Drug-nutrient interactions最新文献

Hypercholesterolemia has been shown to cause an increased vascular reactivity to catecholamines, but the mechanisms leading to greater smooth muscle responsiveness are not clear. Since membrane lipids are associated with receptors, a change in receptor structure and affinity for agonists could have been responsible. This study examined pharmacologic characteristics of cardiac beta adrenoceptors in isolated hearts from rabbits which had been fed a high cholesterol diet for 4, 6, or 8 weeks. Parameters measured were the spontaneous rate changes of the isolated right atrium and changes in refractory period of the isolated, perfused ventricles as these were induced by cumulative doses of the beta receptor agonist isoproterenol. The efficacy of a specific beta-one adrenoceptor blocking drug, metoprolol, in blocking these effects of isoproterenol was also evaluated. The rate and refractory period responses to isoproterenol and the blocking effectiveness of metoprolol were the same in all groups, as were the maximum responses induced by the agonist. It thus appears that hypercholesterolemia does not alter membrane beta adrenoceptor responsiveness in rabbit hearts.

Young male C57BL mice were exposed nose-only to cigarette smoke 20 min/day for 8 weeks while maintained on diets containing 0, 5, and 100 ppm of vitamin E. Smoking had no effect on hepatic aryl hydrocarbon hydroxylase (AHH), UDP-glucuronyltransferase, glutathione S-transferase, parathion desulfurase, or parathion esterase activity. Lung AHH activity was increased in all smoke-exposed mice, although the increase was significantly less in animals maintained on the vitamin E-free diet. All mice on the vitamin E-free diet showed reduced lung AHH activity and increased hepatic lipid peroxidation. No other biotransformations tested were significantly altered by varying vitamin E concentrations alone or in combination with cigarette smoke. For all vitamin E diets, both the smoke-exposed and sham-treated mice gained significantly less weight than the control animals. This effect was attributed to stress induced by restraint of the animals within the smoking apparatus. The results of these experiments show that both cigarette smoke and vitamin E-deficient diets may affect xenobiotic metabolism but that the combination does not appear to alter markedly their individual effects or to induce ones not previously observed.

The combined effects of feeding rats increasing amounts of raw soy four, feeding regime (ad libitum vs one meal per day), and injection of azaserine on the incidence of pancreatic nodules were investigated over a period of 12 months. Food consumption and body weights of meal-fed rats were lower than those of their ad libitum counterparts. The difference in body weight between the ad libitum and meal-fed rats became greater as the level of raw soy flour in the diet increased. Azaserine injections did not affect food consumption or body weight. The weights of the pancreas (gm/100 gm BW) increased parallel to the level of raw soy flour in the diet. The survival rate of rats on diets containing 19% and 42% raw soy flour was greater on the meal-fed regime than in the ad libitum group, but the converse was true when the diet contained 80% raw soy flour. The number and severity of pancreatic nodules observed in azaserine-injected animals surviving at the end of 12 months increased in relation to the level of raw soy flour in the diet and was enhanced at each level by meal feeding.

Studies were undertaken to determine whether or not dietary selenium (Se), as sodium selenite, at suboptimal (unsupplemented torula yeast diets, 0.02 ppm Se) or supplemented up to dietary excess, but nontoxic, levels (5.0 ppm Se) could selectively modify hepatic and renal reduced glutathione (GSH) levels and the enzymes involved in GSH metabolism. Male rats were provided torula yeast semipurified diets containing approximately 0.02 ppm Se in the basal diet and supplements of 0.1, 2.0, or 5.0 ppm Se for 3 or 6 weeks. Hepatic GSH increased in a nonlinear manner, with increasing dietary Se at both time points. Renal GSH was not similarly influenced. Neither hepatic nor renal gamma-glutamylcysteine synthetase or gamma-glutamyl transpeptidase activities are altered by supplements of Se. This suggests that synthetic and degradation enzyme activities are not influenced by Se. The capacity for the maintenance of GSH in the reduced state by glutathione reductase activity increased with increasing levels of dietary Se in the liver but not in the kidney. In both tissues greater Se supplements yielded greater tissue burdens of Se. These results suggest that GSH metabolism in hepatic and renal systems is differentially mediated, and the basis for these differences could be influenced by the relative levels in glutathione metabolizing enzymes.