Drug-nutrient interactions最新文献

The objective of this study was to determine if 15% and 30% feed restriction would enhance drug metabolism similar to that caused by 45% feed restriction. Four groups of weanling male Sprague-Dawley rats were subjected to 0%, 15%, 30%, and 45% feed restriction for 28 days. Feed restriction of 45% significantly enhanced hepatic DNA, microsomal protein, cytochrome P-450, aniline hydroxylase, p-chloromethylaniline-N-demethylase, and decreased hexobarbital sleeping time. The feed restriction of 15% and 30% did not significantly alter the above parameters of drug metabolism. The activities of NADPH-generating enzymes were enhanced by all levels of feed restriction. Thus it is concluded that 15% and 30% feed restriction did not enhance in vivo or in vitro drug metabolism to the extent enhanced by 45% restriction for the same length of time.

Radioactive 3H-butylated hydroxyanisole (BHA) at dosages of 250 or 2,500 mg/kg body weight was administered to rats either orally (po) or intraperitonealy (ip) with or without 500 mg Tween 60/kg. The pharmacokinetics of 3H-BHA were evaluated in both control and protein-deficient animals. Blood or urine and feces were collected and analyzed for 3H-BHA equivalents. Using the Autoan/Nonlin69 computer program, most pharmacokinetic profiles of BHA (250 mg/kg) were fit to one-compartment open models with first-order absorption. The exception was the model for ip administration, which resulted in a two-compartment open model with first-order absorption. Increasing the dose of BHA to 2,500 mg/kg altered pharmacokinetics of BHA; no decline in blood levels was observed 48 hours post-injection. Protein deficiency and Tween 60 in combination increased the rate of absorption of BHA. Excretion of 3H-BHA and/or its metabolites in urine and feces was complete 6.5 days after administration of 2,500 mg/kg 3H-BHA.

The effects of dietary methionine on lead and lindane toxicities in rats were studied in two experiments. Rats were fed methionine-deficient (60% of requirement) or methionine-sufficient soy protein-based diets with lead acetate added (10,000 mg/kg Pb) and treated with a single dose of lindane (25% of LD50 or 88 mg/kg, p.o.) in both experiments. In experiment I, all rats were fed ad libitum. In experiment II, rats fed the methionine-sufficient diet were pair-fed to rats fed the methionine-deficient diet. In experiments I and II, the methionine-sufficient and the methionine-deficient rats had decreased final body weights, increased liver weights, decreased hematocrits, and no changes in glutathione S-transferase activity when compared to a control group. Lead + lindane treatments increased liver glutathione levels in the methionine-sufficient and methionine-deficient rats in both experiments. However, in experiment II (pair-feeding), the methionine-sufficient rats had a much greater level of liver glutathione than the methionine-deficient rats. The methionine status of the animals seems to be an important factor in determining the liver glutathione level of pair-fed rats treated with lead + lindane.

The effects of cephalexin and tetracycline HCl on D-galactose absorption in rat small intestine were investigated. Both antibiotics inhibited D-galactose uptake into isolated intestinal mucosa in a dose-dependent fashion. In vivo studies showed that cephalexin and tetracycline HCl reduced D-galactose absorption and that the transport defect was not reversible on cessation of antibiotic perfusion. Both the active and passive components of D-glactose absorption were inhibited by the antibiotics tested. Furthermore, both drugs reduced mucosa O2 consumption and inhibited D-galactose absorption when they were perfused in a contiguous loop. We conclude that the diminished D-galactose transport by rat small intestine after tissue exposure to either cephalexin or tetracycline HCl appears to be in part due to an insufficient energy supply.

Anticonvulsant therapy is known to be associated with elevated plasma copper and ceruloplasmin levels. To investigate the effect of long-term phenytoin and/or phenobarbital administration, plasma copper, zinc, and ceruloplasmin levels were measured in two groups of patients with developmental disorders who were either living at home (study 1) or institutionalized (study 2). Plasma copper and zinc levels were measured using an atomic absorption spectrophotometric method, and ceruloplasmin levels were determined using a method measuring oxidase activity (study 1) and an immunodiffusion plate method (study 2). In both studies, the mean plasma copper and ceruloplasmin levels of the anticonvulsant groups were significantly higher than those of control groups, while the mean plasma zinc levels for the anticonvulsant and control groups were similar. Possible change in the tissue zinc/copper ratio among the patients receiving long-term anticonvulsants is discussed.

The disposition of chloramphenicol was studied in young rhesus monkeys at three levels of nutrition: control, protein-energy deficiency, and following nutritional rehabilitation. During the malnutrition phase, the plasma elimination half-life was prolonged and the plasma clearance was reduced. Simultaneously there was a decrease in the activity of chloramphenicol-specific UDP-glucuronyl transferase. These changes were reversible following nutritional rehabilitation.

Weanling rats were fed a Torula yeast-based selenium-deficient diet with or without supplementation of sodium selenite (0.2 ppm selenium) in the drinking water. After 5-6 weeks on the diet regimens, the liver glutathione peroxidase activity of the selenium-deficient groups had decreased to about 1% of the supplemented groups, and the rats were then used in experiments. Cadmium-induced effects on the drug-metabolizing system of the liver were measured as the microsomal capacity to perform N- and C-oxygenation of N, N-dimethylaniline. Cadmium in vitro caused a decrease of the cytochrome P-450-dependent C-oxygenation. This effect tended to be more prominent in the selenium-deficient groups. On the other hand, N-oxygenation was increased when cadmium was added in vitro, and no significant difference was found between selenium-deficient and -supplemented groups. However, as was found for the capacity to perform C-oxygenation, there was a tendency for lower N-oxygenation in the selenium-deficient rat. Lipid peroxidation, measured as thiobarbituric acid reactive substances in liver homogenates, was higher in selenium-deficient groups after in vivo treatment or in vitro addition of cadmium, and preincubation or phenobarbital induction enhanced this selenium-dependent difference. Although, the selenium-deficient rat seems more susceptible to cadmium-induced disturbances, 5-6 weeks of selenium deficiency was not enough to cause prominent impairment on the drug-metabolizing system as measured here and with the doses used in the present study.

Male rats from moderately selenium-deficient dams were fed a Torula yeast-based, selenium-deficient diet for 7 weeks, with or without added supplements of sodium selenite (0.2 ppm selenium) and cadmium chloride (50 ppm cadmium) in the drinking water. Cadmium caused about 10% body-weight loss in selenium-deficient, as well as in supplemented rats. Glutathione peroxidase activity in liver 105,000 g supernatant and in erythrocyte hemolysate from selenium-deficient rats was about 1% and 3%, respectively, of that in supplemented rats. A cadmium-induced decrease of glutathione peroxidase activity was found in erythrocyte and liver preparations from selenium-supplemented rats, while cadmium caused an increase of the liver activity in selenium deficiency. Selenium deficiency per se caused a significant decrease of cytochrome P-450 content, while cadmium treatment did not modify further the content of this enzyme. NADPH-cytochrome c reductase was not changed by selenium regimen or cadmium treatment, while cytochrome b5 was increased on cadmium treatment of the supplemented rat. The microsomal metabolism of N,N-dimethylaniline showed a decrease of the cytochrome P-450-dependent C-oxygenation in selenium-deficient groups. Cadmium treatment had no further significant effect. The flavin-containing monooxygenase, which performs N-oxygenation of N,N-dimethylaniline, was decreased significantly by cadmium treatment in selenium deficiency. Selenium deficiency seems thus to be connected with higher susceptibility to cadmium-induced impairments of liver detoxication functions, although progressive accumulation of cadmium in the liver appears to produce only modest effects.