New Approaches in Gastritis Treatment

GUILLERMO MARCIAL; CECILIA RODRÍGUEZ; MARTA MEDICI; GRACIELA FONT DE VALDEZ

Gastritis and Gastric Cancer-New Insights in Gastroprotection, Diagnosis and Treatments

InTech

Lugar: Rijeka; Año: 2011; p. 153 - 176

Gastritis is an inflammation, irritation, or erosion of the stomach lining. It can occur suddenly (acute) or gradually (chronic). When gastric mucosa is exposed to harmful agents such as aspirin, indomethacin, bile acids, toxins of Helicobacter pylori or necrotizing factors such as alcohol and corrosive agents, the mucosa develops morphological and functional changes before the injury. The development and extent of mucosa injury depends upon the agent nature. Acute injury of gastric mucosa consists on disruption of hydrophobic surface of stable layer, injury and exfoliation of surface epithelial barrier and loss of electrical function; however, when the injury get to deeper layers the gastric mucosa reacts by different ways. Microvascular endothelial damage leads to microvascular stasis, cessation of oxygen supply and nutrients transport, and finally to ischemic necrosis. Vascular changes (e.g., constriction of the veins) caused by the release of pro-inflammatory vasoactive mediators from damaged cells (mast cells, macrophages and endothelial cells) affects microcirculation and, eventually, results in mucosal necrosis. Accordingly, all these events lead to the erosions or ulceration of the gastric mucosal tissue. The difference between erosion and ulcer is that the first is confined to the mucosa, while the second one penetrates the muscularis layer producing an excessive release of vasoactive inflammatory mediators from damaged cells. These entire symptom, during or after gastritis/ulcer formation, could be avoid by using different drugs accompanied by a change in food habit. The main drugs used for gastritis treatments are: a) Antiacids: aluminum hydroxide, magnesium hydroxide, calcium carbonate, sodium bicarbonate; b) H2 blockers that reduce gastric acid secretion: cimetidine, famotidine, ranitidine, nizatidine; c) Proton-pump inhibitors that inhibit gastric acid production: omeprazole, lansoprazole, pantoprazole. Omeprazole is a prototypical proton pump inhibitor (PPI), which covalently binds and inhibits the H+/K+ ATPase necessary for acidification of the tubulovesicle of the parietal cell. This prevents acid production and raises the pH of the stomach lumen, which has been shown to be an important component of therapy for the treatment of gastritis. However, evidence suggests that omeprazole treatment may itself cause acute and chronic injury to the cells of the gastric gland, and in some cases, may produce headache, diarrhea, abdominal pain, nauseas and dizziness, skin reactions or decreased bone density resulting from prolonged treatment with this drug (Kirkpantur et al, 2009; Wilcox y Mattia, 2009) well as potential drug interactions (Ibáñez et al, 2008). Experimental studies in rabbits revealed that omeprazole leads to acute depletion of parietal cells, increasing parietal cell turnover and chronic inflammatory cells. This effect has been attributed to CCK-2 mediated pro-inflammatory effects of compensatory hypergastrinemia in response to decreased acid production (Alvarez et. al. 2007). Proton-pump-inhibitors (PPIs) are very powerful blockers of the stomach´s ability to secrete acid. PPIs are widely used in the treatment or prophylaxis of peptic ulcer and gastro-esophageal reflux disease. In addition to their well documented efficacy, these drugs are generally well tolerated and only some serious adverse effects have been reported. Neutropenia and agranulocytosis are rare adverse events associated with PPI treatments although cases of neutropenia involving omeprazole and or leukopenia related to many PPIs were reported (Moreira D., 2009). Although the drug therapy is enough to prevent or cure the illness new therapies based on usage of natural and biological products are being developed. These natural treatments include dietary supplements like beverages derived from plants (as tea) or products made with probiotic acid lactic bacteria (LAB). Although the impact of probiotic LAB strains in different gastrointestinal tract disorders are well documented, little attention has been paid to their effect on gastric disease. Probiotic foods containing probiotic LAB strains have been proposed as a natural alternative to improve the general health status, preventing various gastrointestinal disorders, such as gastric ulcers and inflammation related to H. pylori infection, gastrointestinal infections or antibiotic-associated diarrhea (Penner et. al,. 2005, Chen et. al., 2009), providing beneficial effects to the host by modulating immune functions, e.g. systemic cytokine production (Borchers et. al., 2009). Within the LAB group, Streptococcus thermophilus is widely used in dairy fermentation for elaboration of a variety of dairy products such as yogurt, fermented milks, and certain kind of cheeses (Hols et. al., 2005). The use of the term "probiotic" to S. thermophilus was always a matter of debate because of their known sensitivity to gastrointestinal conditions. However, recent studies demonstrated that some strains of this species are able to resist the adverse conditions of the gut, e.g., gastric juice and bile salts (Vinderola & Reinheimer, 2003; Guarner et. al., 2005; Rodríguez et. al., 2009, 2010) Certain LAB strains are able to produce exocellular carbohydrate polymers named exopolysaccharides (EPS). A large diversity of EPS exists regarding their chemical characteristics, molecular mass, yield, technological and functional properties (Vaningelgem et. al., 2004; Mozzi et. al., 2006). EPS plays an important role in the production of yogurt, fermented milks and soft cheeses by improving the textural, melting and sensory characteristics of the products. The health-promoting effects ascribed to probiotic strains or foods not only arise from bacteria themselves, but also from the metabolites produced during fermentation. Basically, EPS from LAB have been claimed to participate in various regulatory processes such as immunomodulatory, cholesterol-lowering, anti-ulcer activities (Ruas-Madiedo et al, 2002; Welman and Madox, 2003) and even gastritis (Nagaoka et. al., 1994) although the way of action of the biopolimers and the producing LAB strains are not yet clearly understood. Recent studies in the subject put in evidence the gastro protective effect of S. thermophilus CRL1190, its EPS, and the fermented milk prepared with the strain. The effectiveness of the fermented milk (FM-1190) was confirmed throughout in vivo assays in experimental animal models of chronic gastritis. Results obtained were encourageous since the administration of FM-1190 was effective both as preventive and as therapeutic treatment to animals with active and superficial chronic gastritis. The parameters evaluated for the gastric inflammatory activity were: gastric histology and inflammation score, number of interleukin-10 (IL-10), interferon-γ (INFγ) and tumor necrosis factor-α (TNF-α) cytokine producing cells in the gastric mucosa, and thickness of the mucus layer, one of the main parameters since it protects superficial layer tissue from the aggressive condition of stomach. Feeding the animals with the probiotic milk led to a modulation of the gastric inflammatory response, i.e., decrease in the number of cells producing pro-inflammatory cytokines such as INF- and TNF-, and increased in regulatory cytokine (IL- 10) producing cells. Similar effects on Th1 cells response were described when using different probiotic mixtures of lactobacilli, bifidobacteria and streptococci on people with inflammatory bowel disease and experimental colon cancer (de Moreno de Leblanc y Perdigón, 2004; Bibiloni et. al., 2005). The administration of FM-1190 to both gastritis models induced the synthesis of mucin and increased the gastric pH, which in turn led to an increase in the mucus layer thickness. The recovery of gastric defensive systems and layer of mucus-bicarbonate by using the FM-1190 seemed to favor the recovery of damaged gastric mucosa (Nam et. al., 2005; Lam et. al., 2007a). Scanning electronic microscopy observations confirmed the presence of greater amounts of gastric mucus in animals fed the probiotic milk and the presence of S. thermophilus CRL1190 on the gastric surface after suspension of the fermented milk animal feeding. Plants derivates had been employed by population to prevent different kind of diseases for centuries. The knowledge of plant curative properties acquired by ancient civilization that passed down from generation to generation until today is known as ?popular medicine?. This popular knowledge led science to search for the main active compounds of different plants species considered as healing, which sometimes differ from region to region (Giday et. al., 2010; Rehecho et. al., 2010; Vitalini et. al., 2010; Neves et. al., 2009; Al-Qura?n, 2009). A lot of plants around the world proved to be beneficial over gastric diseases like Artemisia absinthium in Europe (Vitalini et. al., 2009); Pelargonium roseum (geranio), Minthostachys mollis (muña) and Mentha piperita (menta) in Perú, South America (Rehecho et. al., 2010); Glechoma hereracea (malvela), Althea rosea (alteia) and Melissa officinalis (cidreira) in the northern of Portugal (Neves et. al., 2009); Brassica carinata (koza) in Ethiopia, North of Africa (Giday et. al., 2010) and Adiantum capillus-veneris (venus hair) in Jordan, Middle East (Al-Qura´n, 2009). Meanwhile, in south America, specially Argentina, there are so much plant used against gastrointestinal tract like Mentha piperita, Smallanthus spp.,Lippia turbinate and Lippia integrifolia. Solvent extracts containing mainly flavonoids or their derivates but also terpenes and di-terpenes present in the essential oil of aromatic plants seemed to be effective in gastritis (Pertino et. al.,2007; Schmeda-Hirschmann et. al., 2002).