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(1997). Handbook of Nutritional Essential Mineral/Elements. Journal of the American College of Nutrition: Vol. 16, No. 5, pp. 443-443.

Addition of isoniazid (isonicotinic acid hydrazide, INH) to rat liver microsomes produced an immediate decrease in the binding of carbon monoxide to reduced cytochrome P-450. Preincubation of the microsomes with INH in the presence of NADPH produced a further decrease of carbon monoxide binding to cytochrome P-450. The latter decrease of functional cytochrome P-450 was dependent upon NADPH and oxygen and was transitory. Examination of compounds structurally related to INH indicated that both the hydrazine moiety and the aromatic ring were needed to produce both effects. Incubation of microsomes with INH also resulted in gradual increases in absorbance at 449 nm and at 493 nm which also were transitory. Thus, the decreased binding of carbon monoxide to cytochrome P-450 may have occurred concurrently with formation of these spectral intermediates. Microsomal N -demethylation and aniline p -hydroxylation were inhibited by isoniazid. Preincubation of the microsomes with INH and NADPH increased the inhibition. Thus, the decreased availability of cytochrome P-450 as observed may account for the inhibition of the mixed function oxidases by isoniazid.

A variety of foreign agents, including environmental chemicals, food additives, natural food constituents, and pharmaceuticals, enter the body every day. Many of these compounds must undergo metabolism by specific enzymes within the body to facilitate their clearance. The most important of the enzyme systems, which is found in the liver, includes the cytochrome P-450 dependent mixed function oxidase, as well as several conjugation enzymes, including sulfotransferase, glucuronyl transferase, and glutathione-S-transferase. The balance of the reactions determines the rate of metabolism and clearance of the agents, as well as the degree of intracellular damage or toxicity. Specific dietary factors, such as proteins, carbohydrates, vitamins, and minerals, affect the efficiency of these reactions.

The evolution of carbon monoxide during lipid peroxidation has been demonstrated in microsomal membranes. The formation of carbon monoxide was dependent on the peroxidation process, but independent of the initiators (NADPH-ADP·Fe +3 or Ascorbate·Fe +3 ) used. Contrary to published results, the carbon monoxide does not result from heme catabolism. Carbon monoxide was generated during the peroxidation of isolated phospholipids, indicating that carbon monoxide may form directly during the peroxidative degradation of unsaturated fatty acids.

Medications can affect, and be affected by, nutrition. The interactions between drugs and various components in the diet are in part responsible for the erratic drug responses observed in patients. Because of the diversity of food consumption patterns among individuals and the widespread use of drugs, an array of varied and complicated side effects can occur. When vitamins, minerals, or other food components alter drug utilization or when drugs induce nutritional deficiencies, the effect poses a risk to the patient. Drugs can also affect many nutrition-related factors, such as appetite, taste acuity, and gastrointestinal function. Dietary habits or metabolic changes should be examined carefully and evaluated in any patient who unexpectedly gains or loses weight while taking drugs. Medicated patients need to be aware of good nutrition practices and to understand the importance of dietary modifications associated with certain diseases. A nutritious diet not only makes an important contribution to the health of those individuals but also reduces the risk of nutrition disorders or altered drug efficacy. Nutrition counseling should be considered for medicated patients to help them make rational decisions about their food choices.

Cooked pork samples were stored at 3°C and analyzed for malonaldehyde (MA). MA increased to a maximum and remained there, typical behavior for a food but contrasting with pure lipid oxidation in which MA increases and then decreases as volatile MA is lost. The failure to lose MA in food products may be attributed to MA binding. Water extracts of cooked pork samples (representing approximately l /3 of the total MA) were fractionated on G-10 Sephadex and analyzed for MA. With increasing storage time, a definite change in elution pattern from free MA to bound MA took place; the binding was not to protein or amino acids.

The age of the population continues to increase. At the turn of the century, 4% (about 3.1 million people) were 65 years of age or older. Today the percentage has increased to 12%, or 27.4 million people, and the prediction for the 21st century may increase to 17 to 20%. It should be noted that the number of individuals 85 years of age and older, as well as those over the age of 100, is increasing rapidly. The nutritional problems of the elderly are related to physiological decline, to low economic status and limited food consumption, and to a multitude of disease processes and the therapeutic regimens prescribed to cure or treat those illnesses. Examined as a group, the elderly at first appear to be less uniform in their health status than younger members of the population. However, only 10% of the elderly population contributes to the disproportionate (30%) expenditure of health care services. A majority of the elderly are normal, healthy individuals. Yet, with each decade of life the percentage of the elderly population needing additional care increases. The national nutritional surveys (National Food Consumption Survey and the National Health and Nutrition Examination Surveys, I and II) used entirely different methodologies, but reported very similar findings. The mean intake of this population was actually quite good, revealing low intakes of calcium and iron in the elderly female population. However, the standard deviation of the intake data strongly suggests a major portion of the population is at nutritional risk. For more than 30% of the population, nutrient intakes below two thirds of the recommended dietary allowances (RDA) occurred for calories, calcium, and vitamin A, while for more than 20% of the population, iron and vitamin C were at risk. Although the data evaluating the effects of age on the nutritional requirements of the elderly are limited, careful interpretation of the existing assessment and intervention efforts can provide some basic guidelines. Generalities about calorie intake must be avoided, and emphasis must be placed on calorie needs. Enhanced activity should be encouraged. Protein intake for the majority of elderly exceeds the RDA, but with increased age a greater amount of high quality protein is needed to maintain nitrogen balance. The group at greatest risk is the poor elderly who may not be able to afford enough high quality protein. Increased consumption of complex carbohydrates serves several functions including decreased caloric density and enhanced nutrient intake. Decreasing total dietary fat decreases caloric intake and indirectly decreases dietary cholesterol.(ABSTRACT TRUNCATED AT 400 WORDS)

The oxidation of either NADH or NADPH by cumene hydroperoxide in rat liver microsomes is described. The Km′ for the hydroperoxide varied with the pyridine nucleotide utilized (NADPH, Km′ = 0.91 mM; NADH, Km′ = 3.3 mM). Carbon monoxide did not inhibit the peroxidase activity although a variety of other agents which interact with cytochrome P450 did produce inhibitory effects. Moreover, aminotriazole, which stimulated NADPH peroxidase activity, had an inhibitory action on NADPH peroxidase. These various experiments suggest that NADH- and NADPH-dependent peroxidase activity may be mediated by separate components of the microsomal electron transport chain, which may be distinct from but closely interacting with cytochrome P450.

Female guinea pigs were fed diets varied in ascorbic acid and iron concentration for 21 days. Tissue concentrations of ascorbic acid, iron (total, ferritin and hemosiderin) and copper were determined in blood, liver and spleen. High dietary ascorbic acid (10 times control) increased tissue ascorbic acid levels and produced a decrease in liver ferritin and hemosiderin, without altering liver or plasma total iron. Conversely, splenic total iron increased with no changes in ferritin and hemosiderin iron. The increased ascorbic acid did lower copper levels in blood and liver, 39% and 52%, respectively. In guinea pigs maintained on an ascorbic acid-free diet for 21 days, a decrease in hepatic ferritin and total iron was observed, as well as an increase in splenic hemosiderin and total iron. No change in plasma iron was observed nor were any of the copper pools altered. Intake of high dietary iron (10 times control) increased hepatic iron stores and produced a reciprocal decrease in hepatic copper. Even though splenic iron increased, no significant change in copper resulted. The significance of these nutrient interactions is discussed.

Total parenteral nutrition (TPN) and intravenous solutions used in the United States, England and New Zealand have been found to be inadvertently contaminated with aluminum (Al). Among the solution constituents currently identified as contaminated with Al are casein hydrolysates used as the protein/amino acid source, calcium and phosphate salts, heparin and albumin. In addition, a number of investigators have reported Al contamination of products given to young infants including a variety of intravenous fluids, infant formulas, vaccines and toxoids. Aluminum contamination is of concern because it has been associated with encephalopathy, bone disease, kidney damage and cholestatic liver disease.

Parenchymal cells were prepared from the livers of male Sprague-Dawley rats by collagenase perfusion and purified by a self-generating Percoll gradient. The method consisted of mixing 31% Percoll and 5 x 10(6) cells/ml, followed by centrifugation at 10,000 x g for 10 min. A self-generated gradient provided a rapid and efficient recovery of highly viable parenchymal cells. The parenchymal cells were determined to be very stable during incubation at 37 degrees C for at least 2 h. Cell integrity was evaluated by trypan blue dye exclusion, lactate dehydrogenase leakage, and membrane peroxidation. In addition, drug metabolism and conjugation were evaluated as markers of intracellular integrity. With increasing p-nitroanisole (pNA) concentration, the formation of p-nitrophenol (pNP) increased. The rate of sulfation was maximal at a pNA concentration of 0.25 mM and decreased greatly above 1.0 mM. Glucuronidation increased from 0.25 mM to a maximum rate of 2.0 mM pNA. Above 1.0 mM pNA, nonconjugated pNP increased proportionately to the decrease in sulfation. These results indicate that the cell integrity was maintained, and that these cells can be used as a model for studying drug metabolism.

Ascorbic acid deprivation for 21 days in female guinea pigs was associated with an increase in splenic hemosiderin and total iron, but no change in splenic ferritin iron. Decreases in hepatic ferritin, hemosiderin, and total iron were also produced. Upon refeeding ascorbic acid for only 3 days, elevated splenic total iron returned to control levels while the diminished hepatic iron stores remained low.

A number of agents were tested for their ability to enhance the p-hydroxylation of aniline using isolated hepatocytes as a model system. Although the observed stimulation or inhibition was not concentration dependent, various substrates for the hepatic mixed-function oxygenase (MFO) system (p-nitroanisole, 7-ethoxycoumarin, biphenyl, N,N′-dimethylaminoazobenzene, and benzphetamine) stimulated the hydroxylation at a concentration of 0.5 m m . This effect was not seen with all substrates. In general, aniline hydroxylation was not affected by the other agents tested (steroids, metabolic inhibitors and MFO inhibitors). However, enhancement was noticed with testosterone and progesterone at the lowest concentration (0.05 m m ), with 2,6-dichloro-4-nitrophenol and salicylamide at 0.05 m m and 0.5 m m and with 7,8-benzoflavone at 5.0 m m .

Spectrophotometric changes in the extent of NADPH, but not NADH, reduction of microsomal cytochrome b 5 are correlated with the utilization of oxygen and the accumulation of lipid peroxidation products. The results suggest that NADPH-cytochrome b 5 reductase (NADPH-cytochrome c reductase) participates in the reduction of obligatory ferric chelates to their ferrous form prior to the initiation of lipid peroxidation. Further, an increased oxidation of cytochrome b 5 observed only in the presence of peroxidation products implicates a peroxidase activity associated with b 5 in the microsomal electron transport chain.