Effects of pectin-containing diets on the hepatic macromolecular covalent binding of 2,6-dinitro-(/sup 3/H)toluene in Fischer-344 rats
The influence of diets varying in pectin content on intestinal microfloral metabolic capacity of rats has been investigated as a possible mechanism for the alteration of toxicity of 2,6-dinitrotoluene (2,6-DNT) produced by these diets. Male F-344 rats were fed a purified diet (AIN-76A), AIN-76A plus 5% or 10% citrus pectin, or either of two cereal-based diets that vary in pectin content, NIH-07 or Purina Chow 5002. After 28 days, rats were given tritium-labeled 2,6-DNT (10 or 75 mg/kg po) and killed 12 hr later. Total hepatic macromolecular covalent binding (CVB) was determined by exhaustive extraction. The CVB of 2,6-DNT was found to be independent of diet at 10 mg/kg. However, at 75 mg/kg CVB was increased 40% by feeding 5% pectin in the purified diet and 90% by feeding 10% pectin in the purified diet. Animals fed Purina 5002 and NIH-07 had 135 and 150% higher CVB, respectively, than animals fed the purified diet alone and significantly greater CVB than animals fed the pectin supplemented diets. Elevated (two- to threefold) beta-glucuronidase and nitroreductase activities, microfloral enzymes proposed to be involved in the activation of 2,6-DNT to a toxicant, were found in the cecal contents of animals fed the pectin-containing diets which correlated with a two- to threefold increase in total number of cecal anaerobes. These results suggest that pectin-induced changes in microflora may enhance hepatoxicity after high doses of 2,6-DNT.
- Research Organization:
- Department of Biochemical Toxicology, Chemical Industry Institute of Toxicology, Research Triangle Park, North Carolina
- OSTI ID:
- 5602664
- Journal Information:
- Toxicol. Appl. Pharmacol.; (United States), Vol. 69:3
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
MICROORGANISMS
METABOLISM
NITRO COMPOUNDS
TOLUENE
DIET
GLUCURONIDASE
LARGE INTESTINE
LIVER
NITRO-GROUP DEHYDROGENASES
PECTINS
RATS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
ANIMALS
AROMATICS
BLOOD SUBSTITUTES
BODY
CARBOHYDRATES
DIGESTIVE SYSTEM
DRUGS
ENZYMES
GASTROINTESTINAL TRACT
GLANDS
GLYCOSYL HYDROLASES
HEMATOLOGIC AGENTS
HYDROCARBONS
HYDROLASES
INTESTINES
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
MAMMALS
O-GLYCOSYL HYDROLASES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
OXIDOREDUCTASES
POLYSACCHARIDES
RODENTS
SACCHARIDES
VERTEBRATES
560305* - Chemicals Metabolism & Toxicology- Vertebrates- (-1987)
550501 - Metabolism- Tracer Techniques