Effect of Feeding Nitrite, Ascorbate, Hemin, and Omeprazole on Excretion of Fecal Total Apparent N-Nitroso Compounds in Mice
| Autor: | Nilesh W. Gaikwad, Michal P. Lisowyj, Sidney S. Mirvish, Michael E. Davis |
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| Rok vydání: | 2008 |
| Předmět: |
Male
Sodium ascorbate Ascorbic Acid Toxicology Excretion Feces Mice chemistry.chemical_compound Animal science hemic and lymphatic diseases medicine Animals Drug Interactions Nitrite Sodium nitrite Omeprazole Dose-Response Relationship Drug Sodium Nitrite General Medicine Animal Feed Meat Products Dose–response relationship chemistry Biochemistry Red meat Hemin Drug Therapy Combination Nitroso Compounds medicine.drug |
| Zdroj: | Chemical Research in Toxicology. 21:2344-2351 |
| ISSN: | 1520-5010 0893-228X |
| Popis: | It was proposed that colon cancer induced by red and nitrite-preserved meat is due to meat-derived N-nitroso compounds in the colonic contents. To explore this view, we previously showed that feeding beef and hot dogs increased the fecal output of total apparent N-nitroso compounds (ANC) in mice. In the current project, adult Swiss mice were fed a semipurified diet and water containing additives for 7 days. Feces from individual mice was collected on day 7, dried, and extracted with water. Extracts were analyzed for ANC as before. Feeding 2.0 g sodium nitrite (NaNO2)/L drinking water raised fecal ANC levels from 5 to 63 nmol/g feces. In a dose-response study, fecal ANC levels were proportional to the nitrite concentration squared. Even 32 mg NaNO2/L raised fecal ANC levels 2.3-fold (P < 0.05). In other results, 64, 125, and 250 mg hemin/kg diet, fed with 2 g NaNO2/L water, showed 2.3, 2.2, and 4.6 times the ANC level for nitrite alone. Sodium nitrate (12 g/L water) did not affect fecal ANC output. Omeprazole (400 mg/kg diet) and sodium ascorbate (23 g/kg diet), when fed with 1 g NaNO2/L water, lowered fecal ANC levels by 65 and 41%, indicating that, when nitrite was fed, acid-catalyzed reactions in the stomach produced ANC, which passed down the gut to the feces. Tests indicated that nitrosothiols constituted about 20% of fecal and hot dog ANC. The observed effect of NaNO2 is thus far not consistent with the proposed hypothesis. The enhancement by hemin may help explain why red meat is a cause of colon cancer. |
| Databáze: | OpenAIRE |
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