Melanoidin, a food protein-derived advanced maillard reaction product, suppresses Helicobacter pylori in vitro and in vivo.

BACKGROUND: Extracellular urease proteins located on the surface of Helicobacter pylori are gastric mucin-targeted adhesins, which play an important role in infection and colonization to the host. In this study we have determined the inhibitory activity of a variety of melanoidins, protein-derived advanced Maillard reaction products, ubiquitously found in heat-treated foods, on urease-gastric mucin adhesion. In addition, we have determined the anticolonization effect of melanoidin I, prepared by the Maillard reaction between casein and lactose, in an animal model and in human subjects infected with this bacterium. METHODS: The inhibitory activity of each compound was determined by a competitive binding assay of labeled gastric mucin to plate-immobilized urease. Melanoidin I was used in an in vivo trial using euthymic hairless mice as an infection model. Melanoidin I was consumed for 8 weeks by subjects infected with H. pylori. The [(13)C] urease breath test and H. pylori-specific antigen in the stool (HpSA) test were performed on subjects at week 0 and week 8. RESULTS: A variety of food protein-derived melanoidins strongly inhibited urease-gastric mucin adhesion in the concentration range of 10 micro g/ml to 100 micro g/ml. In particular, melanoidin I significantly (p <.05) suppressed colonization of H. pylori in mice when given for 10 weeks via the diets. Eight weeks daily intake of 3 g melanoidin I significantly (p <.05) decreased the optical density of HpSA in subjects. CONCLUSION: Foods containing protein-derived melanoidins may be an alternative to antibiotic-based therapy to prevent H. pylori that combines safety, ease of administration and efficacy.

Involvement of toxicity as an early event in urinary bladder carcinogenesis induced by phenethyl isothiocyanate, benzyl isothiocyanate, and analogues in F344 rats.

Phenethyl isothiocyanate (PEITC)(1) and benzyl isothiocyanate (BITC), naturally occurring constituents of cruciferous vegetables, have been reported to exert inhibitory effects against development of tobacco-specific carcinogen-induced lung tumors and are regarded as promising chemopreventive agents for lung cancer. However, tumor promoting and carcinogenic activities in the rat urinary bladder have been detected in several animal models. The purpose of the present study was to investigate early changes in rat urinary bladder epithelium induced by PEITC and BITC and to explore promotion/carcinogenic mechanisms. In the first experiment, in order to assess acute toxic effects, PEITC or BITC at 0.1% each in the diet were administered to 6-week-old F344 rats for 1, 2, 3, and 7 days and sequential histopathological assessment and urinalysis were performed. In the second and third experiments, structure-activity relationships of PEITC, BITC and 8 other analogues, benzyl isocyanate and benzyl thiocyanate, and phenyl-, alpha-naphthyl-, tert-butyl-, butyl-, methyl-, and ethyl isothiocyanates (ITCs) were explored in a 14-day experiment. In the first experiment, the urinary pH was significantly lowered on day 1 by both PEITC and BITC. Striking features of toxicity, such as marked inflammatory changes characterized by cellular infiltration, apoptosis/single cell necrosis, cytoplasmic vacuolation, erosion, and hemorrhage in the urinary bladder were caused, with peaks apparent on days 2 or 3, respectively. Sequential change in 5-bromo-2'-deoxyuridine (BrdU) labeling indices was in line with the inflammatory response, but the thickness of the urinary bladder epithelium continued to gradually increase up to day 7. In the second and third experiments, simple and papillary or nodular (PN) hyperplasias were observed after 14-days treatment with PEITC, BITC, and phenyl- and butyl ITCs. These results suggest that continuous urinary epithelial cell proliferation due to cytotoxicity may play an important role in the early stage of rat urinary bladder carcinogenesis due to oral administration of ITCs. In addition, hydrophobic activity of ITCs, dependent on the alkyl carbon chain length, might strongly influence the induction of bladder lesions in rats.