Effects of pectin-containing diets on the hepatic macromolecular covalent binding of 2,6-dinitro-[3H]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.
D000818:Animals; D001419:Bacteria / Q000187:drug effects; D002432:Cecum / Q000382:microbiology / Q000502:physiology; D004040:Dietary Carbohydrates / Q000494:pharmacology*; D004136:Dinitrobenzenes / Q000378:metabolism* / Q000633:toxicity; D005966:Glucuronidase / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009578:Nitrobenzenes / Q000378:metabolism*; D009601:Nitroreductases; D010088:Oxidoreductases / Q000378:metabolism; D010368:Pectins / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D014316:Tritium
D004040:Dietary Carbohydrates; D004136:Dinitrobenzenes; D009578:Nitrobenzenes; D014316:Tritium; D010368:Pectins; D010088:Oxidoreductases; D009601:Nitroreductases; D005966:Glucuronidase; C023514:2,6-dinitrotoluene