flavin-adenine-dinucleotide and Body-Weight

Flavin adenine dinucleotide (FAD) is engaged in several metabolic diseases. Its main role is being a cofactor essential for the activity of many flavoproteins, which play a crucial role in electron transport pathways in living systems. The aim of this study was to apply a pegylated flavins formulation named FAD-PEG diacide complex as theranostic pathway in cancer therapy. For this purpose, a mouse liver cancer model induced by Hepa1-6 cells was used to evaluate the therapeutic efficacy of FAD (named NP1) and FAD-PEG diacide complex (named NP2). The cytokines were applied to screen the serum inflammatory factors, to establish the blood cell content of different groups of nude mice. The highlights follows that FAD formulations (NP1; NP2) significantly suppressed the tumor growth and reduced the tumor index without effects on the body weight of mice. Furthermore, NP2 significantly reduced the serum levels of cytokines IL-6, TNF-α and IL-12 (P70). The reported results provide the proof-of-concept for the synthesis of a smart adjuvant for liver cancer therapy and support their further development in the field of nanomedicine.

Topics: Animals; Antioxidants; Body Weight; Cell Line, Tumor; Cytokines; Flavin-Adenine Dinucleotide; Liver; Liver Neoplasms; Male; Mice; Mice, Nude; Polyethylene Glycols

Diets deficient in an indispensable amino acid are known to suppress food intake in rats. Few studies were focused at understanding how amino acid-deficient diets may elicit biochemical changes at the mitochondrial level. The goal of this study was to evaluate mitochondrial function in rats fed diets with 0.00, 0.18, 0.36, and 0.88% threonine (Thr) (set at 0, 30, 60, and 140% of Thr requirement for growth). Here, it is described for the first time that Thr-deficient diets induce a specific uncoupling of mitochondria in liver, especially with NADH-linked substrates, not observed in heart (except for Thr-devoid diet). The advantage of this situation would be to provide ATP to support growth and maintenance when high-quality protein food (or wealth of high-quality food in general) is available, whereas Thr-deficient diets (or deficient-quality protein food) promote the opposite, increasing mitochondrial uncoupling in liver. The uncoupling with NADH substrates would favor the use of nutrients as energy sources with higher FADH-to-NADH ratios, such as fat, minimizing the first irreversible NADH-dependent catabolism of many amino acids, including Thr, thus enhancing the use of the limiting amino acid for protein synthesis when a low quality protein source is available.

Topics: Adenosine Triphosphate; Animal Nutritional Physiological Phenomena; Animals; Body Weight; Dietary Proteins; Disease Models, Animal; Eating; Energy Metabolism; Flavin-Adenine Dinucleotide; Liver; Male; Mitochondria, Heart; Mitochondria, Liver; Myocardium; NAD; Oxidative Phosphorylation; Protein Deficiency; Rats; Rats, Sprague-Dawley; Threonine; Time Factors

We examined the changes in the amounts of water-soluble and water-insoluble proteins of rat lenses, and in glutathione reductase activity and glutathione reductase gene expression, with advancing age. The lens total protein increased in 1-month-old rats, 3-month-old rats, and 6-month-old rats, but thereafter decreased in 12-month-old-rats. The water-soluble proteins decreased with advancing age, while the water-insoluble proteins increased. The glutathione reductase activity decreased with advancing age, but the decreased glutathione reductase activity almost recovered by addition of flavin adenine dinucleotide (FAD) in vitro. However, advancing age had no effect on the level of mRNA for glutathione reductase.

Topics: Aging; Animals; Body Weight; Crystallins; Flavin-Adenine Dinucleotide; Gene Expression; Glutathione Reductase; Lens, Crystalline; Organ Size; Rats; RNA, Messenger; Solubility; Water

To study the effects of fat feeding on fat balance and hepatic mitochondrial function in postpubertal male rats.. Rats were fed low fat, medium fat or high fat diet for 15 days.. Energy balance, body composition, resting metabolic rate (RMR), mitochondrial state 3 and state 4 oxygen consumption rates, succinic dehydrogenase (EC 1.3.99.1) and mitochondrial alpha-glycerophosphate dehydrogenase (EC 1.1.1.8) activities.. Rats fed medium fat or high fat diet, in comparison with rats fed low fat diet, showed a significantly greater metabolisable energy intake and energy expenditure. In addition, body energy and lipid gains were significantly higher in rats fed medium fat or high fat diet than in rats fed low fat diet. Mitochondrial respiration and enzymatic activities were not affected by fat feeding.. These results indicate that in postpubertal rats fed high fat diets, the increase in energy expenditure counteracts only in part the excess fat deposition. This is probably due to the impairment in regulatory responses, and enhances thermogenesis.

Topics: Adipose Tissue; Animals; Basal Metabolism; Body Composition; Body Weight; Dietary Fats; Energy Intake; Energy Metabolism; Flavin-Adenine Dinucleotide; Glycerolphosphate Dehydrogenase; Lipid Metabolism; Male; Mitochondria, Liver; NAD; Oxygen Consumption; Rats; Rats, Wistar; Succinate Dehydrogenase

Riboflavin status indices in tissues (brain, liver, heart) and blood plasma, and performance parameters were studied in male and female broiler chickens in response to a wide range of dietary supplementation of riboflavin in order to establish the requirement for riboflavin in fast growing modern broilers. The birds fed riboflavin supplemented diets were increasing their body weight at a higher rate than those fed the unsupplemented diet, but this was apparent only during the first stage of growth (days 1 to 21). Supplementation of 2 mg riboflavin per kg was sufficient to support the maximum growth rate. Feed consumption was not affected by different levels of dietary supplementation of riboflavin. The supplementation of riboflavin in the diet increased (p < 0.001) plasma riboflavin level, but the magnitude of response decreased with age. The main component in the tissues was FAD, followed by FMN and riboflavin. Overall, the dietary riboflavin supplementation had highly significant (p < 0.001) effects on tissue FAD, FMN, and riboflavin status, but the effect of supplementation was clearly pronounced only at days 7 and 14, and thereafter the status of FAD, FMN, and riboflavin in the tissues did not differ between unsupplemented and supplemented birds. Neither FAD, FMN, and riboflavin nor GSSG-RED activity correlate with the level of supplementation. Saturation levels of riboflavin in the blood plasma and tissues, corresponded with dietary riboflavin levels of supplementation at 1 to 2 mg per kg. Based on the performance and biochemical data, the dietary requirement of riboflavin for fast growing broilers should be set at a level of 5 mg/kg. The currently recommended allowance of 3.6 mg riboflavin per kg of ration is not sufficient for modern breeds of broiler chickens.

Topics: Animal Feed; Animals; Body Weight; Brain; Chickens; Dietary Supplements; Enzyme Activation; Feeding Behavior; Female; Flavin Mononucleotide; Flavin-Adenine Dinucleotide; Glutathione Reductase; Liver; Male; Myocardium; Nutritional Requirements; Riboflavin

The purpose of this study was to evaluate the oxidative capacities in hepatic mitochondria isolated from prepubertal, young adult and adult rats (40, 90 and 180 days of age, respectively). In these rats, mitochondrial respiratory rates using FAD- and NAD-linked substrates as well as mitochondrial protein mass were measured. The results show that only the oxidative capacity of FAD-linked pathways significantly declined in mitochondria from 180-day-old rats compared with those from younger animals. When we consider FAD-linked respiration expressed per g liver, no significant difference was found among rats of different ages because of an increased mitochondrial protein mass found in 180-day-old rats. However, when FAD-linked and lipid-dependent respiratory rates were expressed per 100 g body weight, significant decreases occurred in 180-day-old rats. Therefore, the decrease in liver weight expressed per 100 g body weight rather than an impaired hepatic cellular activity may be the cause of body energy deficit in 180-day-old rats.

Topics: Animals; Body Weight; Flavin-Adenine Dinucleotide; Liver; Male; Mitochondria, Liver; NAD; Organ Size; Oxidation-Reduction; Oxygen Consumption; Palmitoyl Coenzyme A; Palmitoylcarnitine; Rats; Rats, Wistar; Succinic Acid

We studied the relationship between membrane potential and respiration rate in isolated liver mitochondria from rats fed an energy dense diet. We conceptually divided the system into blocks of reactions that produced or consumed mitochondrial membrane potential and then measured the kinetic response of these blocks of reactions to this potential using NAD-linked and FAD-linked substrates. We show that decreased respiration rate with an NAD-linked substrate is accounted for by decreased kinetic response of the substrate oxidation pathway to the potential. No variation in the kinetic response of the above blocks of reactions to the potential was found using an FAD-linked substrate. These results indicate that FAD-linked and NAD-linked pathways are differently affected in rats fed an energy dense diet.

Topics: Animal Nutritional Physiological Phenomena; Animals; Body Weight; Energy Intake; Energy Metabolism; Flavin-Adenine Dinucleotide; Kinetics; Male; Membrane Potentials; Mitochondria, Liver; NAD; Oxygen Consumption; Rats; Rats, Wistar

Dehydroepiandrosterone (DHEA) treatment of rats decreases gain of body weight without affecting food intake; simultaneously, the activities of liver malic enzyme and cytosolic glycerol-3-P dehydrogenase are increased. In the present study experiments were conducted to test the possibility that DHEA enhances thermogenesis and decreases metabolic efficiency via transhydrogenation of cytosolic NADPH into mitochondrial FADH2 with a consequent loss of energy as heat. The following results provide evidence which supports the proposed hypothesis: (a) the activities of cytosolic enzymes involved in NADPH production (malic enzyme, cytosolic isocitrate dehydrogenase, and aconitase) are increased after DHEA treatment; (b) cytosolic glycerol-3-P dehydrogenase may use both NAD+ and NADP+ as coenzymes; (c) activities of both cytosolic and mitochondrial forms of glycerol-3-P dehydrogenase are increased by DHEA treatment; (d) cytosol obtained from DHEA-treated rats synthesizes more glycerol-3-P during incubation with fructose-1,6-P2 (used as source of dihydroxyacetone phosphate) and NADP+; the addition of citrate in vitro further increases this difference; (e) mitochondria prepared from DHEA-treated rats more rapidly consume glycerol-3-P added exogenously or formed endogenously in the cytosol in the presence of fructose-1,6-P2 and NADP+.

Topics: Animals; Body Temperature Regulation; Body Weight; Cells, Cultured; Citrates; Citric Acid; Cytosol; Dehydroepiandrosterone; Dihydroxyacetone Phosphate; Energy Metabolism; Flavin-Adenine Dinucleotide; Glycerolphosphate Dehydrogenase; Glycerophosphates; Glycolysis; Liver; Malate Dehydrogenase; Male; Mitochondria, Liver; Models, Biological; NADP; Oxidative Phosphorylation; Rats; Rats, Sprague-Dawley

1. Turkey poults were fed on an isolated soya protein diet supplemented with 0, 2, 4 or 8 mg riboflavin/kg between 7 and 28 d of age. Maximum body weight was attained with the 4 and 8 mg diets, and poults fed on the supplemented diet did not survive until 21 d of age. The erythrocyte glutathione reductase activation coefficient (EGRAC) of the poults was inversely related to dietary riboflavin at all ages. At 28 d of age the values for EGRAC of poults fed on the 2, 4 and 8 mg diets were 2.25, 1.59 and 1.25 respectively; at 31 d, following a single oral dose of 10 mg riboflavin administered on day 28, the same poults had EGRAC values of 1.36, 1.17 and 1.26. 2. In a second experiment, poults were fed on diets supplemented with 0, 2, 4, 8 or 12 mg riboflavin/kg. Maximum body weight was attained with the 4, 8 and 12 mg diets. At 28 d of age the EGRAC values for the 0, 2, 4, 8 and 12 mg treatments were 2.36, 2.34, 1.59, 1.28 and 1.18 respectively. The concentration of flavin in the liver was not related to riboflavin intake, whereas total flavin in the liver was positively related, being on average 94, 206, 400, 440 and 413 micrograms flavin/liver for the 0, 2, 4, 8 and 12 mg treatments respectively. 3. It is concluded that EGRAC is a sensitive indicator of riboflavin status in the turkey poult and that an EGRAC of 1.6 indicates a marginal riboflavin status. It is also concluded that liver total flavin reflects merely the effect of riboflavin on growth and liver size.

Topics: Animals; Body Weight; Erythrocytes; Flavin Mononucleotide; Flavin-Adenine Dinucleotide; Flavins; Glutathione Reductase; Liver; Nutritional Requirements; Riboflavin; Turkeys

Lactating female rats were fed diets A or B containing 18 and 12% of casein respectively, or similar diets but supplemented with 0.4% of methionine (diets AM or BM). The animals and their pups were sacrificed at the 18th day of lactation. Control non lactating female rats fed the same diets for the same period of time were also sacrificed. Total riboflavin and its various forms (flavin adenin dinucleotide, flavin mononucleotide + free riboflavin) were measured in various tissues as well as in the milk which was collected from the stomach of the pups after a time controlled suck. In the lactating females fed diets A and B as well as in the control animals fed the same diets the concentrations of riboflavin and of its various forms in plasma, liver and carcass are unchanged. However in group B, they are higher in milk and in tissues of the pups. These results seem to be due to a decrease in food intake by the lactating females fed diet B which results in a decrease in milk production which in turn induces a lower growth rate of the pups although the riboflavin consumption by the latter is unchanged. Addition of methionine to the diet B (diet BM) induces the same effects as diet A which contains the highest amount of proteins but addition of methionine to the diet A (diet AM) has no further incidence. Therefore the present study has not revealed any direct effect of methionine on riboflavin metabolism in lactating female rats and their pups since the effects are similar to an increase of the total protein level in the diet. In both cases they seem to be simply related to an increase of the food consumption.

Topics: Animals; Body Composition; Body Weight; Caseins; Dietary Proteins; Female; Flavin Mononucleotide; Flavin-Adenine Dinucleotide; Lactation; Liver; Methionine; Pregnancy; Rats; Riboflavin

1. The measurement of glutathione reductase in white cells from peripheral rat blood is described; the contribution from red cell glutathione reductase was virtually eliminated. 2. The activation of the white cell enzyme by flavin adenine dinucleotide (FAD) in vitro was measured during an eight week period of dietary riboflavin deficiency in weanling rats. 3. The activation increased progressively during the deficiency reaching about fifty per cent after eight weeks, at which time liver FAD levels had declined to 30% of the control levels and clinical symptoms of deficiency were beginning to appear. No increase in activation of white cell glutathione reductase was observed in pair-fed controls, over this time period. 4. These observations suggest that the measurement of the activation coefficient of white cell glutathione reductase could usefully supplement that of the red cell enzyme, in defining riboflavin status.

Topics: Animals; Body Weight; Enzyme Activation; Erythrocytes; Flavin-Adenine Dinucleotide; Glutathione Reductase; Leukocytes; Liver; Male; Rats; Riboflavin Deficiency

Topics: Animals; Body Weight; Cytochrome c Group; Cytochrome P-450 Enzyme System; Cytochrome Reductases; Enzyme Induction; Female; Flavin Mononucleotide; Flavin-Adenine Dinucleotide; Hydrocarbons; Liver; Methylcholanthrene; Mice; Microsomes, Liver; Mixed Function Oxygenases; Riboflavin; Riboflavin Deficiency; Time Factors

Topics: Aging; Animals; Body Weight; Brain; Dietary Fats; Female; Flavin-Adenine Dinucleotide; Fructosephosphates; Glycerol; Glycerolphosphate Dehydrogenase; Glycerophosphates; Kidney; Kidney Cortex; Kidney Medulla; Liver; Male; NAD; Phosphotransferases; Pregnancy; Rats; Spectrometry, Fluorescence

Topics: Adenosine Diphosphate; Adenosine Triphosphate; Animals; Atmosphere Exposure Chambers; Body Weight; Feeding Behavior; Flavin-Adenine Dinucleotide; Hyperbaric Oxygenation; Lung; Male; NAD; Oxidative Phosphorylation; Oxygen; Pulmonary Edema; Rats; Respiration; Succinate Dehydrogenase; Time Factors

Topics: Aniline Compounds; Animals; Body Weight; Cytochrome P-450 Enzyme System; Cytochrome Reductases; Cytochromes; Dietary Proteins; Female; Flavin Mononucleotide; Flavin-Adenine Dinucleotide; Haplorhini; Heme; Kinetics; Liver; Macaca; Methyltransferases; Microsomes, Liver; Mixed Function Oxygenases; Morphinans; Organ Size; Phospholipids; Protein Deficiency; Riboflavin

Topics: Adult; Body Weight; Clinical Enzyme Tests; Creatinine; Diet; Dietary Proteins; Erythrocytes; Flavin-Adenine Dinucleotide; Glutathione Reductase; Humans; Male; Methods; NADP; Protein Deficiency; Riboflavin; Riboflavin Deficiency; Spectrophotometry; Time Factors

Topics: Animal Nutritional Physiological Phenomena; Animals; Ascorbic Acid Deficiency; Avitaminosis; Body Weight; Erythrocytes; Flavin-Adenine Dinucleotide; Folic Acid Deficiency; Glutathione Reductase; Guinea Pigs; Humans; Liver; Pyridoxine; Rats; Riboflavin; Riboflavin Deficiency; Thiamine Deficiency; Vitamin B 6 Deficiency; Vitamin B Deficiency

Topics: Animal Nutritional Physiological Phenomena; Animals; Body Weight; Erythrocytes; Female; Flavin-Adenine Dinucleotide; Glutathione Reductase; Liver; Male; Organ Size; Rats; Riboflavin; Riboflavin Deficiency; Thiamine Deficiency; Vitamin B 6 Deficiency; Xanthine Oxidase

Topics: Aging; Animals; Body Weight; Electron Transport; Female; Flavin-Adenine Dinucleotide; Flavins; Heart; Kidney; Liver; Myocardium; NAD; Oxidoreductases; Pregnancy; Rats; Riboflavin; Succinate Dehydrogenase

Topics: Amino Acids; Analysis of Variance; Animals; Body Weight; Caseins; Depression, Chemical; Diet; Dietary Proteins; Flavin Mononucleotide; Flavin-Adenine Dinucleotide; Glutens; Glycine; Liver; Lysine; Male; Metabolism; Rats; Riboflavin; Serine; Stimulation, Chemical; Threonine; Triticum

Topics: Alcohol Oxidoreductases; Animals; Body Weight; Flavin Mononucleotide; Flavin-Adenine Dinucleotide; Glycolates; Hypothyroidism; Liver; Male; Microsomes; NADP; Organ Size; Oxidoreductases; Phosphotransferases; Rats; Riboflavin Deficiency

Topics: Animals; Body Weight; Dietary Proteins; Flavin Mononucleotide; Flavin-Adenine Dinucleotide; In Vitro Techniques; Liver; Nitrogen; Nucleosides; Organ Size; Rats; Riboflavin; Subcellular Fractions; Xanthine Oxidase