Biochemical Similarities Between Hypothyroidism and Riboflavin Deficiency<sup>1</sup>

Rivlin, Richard S.; Menendez, Carlos E.; Langdon, Robert

doi:10.1210/endo-83-3-461

Cited by 31 publications

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“…In the present report, chlorpromazine-treated animals had significantly increased activity coefficients of glutathione reductase even though their dietary riboflavin intake was the same as in pair-fed control rats and was -30 times the recommended dietary allowance (13). This finding certainly suggests that chlorpromazine produces an endogenous form of riboflavin deficiency, resulting from impaired formation of FAD from riboflavin, as we have previously observed in hypothyroidism (15). The present data do not exclude the possibility that chlorpromazine, which produces changes in the surface properties of membranes (28), may impede the transport of circulating riboflavin into the erythrocyte or alter the binding of FAD to erythrocyte glutathione reductase, as has been proposed for glucose-6-phosphate dehydrogenase deficiency (29).…”

Section: Discussionsupporting

confidence: 75%

Inhibition of Riboflavin Metabolism in Rat Tissues by Chlorpromazine, Imipramine, and Amitriptyline

Pinto¹,

Huang²,

Rivlin³

1981

J. Clin. Invest.

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A B S T R A C T Prompted by recognition of the similar structures of riboflavin (vitamin B2), phenothiazine drugs, and tricyclic antidepressants, our studies sought to determine effects of drugs of these two types upon the conversion of riboflavin into its active coenzyme derivative, flavin adenine dinucleotide (FAD) in rat tissues. Chlorpromazine, a phenothiazine derivative, and imipramine and amitriptyline, both tricyclic antidepressants, each inhibited the incorporation of [14C]riboflavin into [14C]FAD in liver, cerebrum, cerebellum, and heart. A variety of psychoactive drugs structurally unrelated to riboflavin were ineffective. Chlorpromazine, imipramine, and amitriptyline in vitro inhibited hepatic flavokinase, the first oftwo enzymes in the conversion ofriboflavin to FAD.Evidence was obtained that chlorpromazine administration for a 3-or 7-wk period at doses comparable on a weight basis to those used clinically has significant effects upon riboflavin metabolism in the animal as a whole: (a) the activity coefficient of erythrocyte glutathione reductase, an FAD-containing enzyme used as an index of riboflavin status physiologically, was elevated, a finding compatible with a deficiency state, (b) the urinary excretion of riboflavin was more than twice that of age-and sex-matched pair-fed control rats, and (c) after administration of chlorpromazine for a 7-wk period, tissue levels of flavin mononucleotide and FAD were significantly lower than those of pair-fed littermates, despite consumption of a diet estimated to contain 30 times the recommended dietary allowance. The present study suggests that certain psychotropic drugs interfere with riboflavin metabolism at least in part by inhibiting the conversion of riboflavin to its coenzyme derivatives, and that as a consequence of such inhibition, the overall utilization of the vitamin is impaired.Dr. Pinto is a recipient of a Future Leaders Award of The

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Section: Discussionsupporting

confidence: 75%

Inhibition of Riboflavin Metabolism in Rat Tissues by Chlorpromazine, Imipramine, and Amitriptyline

Pinto¹,

Huang²,

Rivlin³

1981

J. Clin. Invest.

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“…Estimates of the prevalence of riboflavin deficiency among alcoholics have generally varied between 15 and 50% based on the laboratory and clinical evidence examined (2,5). Deficits of riboflavin in alcoholism could lead to skin disorders (12), changes in metabolism of xenobiotic substances (13,14), abnormalities ofendocrine function (15)(16)(17)(18), disturbances in lipid metabolism (19,20), interference with energy utilization (21), and personality deterioration (22,23).…”

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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“…A similar hepatic profile as in hypothyroidism with regard to concentrations of flavin coenzymes and flavokinase activity was demonstrated in riboflavin-deficient rats (1). Consequently, a biochemical similarity between hypothyroidism and riboflavin deficiency was proposed (3).…”

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confidence: 61%

“…Administration of riboflavin to deficient KK mice returned the AC values to normal. A biochemical similarity between hypothyroidism and riboflavin deficiency has been demonstrated in that flavin coenzymes are decreased in the liver in both conditions (3). In view of this similarity, it is of interest that serum T3 levels remain normal in mice with spontaneous or induced riboflavin deficiency.…”

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confidence: 98%

Serum Triiodothyronine Concentrations in Riboflavin-Deficient, Diabetic and Normal Mice

Reddi

1978

Experimental Biology and Medicine

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Biochemical Similarities Between Hypothyroidism and Riboflavin Deficiency¹

Cited by 31 publications

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Inhibition of Riboflavin Metabolism in Rat Tissues by Chlorpromazine, Imipramine, and Amitriptyline

Inhibition of Riboflavin Metabolism in Rat Tissues by Chlorpromazine, Imipramine, and Amitriptyline

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

Serum Triiodothyronine Concentrations in Riboflavin-Deficient, Diabetic and Normal Mice

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Biochemical Similarities Between Hypothyroidism and Riboflavin Deficiency1

Cited by 31 publications

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Inhibition of Riboflavin Metabolism in Rat Tissues by Chlorpromazine, Imipramine, and Amitriptyline

Inhibition of Riboflavin Metabolism in Rat Tissues by Chlorpromazine, Imipramine, and Amitriptyline

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

Serum Triiodothyronine Concentrations in Riboflavin-Deficient, Diabetic and Normal Mice

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Biochemical Similarities Between Hypothyroidism and Riboflavin Deficiency¹