Acid blockers increase the risk of prion infection in mice. - GreenMedInfo Summary
Inhibitors of gastric acid secretion increase the risk of prion infection in mice.
Scand J Gastroenterol. 2011 Sep 22. Epub 2011 Sep 22. PMID: 21936725
Department of Cancer Research and Molecular Medicine , Faculty of Medicine, Norwegian University of Science and Technology (NTNU), Trondheim , Norway.
Abstract Gastric juice is a unique combination of hydrochloric acid and the proteolytic enzyme pepsin. Its main function is to inactivate ingested microorganisms. Prions cause fatal transmissible degenerative encephalopathies in animals and man. These diseases have attracted attention due to the proposed link between bovine spongiform encephalopathy in cattle and the occurrence of a new variant Creutzfeldt-Jakob disease in humans where the most probable route of transmission is via contaminated food. The role of gastric juice in the protection against these agents is not settled. Objective. The aim of this study was to examine if drug-induced gastric hypoacidity increases the susceptibility of prion infection transmitted by the oral route. Material and methods. Forty-six mice (tg338) were given brain homogenates contaminated with scrapie by gastric intubation. Twenty-two of these animals were concomitantly dosed with omeprazole increasing the median gastric pH from 1.2 to 5.3. After 381 days, the animals were sacrificed and all the brains were examined for detection of pathogenic prion proteins by enzyme-linked immunosorbent assay and western blot. Results. Drug-induced decrease in gastric acidity more than doubled the rate (59% vs. 25%, p<0.035) of brain infection compared to controls with normal gastric acidity at the time of inoculation. Conclusions. Our results demonstrate that the normal gastric juice constitutes a significant defense against prion disease in mice. Thus, gastric hypochlorhydria would be expected to enhance the susceptibility to prion infection by the oral route. This finding may have relevance to the pathogenesis of the new variant Creutzfeldt-Jakob disease and prion diseases in general.