Drug-nutrient interactions最新文献

By utilising an in vivo technique the effects of amoxicillin, cephalexin, and tetracycline-HCl on intestinal L-leucine absorption were studied in the rat. The results showed that amoxicillin caused a time-dependent and reversible inhibition of L-leucine transport while the inhibition induced by the other two antibiotics tested was not reversible. Light microscopic studies revealed that the three antibiotics were without effect on intestinal mucosal morphology.

The effects of zinc deficiency on ethanol-induced ulcers were studied. Rats fed with zinc-deficient diets for 5 weeks showed markedly lowered serum zinc levels and body weights. Ethanol 30% given orally produced gastric mucosal lesions and reduced the glutathione content in the gastric glandular mucosa in their pair-fed non-zinc-deficient controls. Zinc deficiency potentiated the glutathione-depleting and ulcer-producing effects of ethanol. N-acetylcysteine, a sulfhydryl-containing agent, protected non-zinc-deficient rats from lesions produced by 50% ethanol, whereas N-ethylmaleimide, a sulfhydryl-blocking agent, worsened ulceration. It appears that zinc deficiency intensifies ethanol-induced ulceration by permitting greater depletion of the glutathione content in the stomach.

Absorption and bioavailability of theophylline from a sustained-release gelatin capsule were investigated in 10 male rabbits after oral administration (20 mg/kg), with and without a ground capsicum fruit suspension. Comparison of pharmacokinetic parameters showed that the concomitant absorption of capsicum increases areas under plasma curves (from 86.06 +/- 9.78 mg H/liter to 138.32 +/- 17.27 mg H/liter, P less than 0.001), peak plasma levels (from 6.65 +/- 0.76 to 8.78 +/- 0.98 mg/liter, P less than 0.01), and mean residence times (from 14.94 +/- 2.97 to 20.98 +/- 5.75 H, P less than 0.001). A second administration of the capsicum suspension, 11 hours after dosing, produced a new rise of theophylline plasma levels in every rabbit. The variations in pharmacokinetic and bioavailability parameters are discussed in accordance with the mechanisms of action of capsaicin, an active compound present in capsicum fruit.

Female Swiss mice were exposed to zinc chloride (0 to 500 ug/mL) or copper sulfate (0 to 200 ug/mL) in their drinking water for 15 weeks. After 3 weeks of the exposure period, the mice were administered urethan (1.5 mg/g) intraperitoneally. Urethan-induced pulmonary adenoma formation was evaluated 12 weeks later. Zinc exposure increased the number of adenomas produced but reduced the mean tumor diameter in the intermediate treatment groups, 50 and 200 ug/mL. Exposure to copper had no effect on tumor size or on tumor number. Weight gains in the mice were not affected by copper or zinc treatment, although a dose-dependent reduction in water consumption was observed with copper. Water consumption in mice exposed to zinc was elevated in one treatment group (50 ug/mL). Urethan-induced sleeping times, which reflect the rate of urethan excretion, were prolonged by zinc exposure but were unaffected by copper exposure. This finding suggests that zinc exposure impairs the elimination of urethan and enhances its carcinogenic activity, which is manifested by increased tumor formation.

A study was undertaken to assay the various phase I and phase II drug metabolising enzymes in zinc deficiency. Male weanling Fischer rats were subjected to zinc deficiency for a period of 7 weeks. Zinc levels in the control and deficient diets were 30 mg and 1.1 mg/kg diet, respectively. At the end of the experimental period, the activities of various hepatic cytosolic and microsomal enzymes were estimated. It was observed that the activities of microsomal epoxide hydrolase (with benz(a)pyrene 4-5 oxide as substrate), uridine diphospho glucuronyl transferase (with 1-naphthol as substrate) and cytosolic glutathione-S-transferase (with chlorodinitrobenzene as substrate) were altered exclusively due to zinc deficiency. There was a change in the activities of the following enzymes, which could be due either to zinc deficiency and/or food restriction: 1) aryl hydrocarbon hydroxylase; 2) cytochrome b; 3) cytochrome c; and 4) cytochrome b5. Other enzymes studied, i.e., cytosolic epoxide hydrolases, microsomal EHSTO, and UDPGT testosterone were not different in the control and experimental groups. The results are discussed in relation to the activation of carcinogens and neoplastic formation in zinc deficiency.

Ingestion of cadmium (Cd) acetate in deionized drinking water (1 ppm) in rabbits resulted in the development of hypertension and increased left ventricular mass similar to what was observed in experimental renal hypertension (Grollman technique). Regardless of the approach, mean arterial pressures (MAP) of at least 50 mm Hg greater than those of controls developed over a 34-day period. Increased left ventricular mass relative to body weight was found in both hypertensive groups. However, only an increase in renal mass was observed in unilaterally nephrectomized animals. The increased mass of hearts and kidneys that was detected after an approximately 1-month period attests to the severity of these forms of experimental hypertension. These results demonstrate that the ingestion of drinking water contaminated with Cd can cause hypertension and an increase in left ventricular mass over a short time period in rabbits.

Elderly diabetics take more drugs than other groups of elderly patients. Their multiple drug use is largely explained by the drugs that they take for complications of their primary disease; these include cardiovascular drugs for macrovascular disease and antibiotics for secondary infections. They also take more drugs for control of other conditions that are etiologically associated with the development and progression of their diabetes, including antihypertensive agents, antilipemic agents and steroids, and nonsteroidal antiinflammatory drugs (NSAIDs), which are taken for relief of joint pain that is intensified by arthritic joints bearing excess weight. Drugs taken by elderly diabetics that contribute to the high prevalence of drug-nutrient interactions include those taken as antidiabetic agents, including both insulin and sulfonylureas as well as calcium channel blockers; they also include thiazides, loop diuretics, sulfa drugs, cephalosporin antibiotics, tetracyclines, antifungal agents, cholestyramine and colestipol, niacin, prednisone and other corticosteroids, and NSAIDs. These drugs and drug combinations contribute to the risk of hyperglycemia, which can cause nonketotic hyperglycemia in the elderly; to the risk of hypoglycemia, which in the elderly carries the risk of inducing pseudo-stroke; to the risk of drug-induced nutritional deficiencies from antilipemics and cephalosporins, which can induce vitamin K deficiency; to the risk of acute incompatibility reactions, including flush reactions from chlorpropamide, niacin, and calcium channel blockers; and to the risk of edema, anemia, and hyperkalemia from NSAIDs.(ABSTRACT TRUNCATED AT 250 WORDS)

Liver microsomes from obese and control Sprague-Dawley rats were compared for cytochrome P-450 content and the ability to metabolize various prototype substrates. Over a 40-week period, the obesity-producing energy-dense diet increased average total body mass by 50%, liver mass by 32%, and body fat mass by 292%. Spectrally detectable cytochrome P-450 per mg protein increased by 36% in hepatic microsomes from obese rats. The livers from obese rats also contained more cytochrome P-450 (87%), while microsomal protein, NADPH-cytochrome c reductase, aryl hydrocarbon hydroxylase, and UDP-glucuronosyl transferase per organ rose slightly (12-40%) but not significantly. No change in the specific activities of these enzymes occurred. Young and adult rats were transferred from pellet diet to energy-dense diet for 3 weeks to examine the influence of diet vs. obesity. This short-term dietary change increased microsomal protein per g liver as well as cytochrome P-450 per liver, per g liver, and per mg protein. Adult animals increased in body weight by 24%, making them overweight and borderline obese. However, young animals showed no increase in body or liver weight, suggesting a direct effect of the energy-dense diet on liver P-450. Dietary obesity thus increased both the relative and total amounts of liver cytochrome P-450 in rats, but not the specific activities of other enzymes. These changes in cytochrome P-450 are consistent with the increased clearance seen for several oxidized drugs in obese humans and suggest that the obese overfed rat represents a useful animal model.

In the elderly, drug treatment is used for the prevention and control of cardiovascular disease. Prevention of cardiovascular disease includes management of hypercholesterolemia to reduce risk of myocardial infarction, treatment of acute myocardial infarction to reduce the risk of recurrence, and treatment of hypertension to reduce the risk of hypertensive heart disease and stroke. Management of chronic cardiovascular disease with permanent disability is the major therapeutic goal. The most commonly treated disorders of the heart and peripheral vascular system include congestive heart failure, arrhythmias, angina, and thromboses. Reduction of plasma lipid levels may be undertaken by drug therapy as a means of preventing myocardial infarction.

Carbon tetrachloride-mediated hepatotoxicity in mice was influenced by two standard, commercially available diets and by a corn oil treatment vehicle. Animals maintained on Purina 5001 diet were less sensitive than animals maintained on Teklad LM-485 diet to hepatic intoxication by carbon tetrachloride (CCl4). Lower sensitivity of the Purina group was evidenced by significantly lower plasma alanine aminotransferase (ALT) levels and higher hepatic cytochrome P-450 levels at all dosages of CCl4. In addition to the diets, the nature of the corn oil vehicle affected toxicological responses of mice to CCl4. When the vehicle from which tocopherols had been extracted was used, CCl4 elicited about twice the levels of plasma ALT than when nonextracted corn oil was used. In conclusion, the nature of the animal diet and treatment vehicle not only can influence toxicological response, but also can be important considerations in the interpretation of toxicological data.