Drug-nutrient interactions最新文献

Acetaminophen (ACAP) was fed to adult Swiss-Webster mice for 4 weeks to examine the effect of prolonged ACAP ingestion on hepatic reduced glutathione (GSH) concentrations. In the first experiment, male and female mice were pair-fed diets containing ACAP at levels of 0.0 (control), 0.3, 0.6, and 1.0% of diet on a dry weight basis with the total sulfur-amino acids provided at 0.5% of the diet. Hepatic GSH was depleted, and the percentage of dose excreted as the urinary ACAP-GSH-derived conjugate increased in a dose-dependent manner with increasing ACAP. Serum glutamic-pyruvic transaminase activity, relative liver weight, and hepatic microsomal protein content increased in the group given 1.0% ACAP, but microsomal aniline hydroxylation decreased. In the second experiment, adult male mice were fed ad libitum diets containing 0.0 or 0.6% ACAP with total L-methionine provided at 0.25, 0.5 (requirement level), or 1.0%. Hepatic GSH was markedly depleted 1 week after initiation of ACAP treatment in all groups except those receiving 1.0% methionine. This reduction persisted throughout the 4-week treatment period. After 4 weeks, liver cysteine was also reduced as a result of ACAP ingestion and methionine deficiency, whereas serum inorganic sulfate concentration was not changed. Reduction in hepatic cysteine levels was also prevented by 1.0% dietary methionine. The dose-dependent depletion of GSH, the trend toward an increase in ACAP-GSH-derived conjugate excretion, and the prevention of GSH depletion by providing dietary methionine in excess of requirement indicate that prolonged ingestion of ACAP may increase the requirement for sulfur-containing amino acids and limit the availability of methionine and cysteine for protein synthesis, methylation reactions, and drug detoxification.

We examined the effects of dietary vitamin E level on rat lung response to ozone (O3) inhalation. In one study, we fed 1-month-old Sprague-Dawley (SD) rats a test diet containing 0 or 50 IU vitamin E/kg for 2 months, and then exposed one-half of the animals from each dietary group to 0.8 ppm (1,568 micrograms/m3) O3 intermittently (8 hours daily) and the other half to room air for 7 days. After O3 exposure, we found significant increases in marker enzyme activities in rat lungs from both dietary groups relative to corresponding air-exposed controls, but the magnitude of increases was greater for the 0 IU than the 50 IU group. In another study, we fed 1-month-old SD rats a test diet containing 10, 50, or 500 IU vitamin E/kg for 2 months and then exposed one-half of the animals from each dietary group to 0.8 ppm (1,568 micrograms/m3) O3 continuously and the other half to room air for 4 days. The O3 exposure increased the metabolic activities in rat lungs from all three dietary groups relative to corresponding air-exposed controls, but the magnitude of increases was greater for the 10 IU than the 50 IU or 500 IU group, and the difference between the 50 IU and 500 IU groups was small. Because a greater increase in lung metabolism after O3 exposure is thought to be associated with a greater tissue injury, the results suggest that an absence of dietary vitamin E exacerbates lung injury from O3 inhalation, while its presence protects from injury. However, the magnitude of this protective effect does not increase proportionately with increased dietary vitamin E supplementation beyond a certain level.

The effects of commercially available calcium supplements (calcium carbonate, oyster shell, chelated calcium and magnesium, calcium phosphate dibasic) and milk on tissue levels and apparent absorption of calcium, magnesium, phosphorus, iron, zinc, and copper were evaluated with rats that had been made anemic by dietary iron depletion. Hematocrits of anemic rats fed the chelated calcium and magnesium were restored more slowly than rats fed the other calcium sources. The rats fed chelated calcium and magnesium also retained less iron in their livers than rats fed calcium phosphate dibasic, oyster shells, or calcium carbonate and retained less calcium in bone than rats fed milk, oyster shells, or calcium phosphate dibasic. Rats fed calcium phosphate dibasic had on average 40-fold higher levels of calcium in their kidneys than rats fed the other diets. The molar ratio of additional calcium and phosphorus in kidneys of these rats was 3:2.

Studies were conducted to investigate the effects of lead and niacin on tryptophan and serotonin metabolism in growing broiler chicks. A low-niacin basal diet based on soybean meal and glucose was supplemented with either 40 ppm niacin/kg feed or 2,000 ppm lead, as lead acetate trihydrate, or a combination of the two in a 2 x 2 factorial arrangement. The experimental diets were fed from 1 day to 3 weeks of age. The activities of several enzymes involved in tryptophan and serotonin metabolism were assayed in chicks fed each of the experimental diets. Lead reduced the activity of liver tryptophan pyrrolase but had no effect on the activity of hepatic picolinic carboxylase. Low dietary niacin had no effect on the activity of either of these enzymes. Brainstem tryptophan 5-hydroxylase activity was unaltered by either lead or niacin. Brain and liver monoamine oxidase activity was reduced by lead but was not affected by niacin. No interactions of lead and niacin were observed with any of the enzymes examined. Lead had no consistent effect on brain serotonin (5-HT) steady-state level, but it increased the level of the major metabolite of 5-HT, 5-hydroxyindoleacetic acid (5-HIAA). Monoamine oxidase blockade failed to reduce the elevated 5-HIAA level in lead-treated chicks. The drug probenecid produced an increase in 5-HIAA that was comparable to the increase caused by lead. The effects of probenecid and lead were additive. It is concluded that lead significantly altered the activity of several enzymes involved with tryptophan metabolism, whereas the dietary niacin levels employed were without effect. Additionally, lead caused the accumulation of 5-HIAA in the brain, which appeared to result from inhibition of the probenecid-sensitive acid transport system.

Female rats receiving a diet containing 20% menhaden oil beginning at 10 weeks of age and continuing for 13 weeks had hepatic benzo(a)pyrene [B(a)P] hydroxylase activity significantly higher than similar rats fed diets containing 20% corn oil or 20% oil of evening primrose. Compared to microsomes recovered from rats fed the corn oil diet, a significant increase in microsomal cytochrome P-450 content along with an increase in the activity of cytochrome P-450 mediated ethoxycoumarin O-dealkylase was evident in rats fed menhaden oil. Glutathione S-transferase activity of the cytosol of hepatocytes was increased twofold by the feeding of 20% menhaden oil, compared with the feeding of corn or primrose oil. Administration of 7,12-dimethylbenz(a)anthracene (DMBA) 21 days before instituting the diets enhanced B(a)P hydroxylase in all animals, with the activity greatest in those fed the menhaden oil. DMBA also caused a significant increase in ethoxycoumarin O-dealkylase in rats fed menhaden oil.

Moderate ethanol consumption, at the level of 18% of total energy as part of a liquid diet, was found to result in a significant increase of total vitamin A content in the esophageal mucosa in rats fed normal-zinc-containing or zinc-supplemented diets. There was also an increase in total vitamin A content in the lungs after ethanol consumption, but the change was significant only in the zinc-supplemented group. In the liver, retinyl palmitate plus oleate decreased after ethanol, whereas free retinol, retinyl stearate, and linoleate increased. Ethanol consumption resulted in a modest decrease in hepatic zinc content when expressed per gram of liver, but not per total liver (per 100 gram of body weight). Although chronic ethanol consumption at the level of 18% of total energy did not affect total hepatic vitamin A, there was still a significant increase of vitamin A content in esophagus and lungs.