Riboflavin deficiency in complicated chronic alcoholism

Rosenthal, William S.; Adham, Nabeel F.; Lopez, Rafael; Cooperman, Jack M.

doi:10.1093/ajcn/26.8.858

Cited by 42 publications

(17 citation statements)

References 6 publications

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“…Chronic alcohol consumption in humans is associated with a high prevalence of RF deficiency and suboptimal levels (4,7,9,17,22,24,27). Little is known on whether impairment in intestinal absorption and renal reabsorption processes of the vitamin contributes to the development of these abnormalities.…”

Section: Discussionmentioning

confidence: 99%

“…Molecular identity of the systems involved in these transport events have also been clarified in recent years following the cloning of three RF transport systems from mammalian tissues, i.e., riboflavin transporter-1, -2, and -3 (RFVT-1, -2, and -3; products of the SLC52A1, SLC52A2, and SLC52A3 genes, respectively) (8,41,44,45). Significant expression of RFVT-1 and -3 has been demonstrated in intestinal and renal epithelial cells, with expression of the RFVT-3 protein being exclusively localized at the apical BBM domain and that of RFVT-1 being predominantly localized at the BLM domain of these polarized epithelia (8,35,36).Studies have reported high prevalence (ranges between 15 and 50%) of RF deficiency and suboptimal levels in patients with chronic alcoholism (4,7,9,17,22,24,27). Some of these cases were associated with clear clinical signs of deficiency that are manifested in the form of cheilosis and glossitis (7,9).…”

mentioning

confidence: 99%

“…Studies have reported high prevalence (ranges between 15 and 50%) of RF deficiency and suboptimal levels in patients with chronic alcoholism (4,7,9,17,22,24,27). Some of these cases were associated with clear clinical signs of deficiency that are manifested in the form of cheilosis and glossitis (7,9).…”

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confidence: 99%

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Chronic alcohol feeding inhibits physiological and molecular parameters of intestinal and renal riboflavin transport

Subramanian

Subramanya

Ghosal

et al. 2013

American Journal of Physiology-Cell Physiology

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Vitamin B2 (riboflavin, RF) is essential for normal human health. Mammals obtain RF from exogenous sources via intestinal absorption and prevent its urinary loss by reabsorption in the kidneys. Both of these absorptive events are carrier-mediated and involve specific RF transporters (RFVTs). Chronic alcohol consumption in humans is associated with a high prevalence of RF deficiency and suboptimal levels, but little is known about the effect of chronic alcohol exposure on physiological and molecular parameters of the intestinal and renal RF transport events. We addressed these issues using rats chronically fed an alcohol liquid diet and pair-fed controls as a model. The results showed that chronic alcohol feeding significantly inhibits carrier-mediated RF transport across the intestinal brush-border and basolateral membrane domains of the polarized enterocytes. This inhibition was associated with a parallel reduction in the expression of the rat RFVT-1 and -3 at the protein, mRNA, and heterogeneous nuclear RNA (hnRNA) levels. Chronic alcohol feeding also caused a significant inhibition in RF uptake in the colon. Similarly, a significant inhibition in carrier-mediated RF transport across the renal brush-border and basolateral membrane domains was observed, which again was associated with a significant reduction in the level of expression of RFVT-1 and -3 at the protein, mRNA, and hnRNA levels. These findings demonstrate that chronic alcohol exposure impairs both intestinal absorption and renal reabsorption processes of RF and that these effects are, at least in part, mediated via transcriptional mechanism(s) involving the slc52a1 and slc52a3 genes.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Chronic alcohol feeding inhibits physiological and molecular parameters of intestinal and renal riboflavin transport

Subramanian

Subramanya

Ghosal

et al. 2013

American Journal of Physiology-Cell Physiology

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“…Numerous reports have documented a high prevalence of riboflavin (vitamin B2) deficiency in alcoholic patients (1)(2)(3)(4)(5)(6)(7)(8). In some instances, flagrant manifestations of clinically advanced deficiency are apparent in the form of glossitis and cheilosis (4,5).…”

Section: Introductionmentioning

confidence: 99%

“…In some instances, flagrant manifestations of clinically advanced deficiency are apparent in the form of glossitis and cheilosis (4,5). More commonly, evidence of deficiency is based upon biochemical laboratory tests, including decreased urinary excretion of riboflavin, low serum levels of riboflavin, and elevated activity coefficient of erythrocyte glutathione reductase, an enzyme marker for riboflavin deficiency (9-1 1).…”

Section: Introductionmentioning

confidence: 99%

Mechanisms underlying the differential effects of ethanol on the bioavailability of riboflavin and flavin adenine dinucleotide.

Pinto¹,

Huang²,

Rivlin³

1987

J. Clin. Invest.

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Chronic alcoholism is associated with a high prevalence of riboflavin deficiency. Experiments were designed in an animal model to determine whether ethanol alters selectively the absorption of riboflavin and flavin adenine dinucleotide (FAD), the predominant dietary form of the vitamin. Rats received by gavage a liver homogenate to which either I14Clriboflavin or I14C]FAD was added with either ethanol or isocaloric sucrose solutions.Ethanol markedly diminished the bioavailability of I'4CIFAD to a greater degree than that of I'4Ciriboflavin. Corroboration of an ethanol-impaired intraluminal hydrolysis of FAD was provided by using everted jejunal segments and measuring mucosal uptake of I'4Clriboflavin together with nonradiolabeled FAD. In subsequent studies with mucosal cell extracts, ethanol markedly inhibited activities of FAD pyrophosphatase and flavin mononucleotide (FMN) phosphatase. These findings suggest that dietary sources of riboflavin (FMN and FAD) are not absorbed as well in the presence of ethanol than are vitamin preparations containing riboflavin, which is utilized more readily.

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Riboflavin uptake by the human-derived liver cells Hep G2: Mechanism and regulation

et al. 1998

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The water-soluble vitamin riboflavin (RF) plays a critical role in many metabolic reactions, and thus, is essential for normal cellular functions and growth. The liver plays a central role in normal RF metabolism and is the site of maximal utilization of the vitamin. The mechanism of liver uptake of RF has been studied in animals, but no information is available describing the mechanism of the vitamin uptake in the human situation and its cellular regulation. In this study, we used the human-derived liver cells Hep G2 as an in vitro model system to address these issues. Uptake of RF by Hep G2 cells was found to be temperature- and energy-dependent but Na+-independent in nature. Uptake seemed to involve a carrier-mediated process as indicated by the saturation as a function of substrate concentration (apparent Km 0.41 +/- 0.08 microM), and by the ability of the structural analogs lumiflavin and lumichrome to inhibit the uptake process [inhibition constant (K) of 1.84 and 6.32 microM, respectively]. RF uptake was energy dependent, and was inhibited by the -SH group blocker p-chloromercuriphenylsulfonate (p-CMPS) (Ki of 0.10 mM). Specific modulators of intracellular protein kinase A (PKA)-, protein kinase C (PKC)-, and protein tyrosine kinase (PTK)-mediated pathways did not affect RF uptake by Hep G2 cells. On the other hand, specific inhibitors of Ca2+/calmodulin-mediated pathway significantly inhibited the uptake process; this effect seemed to be mediated through a decrease in the Vmax of the substrate uptake process. Maintaining Hep G2 cells in a RF-deficient growth medium was associated with a significant up-regulation in the substrate uptake; this effect was specific for RF and was mediated mainly by means of an increase in the Vmax of the uptake process. These results describe, for the first time, the mechanism and cellular regulation of RF uptake by a human-derived liver cellular preparation, and shows the involvement of a carrier-mediated system in the uptake process. Furthermore, the uptake process seems to be regulated by an intracellular Ca2+/calmodulin-mediated pathway and by extracellular substrate levels.

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Riboflavin deficiency in complicated chronic alcoholism

Cited by 42 publications

References 6 publications

Chronic alcohol feeding inhibits physiological and molecular parameters of intestinal and renal riboflavin transport

Chronic alcohol feeding inhibits physiological and molecular parameters of intestinal and renal riboflavin transport

Mechanisms underlying the differential effects of ethanol on the bioavailability of riboflavin and flavin adenine dinucleotide.

Riboflavin uptake by the human-derived liver cells Hep G2: Mechanism and regulation

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