gastro-Enterology and Endoscopy Unit, Internal Medicine Department, in co-operation with Medical Biochemistry Department, Faculty of Medicine, Zagazig University during the period from December, 2004 to March, 2006.This study included 70 individuals who were divided into two major groups:A) Control Group: this included 10 apparently healthy individuals.B) Study Group: this included the following subdivisions:Group I: included 30 patients who were H.pylori positive.Group II: included 30 patients who were H.pylori negative.Each group was further subdivided into three groups according to the pathology found into:Group (a): 10 patients with gastritis.Group (b): 10 patients with gastric ulcer.Group(c): 10 patients with gastric cancer (adenocarcinoma).All participants were subjected to the following:- Thorough history taking and full clinical examination.- Routine investigations to exclude any abnormal figures including; Urine and stool analysis, L.F.T, K.F.T, C.B.C, R.B.S, chest x-ray and pelvi-abdominal ultrasound.- Upper GI endoscopy and biopsy for:*Detection of type of gastric pathology.* Detection of H.pylori infection using:1) Urease test.2) Histological examination of biopsy with special stain (modified Giemsa stain).* Malondialdhyde (MDA) level by spectrophotometry.* Reduced glutathione (GSH) level by spectrophotometry.-Serum levels of:# MDA: by spectrophotometry.# Vitamin A: by HPLC.# Vitamin E: by HPLC.# Selenium: by atomic absorption-Whole blood level of GSH by spectrophotometry.In this study, the level of serum MDA was higher in H.pylori +ve groups compared to their H.pylori –ve counterparts. A significant level was only attainable for gastritis and gastric ulcer groups, a finding that might suggest an impact for H.pylori infection on the serum MDA. It is noteworthy here to mention that gastric cancer groups (H.pylori +ve and –ve) did not differ significantly. This implies to the possibility that the overall oxidative stress imposed by the cancer process surpass any relatively minor impact of H.pylori infection.In the same context, tissue MDA was measured in gastric mucosal biopsies where a progressive increase in the level of tissue MDA was noticed starting from controls through gastritis, gastric ulcer, and lastly gastric cancer groups. A positive impact for H.pylori infection was noticed in comparing in H.pylori +ve and –ve gastritis and gastric ulcer groups, an effect that was undetectable in comparing both gastric cancer groups (H.pylori +ve and –ve). Again, a finding that might reflect the possible disproportionate contribution of the cancer process compared with H.pylori infection to the overall oxidative stress in favor of the former.Interestingly, in the present work, tissue MDA was significantly higher in H.pylori +ve gastritis and gastric ulcer groups versus controls and insignificantly, so when serum level was the measured variable. Considering the fact that serum MDA could be considered as a reflection of the overall body oxidative stress. H.pylori infection might be considered as a regional contributor and thus the tissue level within gastric biopsies reflects its maximal local impact which only partially contributes to the overall serum level.In this study whole blood reduced glutathione (GSH) levels were significantly low in comparing any of the studied groups with controls. H. pylori +ve groups showed a significant lower level compared with their H.pylori -ve counterparts. The latter suggests a role for H.pylori infection in the revolution of this association.In the present work the level of tissue GSH was lower in any of the studied groups compared to controls. Irrespective of H.pylori infection status, both cancer groups had had significantly lower levels of tissue GSH compared to controls with insignificant difference between both gastric cancer groups. The difference was significant, however, when H.pylori +ve. Gastritis and gastric ulcer groups were compared with their H.pylori –ve. Counter parts (the former groups showed the lower level). These findings suggest a positive role for H.pylori infection in reducing the level of tissue GSH. Such an effect had been minimized when gastric cancer was the associated pathology reflecting the greater impact of carcinogenesis on reducing the level of tissue GSH that surpasses any claimed impact for H.pylori infection.In this study serum vitamin A (retinol) was estimated by HPLC technique and a significant decrease in serum vitamin A level was noticed in comparing any of the studied groups to controls. This decrease is more profound in gastric cancer groups, and this might be either a cause or may be a result of exhausted body antioxidant defensive mechanisms against increased oxidative stress by cancer. H.pylori infection seems to have no role in this decrease in comparing H.pylori +ve groups with their H.pylori –ve counterparts.In the current study serum vitamin E (α-tocopherol) was measured by HPLC and a significant decrease in serum vitamin E level was noticed in comparing any of the studied groups to controls. This decrease was more profound in gastric cancer groups, and this might be an effect for the exhausted body antioxidant defensive mechanisms against increased oxidative stress by malignancy. H.pylori infection seems to have a role in this decrease in comparing H.pylori +ve groups with their H.pylori –ve counterpartsIn the present study serum selenium levels was measured and it was found that significantly lower levels were present only in comparing gastric cancer groups to controls , gastritis or gastric ulcer groups. H.pylori infection had no impact on these results.
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