Abstract
Experimental diets containing either 4.8 or 9.6% wheat bran, 8.5% beef suet, and a stock diet were fed to rats for long and short periods in order to determine their effects on hepatic drug metabolizing enzymes in comparison to a fibre-free control diet. The only dietary related changes observed were with the stock diet (41B), in the rats fed for either 12 wk or 18 months, which consistently induced 7-ethoxyresorufin-O-deethylase, a mixed-function oxidase enzyme known to be catalysed by cytochrome P448; at 12 wk this diet also induced cytochromes P450 (female rats only) and b5, and biphenyl-4-hydroxylase. At this time point 7-ethoxyresorufin-O-deethylase activity was also stimulated by both the bran diets. Intestinal drug metabolizing enzymes were found to be unaffected by three dietary levels of wheat bran (4.8, 9.6 & 28.8%), fed for 4 wk, compared to a fibre-free control diet. The effect of incorporation of safrole, an inducer of the a mixed-function oxidases and an hepatotoxic agent, into the fibre-free and 9. 6% bran diets, on the levels of intestinal mixed-function oxidases was similar in both dietary groups. This indicated that at the levels of safrole and wheat bran used , bran does not adsorb safrole in vivo or prevent its biological activity. The effect of wheat bran fed at three dietary levels, for long and short periods, on mucus synthesis was investigated, and found to be without effect. The stock diet (41B) increased mucus synthesis in the colon and duodenum, as determined by measurement of the rate of incorporation of (3H)n-acetylglucosamine into . mucus glycoproteins in mucosal homogenates. The effect of wheat bran, 8.5% beef suet and the stock diet on the sialic acid content of gastro-intestinal glycoproteins was without effect, indicating that the character of the mucus was not altered by these dietary regimes. Adverse effects of wheat bran on mineral status have been reported. A study was made using well-nourished rats, of the bone mineral stores, compared to the fibre-free diet. No adverse effects of either wheat bran (4.8 or 9.6%) or of wholemeal bread incorporated into the diet at 17 or 34%, or of the stock diet, were found in comparison to the fibre-free diet. The effect of wheat bran on the circulating levels of vitamin D, determined by radioassay, was similarly without effect. Finally, a drug-nutrient interaction, that of anti-convulsant therapy and associated folate deficiency was further investigated. Rats maintained for periods of between 13 & 18 wk on a folate deficient diet were dosed with inducing agents of the mixed-function oxidase enzyme system for periods of 4 days and 2 wk (phenobarbitone) and 7 days (3-methylcholanthrene), in order to determine whether folate deficiency prevented their inducing effects. The animals were judged to be folate deficient by determination of serum and red cell folate levels using a radioassay technique. The results conclusively showed that induction of cytochrome P450 and the mixed-function oxidase enzymes was not affected by folate deficiency, indicating that the long-term anti-convulsant treatment is probably required to elicit this adverse reaction.