METHODS OF TREATMENT AGAINST HELICOBACTER PYLORI

 METHODS OF TREATMENT AGAINST HELICOBACTER PYLORI
The Helicobacter pylori neutrophil activating protein (HPNAP) is one of the virulence factors produced by Helicobacter pylori bacteria. This protein has been shown to induce neutrophil adhesion to endothelial cells in vitro and in vivo to increase adhesion of neutrophils to endothelial cells to induce migration and activation of human neutrophils and monocytes.

HPNAP induced reactive oxygen intermediates (ROI) production induce the increase in cytosolic calcium ion concentration and the phosphorylation of cytosolic proteins, leading to the assembly of nicotinamide forming NADPH oxidase in the neutrophil plasma membrane.

Free radicals produced by neutrophils are a key element of the immune system and an effective antimicrobial agent against Helicobacter pylori as well as an agent that perpetuates mucosal damage and gastritis. Neutrophil activation results in the mediation of NADPH oxidase, the production of peroxide anions that are extremely destructive to the gastric mucosa, causes oxidative damage to the DNA and leads to significant mucosal disorder. With this unusual mechanism, Helicobacter pylori avoids oxidative killing and promotes tissue damage and ulcer. Possible inhibition of the production of reactive species may lead to an improvement in Helicobacter-induced chronic gastritis and a reduction in inflammation.

The results of this study demonstrate that the C-terminal region of HPNAP stimulates neutrophil adhesion and that arabinogalactan (AGPs) proteins from Chios mastic disrupt the HPNAP-induced neutrophil-endothelial cell adhesion process, a result that should to be further investigated and potentially exploited in the future as a possible anti-inflammatory therapy for patients with Helicobacter pylori.

Triple as well as four-fold treatment regimens have been established in the treatment of Helicobacter pylori infection. Eradication occurs after triple treatment in excess of 80% and 96% for quadryple therapy with bismuth or sodium salt. However, a significant number of mutants, especially in developing countries, have been reported to confer resistance to common antibiotics (amoxicillin, metronidazole, clarithromycin) as well as fluoroquinolones. A 35% resistance rate for clarithromycin and 26% for fluoroquinolones has been documented, a very worrying fact that greatly limits the future prospects of successful antibiotic treatment of Helicobacter pylori infection.

In addition, a high prevalence of recurrence of Helicobacter pylori infection in adults and children may occur. The incidence of annual recurrence of Helicobacter pylori is 2.67% and 13.00% in developed and developing countries respectively, according to a recent study. In view of these data, alternative methods of treatment are necessary to combat this pathogen.

HPNAP, the primary stimulant of neutrophil uptake and activation, could become an effective target of natural agents that reduce inflammation (due to their antioxidant activity) or suppress the production of inflammatory cytokines that will attract neutrophils. Also, immediate HPNAP inhibition in vivo could serve as a valuable weapon to combat Helicobacter pylori.

Reference:
  • Choli-Papadopoulou T, Kottakis F, Papadopoulos G, Pendas S. Helicobacter pylori neutrophil activating protein as target for new drugs against H. pylori inflammation. World J Gastroenterol 2011;17:2585-2591
Related product: L-Glutamine & Chios Mastiha
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