Subject riboflavin

Chlorinated dibenzo ip-dioxins are contaminants of phenol-based pesticides and may enter the environment where they are subject to the action of sunlight. Rate measurements showed that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is more rapidly photolyzed in methanol than octachlorodi-benzo-p-dioxin. Initially TCDD yields 2,3,7-trichlorodiben-zo-p-dioxin, and subsequent reductive dechlorination is accompanied by ring fission. Pure dibenzo-p-dioxin gave polymeric material and some 2,2 -dihydroxybiphenyl on irradiation. Riboflavin-sensitized photolysis of the potential precursors of dioxins, 2,4-dichlorophenol and 2,4,5-trichloro-phenol, in water gave no detectable dioxins. The products identified were chlorinated phenoxyphenols and dihydroxy-biphenyls. In contrast, aqueous alkaline solutions of purified pentachlorophenol gave traces of octachlorodibenzo-p-dioxin on irradiation. 

Fig. 13 (Top) Influence of food on the absorption of different doses of riboflavin. (Bottom) Influence of food and divided doses on ascorbic acid absorption in three subjects. (Based on data from Refs. 39 and 77.)...

A number of dietary deficiencies may increase the risk of deleterious cyanide effects. Iodine deficiency is involved in the etiology of such thyroid disorders as goiter and cretinism. These disorders may be exacerbated by excess exposure to cyanide (Delange and Ermans 1971 Ermans et al. 1972). Protein deficiencies and vitamin B12, riboflavin and other vitamins and elemental deficiencies may subject people... 

Larson et al. (1992) studied the photosensitizing ability of 2, 3, 4, 5 -tetraacetylriboflavin to various organic compounds. An aqueous solution containing aniline was subjected to a medium-pressure mercury arc lamp (X >290 nm). The investigators reported that 2, 3, 4, 5 -tetraacetylribofiavin was superior to another photosensitizer, namely riboflavin, in degrading aniline. Direct photolysis of aniline without any photosensitizer present resulted in a half-life of 23 h. In the presence of riboflavin and 2, 3, 4, 5 -tetraacetylribofiavin, the half-lives were 1 min and 45 sec, respectively. Photoproducts identified in both reactions were azobenzene, phenazine, and azoxybenzene. 

The phenomenon was observed for the first time by Brdicka [13] in the reduction of riboflavin and methylene blue studied by d.c. polaro-graphy. It did not receive much attention until it was rediscovered by several workers studying systems such as Tl+/Tl(Hg), Pb2+/Pb(Hg), and the more obvious system Co(III)—Co(II)—tris-ethylenediamine using impedance measurements [14—16]. The confusion that arose initially in the literature around this subject in the end led to the correct theoretical description [15, 17, 18], the general treatment remaining very complex [18,19]. 

From an analytical perspective, the single most important physicochemical characteristic of riboflavin is its photosensitivity (80-82). Exposure of this vitamin to ultraviolet and visible light results in irreversible photoreduction to lumiflavin and lumichrome and loss of vitamin activity. In addition, the coenzymes are subject to hydrolysis by endogenous phosphatases that are present in a number of foods. Since these enzymes are generally inactivated by thermal processing, they are a concern only in the analysis of fresh products. 

The biosynthesis of riboflavin, from the nucleotide guanosine triphosphate (GTP), requires at least six enzymatic activities and is subject to a complex regulation architecture [136, 139]. The genes that encode the enzymes have been identified and cloned [136]. 

Tissue concentrations of flavin coenzymes in hypothyroid animals may be as low as in those fed a riboflavin-deficient diet, in hypothyroid patients, erythrocyte glutathione reductase (EGR) activity may be as low, and its activation by FAD added in vitro (Section 7.5.2) as high, as in riboflavin-deficient subjects. Tissue concentrations of flavin coenzymes and EGR are normalized by the administration of thyroid hormones, with no increase in riboflavin intake (Cimino et al., 1987). 

A number of studies have noted that, in areas where malaria is endemic, riboflavin-deficient subjects are relatively resistant and have a lower parasite burden than adequately nourished subjects. Dietary deficiency of riboflavin, hypothyroidism, which induces functional riboflavin deficiency by lowering the synthesis of flavokinase (Section 7.2.4), or the administration of chlor-promazine, which inhibits flavokinase and can cause functional riboflavin deficiency (Section 7.4.4), all inhibit the growth of malarial parasites in experimental animals. However, although parasitemia is less in riboflavin deficiency, the course of the disease may be more severe (Dutta et al., 1985 Dutta, 1991 Akompong et al., 2000a, 2000b Shankar, 2000). 

Like glutathione reductase, pyridoxine oxidase is sensitive to riboflavin depletion. In normal subjects and in experimental animals, the EGR and pyridoxine oxidase activation coefficients are correlated, and both reflect riboflavin nutritional status. In subjects with glucose 6-phosphate dehydrogenase deficiency, there is an apparent protection of EGR, so that even in riboflavin deficiency it does not lose its cofactor, and the EGR activation coefficient remains within the normal range. The mechanism of this protection is unknown. In such subjects, the erythrocyte pyridoxine oxidase activation coefficient gives a response that mirrors riboflavin nutritional status (Clements and Anderson, 1980). 

On the basis of depletion/repletion studies, the minimum adult requirement for riboflavin is 0.5 to 0.8 mg per day. In population studies, values of the EGR activation coefficient <1.3 are seen in subjects whose habitual intake of riboflavin is 1.2 to 1.5 mg per day. At intakes between 1.1 to 1.6 mg per day urinary excretion rises sharply, suggesting that tissue reserves are saturated. On the basis of such studies, reference intakes (see Table 7.6) are in the range of 1.2 to 1.6 mg per day (Bates, 1987a, 1987b). 

A study for examining the feasibility of using stable iron isotopes to measure iron absorption by human subjects was carried out as part of a 12 week study of the effects of exercise on riboflavin requirements (20). The study was carried out in the Francis Johnson-Charlotte Young Human Nutrition Unit... 

Among the water-soluble vitamins subject to photodegradation during administration, thiamine, ascorbic acid, and riboflavine must be considered. A multivitamin product containing all of these vitamins was added to both 0.9% NaCl and 5% dextrose infusion solutions packaged in PVC and Clearflex containers. These admixtures were then exposed to photonic energy (2000 lux) for 24 hours and showed a rapid degradation of both riboflavine and ascorbic acid (95). 

Urinary excretions of nicotinic acid metabolites and 2-pyridone, as well as of 4-pyridoxic and xanthurenic acids were determined in 15 South African Bantu pellagrins before and after tryptophan administration (P13). Red blood cell riboflavine levels and serum glutamic-oxalacetic transaminase levels were also measured. The authors discussed the apparent inability of the pellagra patients to convert tryptophan to nicotinic acid as indicated by their low excretion of nicotinic acid metabolites before and after tryptophan load. The possibility that the subjects were also suffering from a riboflavine deficiency was also discussed. 

Creatinine excretion is intimately related to a relatively constant part of the body, the muscle mass. When studying the excretion of any metabolite, such as urea, calcium, or riboflavin, it might be undesirable to relate the amount of urinary metabolite to bodily weight, because the body contains compartments that are of minimal importance relative to metabolism. The body of an obese person contains a large amount of tissue (adipose tissue) that is inetaboiicaUy and biochemically irrelevant to the metabolism of compounds such as urea, calcium, and riboflavin. A person w hosc body contains excess body fluids also has extra mass that may be irrelevant to the metabolism of these as W cll as other compounds A meaningful comparison of excretion data from different subjects or from one subject at different times is facilitated by relating the data to urinary creatinine. 

Riboflavin is another narrow absorption window compound that lacks adverse effects and does not affect the gastric motility. It is often used as a model drug to assess the PK aspects of newly developed CR-GRDF in animal and human subjects. 

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