Effect of Long-term Administration of Ammonia Water on Rat Gastric Mucosa —Combined Effect of Gastric Mucosal Protective Agents

We focused on the fact that ammonia induces gastric mucosal damage by Helicobacter pylori, and investigated the effect of ammonia water administration in two kinds of concentration of rat gastric mucosa, by allowing rats free access to ammonia water for 6 weeks. No atrophy developed in the rat gastric mucosa and mucus was maintained in the low concentration group of 0.02% ammonia water, while atrophy was observed in the antral mucosa after 4 weeks and in the body mucosa after 6 weeks of administration in the high concentration group of 0.1% ammonia water. The course of atrophy was similar to that of human atrophic gastritis due to H. pylori infection. Furthermore, both superficial and deep mucus significantly decreased. On the contrary, coadministration of geranylgeranylacetone (GGA), one of gastric mucosal protective agents, inhibited decrease in gastric mucus as well as gastric mucosal atrophy in the 0.1% ammonia water group. In that way, myeloperoxidase (MPO) activity, which is an index of tissue disorders in gastric mucosa, and lipid peroxidation (LPO) activity were significantly increased due to access to ammonia water, while GGA suppressed these activities. It was suggested that gastric mucus may act as a radical scavenger to prevent gastric mucosal damage by ammonia

Unique Enhancement of Multinuclear Giant Cell Formation in AGS Cell Line Infected with Helicobacter pylori

Helicobacter pylori (H. pylori) causes pathological changes of gastric epithelial cells induced by pathogenic factors such as CagA and VacA, namely hummingbird cells (HBC) formation and vacuolization, respectively, in cultured cell lines. Cytopathic effects of other pathogenic factors produced by H. pylori have not been reported. In this study, we examined whether H. pylori induces unique morphological changes other than HBC formation and vacuolization, and we established a new marker of the bacterial infection in vitro. The cytotoxicity of H. pylori was examined in the AGS cell line, and a new morphological change, namely multinuclear giant cells (MNGC) formation, was observed in this cell line. The enhancement of MNGC formation was observed following H. pylori infection but was not associated with CagA, which causes HBC formation. We characterized the factor causing MNGC formation enhancement as heat-stable and water-soluble, and finally considered the factor to be H. pylori lipopolysaccharide (LPS). We considered that H. pylori LPS enhances MNGC formation in vitro. The cytopathic effect may provide an important marker that may clarify the mechanism of H. pylori pathogenesis in human gastric epithelial cells

Hyperlipidemia and Fat Absorption in Model Rats with Type 2 Diabetes Mellitus

Type 2 diabetes mellitus is frequently complicated by hyperlipidemia, which is closely related to the occurrence of atherosclerotic disorders. The small intestine, which absorbs dietary lipids, plays an important role in the regulation of the serum lipid concentrations. We confirmed morphological changes in small intestinal villi in the progression of diabetes mellitus and evaluated intestinal lipid absorption by the 13C-trioctanoin breath test in model rats with type 2 diabetes mellitus (OLETF rats). We measured the height of the intestinal villous epithelium and serially measured the expiratory 13CO2 concentration after the administration of 13C-trioctanoin in OLETF rats at the ages of 28, 36, and 44 weeks. The serum total cholesterol and triglyceride concentrations were significantly higher in the OLETF rats than in the control LETO rats. The height of the small intestinal villi was increased, indicating hyperplastic change. The 13CO2 concentration was significantly increased, suggesting hyperplasia of the small intestinal villi and enhancement of lipid absorption or increased total amount absorption. Excessive lipid absorption from the small intestine was suggested to be one of the causes of hyperlipidemia (particularly hypertriglyceridemia) complicating diabetes mellitus

Fat Absorption and Morphological Changes in the Small Intestine in Model Mice with Hyperlipidemia (Apo E Deficiency)

In addition to abnormalities in lipid metabolism, the small intestine, which absorbs fat, plays an important role in the pathogenesis of hyperlipidemia. Using hyperlipidemia/arteriosclerosis models (apo E deficient mice), we measured morphological changes in the small intestinal villi, and investigated fat absorption using a 13C-trioctanoin breath test. In the apo E deficiency groups, the total cholesterol and triglyceride concentrations were higher than the values in the corresponding control groups. The height of the small intestinal villi was increased, showing a histological hyperplastic change. The concentrations of Δ13CO2 were significantly increased, suggesting the enhancement of fat absorption or an increase in the total volume of absorption. In apo E deficient mice, hyperplasia of the small intestinal villi and the enhancement of fat absorption were involved in the pathogenesis of hyperlipidemia. Excessive fat absorption in the small intestine may be one of the etiological factor for hyperlipidemia