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HELICOBACTER PYLORI INFECTION AND GASTRIC GLUTATHIONE ELEVATION
- A Temporal Relationship To Pentose Pathway Activity In The Mouse Stomach.
R Butler, G. Matthews1, H. Huynh1, C Tran1, F. Campbell.
The 4th Western Pacific Helicobacter Congress 3rd - 6th March, 2002
ABSTRACT:
Induction of gastritis in the C57/Bl6 mouse model for H. pylori infection (SS1 strain) is delayed and subtended in severity. The mechanism of this response may mimic the initial infection in human infants. Reactive oxygen species (ROS) have been implicated in this infection and the anti-oxidant glutathione (GSH) has been shown to scavenge these free radicals preventing tissue damage. Maintenance of a highly reduced cytosol is provided primarily from the oxidative pentose phosphate pathway (OPP) in the form of NADPH. This permits recycling of oxidised glutathione (GSSG) to its reduced form and is necessary for increased synthesis of GSH. The present study aimed to investigate the levels of GSH and the activity of the rate limiting enzyme of the OPP, glucose 6-P dehydrogenase (G6PDH) in H.pylori infected mice at one, four and six months post infection. These levels were compared with a non-infected, age-matched control group.
RESULTS: After one month GSH levels were markedly elevated (2.5 fold) compared with controls (p<0.001). The levels remained high at four and six months after infection (up to three fold compared with controls) although there was a trend to diminished absolute mucosal concentrations at six months. The activity of G6PDH was 0.06 + 0.005 U/min/mg protein (mean + SEM) at one month post infection which was also significantly raised (p<0.001) above controls (0.034 + 0.002 U/min/mg protein). At both four and six months after infection these levels were further increased to levels > 0.12 + 0.01 U/min/mg protein, remaining significantly greater (p<0.001) than those seen in controls and at one month after infection. These data show that GSH levels rise soon after infection with H.pylori, peaking at four months with a slight decline at six months. G6PDH on the other hand showed a more pronounced elevation at four and six months.
CONCLUSION: These observations suggest that rises in GSH via either recycling or de novo synthesis may play a role in suppression of gastritis in this mouse model. This may have implications for initial and recurrent infection in children. Further work is required to assess the role of these elevated GSH levels in animal models and whether pre-stimulation of GSH might help prevent initial infection in both animal models and children.
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