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Biomedical subjects

R S Rivlin

Publications and source records attributed to R S Rivlin.

At least 37 records · Page 2Linked to original sources
PubMed1988

Enhancement of adriamycin-induced mortality during riboflavin administration and riboflavin deficiency in rats.

Adriamycin-treated rats were monitored for survivorship while consuming a normal diet adequate in riboflavin, a normal diet and receiving daily high-dose injections of riboflavin-5'-phosphate (flavin mononucleotide, FMN), or a riboflavin-deficient diet. Each animal was compared to a corresponding pair-fed, saline-treated control. In Adriamycin-treated rats fed the normal chow diet alone, survivorship declined within 7 days and remained constant after 12 days to about 50%. Adriamycin-treated rats consuming the normal diet and injected with FMN initially showed similar survivorship; however, after 20 days survival fell to 14%. Adriamycin-treated, riboflavin-deficient rats showed within 5 days a precipitous decline in survivorship which leveled to 5%. These results suggest that during Adriamycin treatment, proper riboflavin nutriture may be a crucial determinant of survival.

Animals↗
PubMed1987

Disturbances in the formation of FAD and covalently bound flavins in Novikoff hepatoma from riboflavin-deficient rats.

The incorporation of radiolabeled riboflavin into flavin mononucleotide, flavin adenine dinucleotide, and flavin covalently bound to protein was determined in Novikoff hepatoma grown in both riboflavin-deficient and normal chow-fed rats. In Novikoff hepatoma, the incorporation of [14C]riboflavin into covalently bound flavins relative to that into FAD was substantially greater than that in host liver, and the turnover rate of riboflavin was also accelerated in tumor compared with the liver. The magnitude of incorporation of [14C]riboflavin into each of the various flavin fractions was substantially greater in tumors from riboflavin-deficient animals than in tumors from control animals. These data support the hypothesis that in conditions of riboflavin deprivation, Novikoff hepatoma maintains the levels of the physiologically important flavin coenzymes at the expense of the free riboflavin fraction. The incorporation of riboflavin into covalently bound flavins relative to that into FAD is substantially greater in Novikoff hepatoma than in liver. Accordingly, covalently bound flavins are either present in greater amounts or regulated differently in tumor than in normal tissue. Because the flavin moiety cannot be reutilized, the covalently bound flavin fraction in Novikoff hepatoma theoretically should be able to sequester riboflavin and thereby deplete the body reserves of this vitamin when dietary intake is marginal.

Animals↗
PubMed1987

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

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 [14C]riboflavin or [14C]FAD was added with either ethanol or isocaloric sucrose solutions. Ethanol markedly diminished the bioavailability of [14C]FAD to a greater degree than that of [14C]riboflavin. Corroboration of an ethanol-impaired intraluminal hydrolysis of FAD was provided by using everted jejunal segments and measuring mucosal uptake of [14C]riboflavin 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.

Acetaldehyde↗
PubMed1987

Drugs that promote renal excretion of riboflavin.

Enhanced urinary excretion of vitamins induced by drugs is a major factor in development of vitamin deficiencies. In addition to increasing urinary excretion, drugs can induce vitamin deficiencies by altering their intestinal absorption, transport, storage, and/or metabolic conversions. Aside from drugs, other factors known to influence urinary excretion of vitamins include the level of the vitamin in the diet, the degree of tissue saturation of the vitamin, and the extent of protein binding of the vitamin. Alterations in various aspects of flavin metabolism have been observed following administration of certain drugs, namely, antimalarial, antimicrobial, anticancer, and some tricyclic antidepressant and antipsychotic agents. Of these drugs, boric acid and its derivatives as well as the antipsychotic agent, chlorpromazine, have been shown to promote riboflavinuria in both animals and man. Boric acid complexes with the polyhydroxyl ribitol side chain of riboflavin and greatly increases its water solubility. Individuals who have accidentally consumed boric acid or one of its derivatives excrete high levels of riboflavin within the first 24 to 48 hours following ingestion. The phenothiazine ring of chlorpromazine and the isoalloxazine ring of riboflavin have a number of structural features in common and have been shown to form a molecular complex in vitro. In animals treated for a 3- and 7-week period with chlorpromazine, urinary levels of riboflavin are twice that of pair-fed, saline-treated animals. Recent studies have extended these findings to humans. The administration of certain agents, either therapeutic or toxic, which enhance urinary riboflavin excretion may be of particular concern for high-risk patients who are already nutritionally compromised because of illness or disease.

Animals↗
PubMed1986

New approaches to the possible prevention of side effects of chemotherapy by nutrition.

In an effort to develop new methods for preventing side effects of chemotherapy, the authors initiated studies to determine whether Adriamycin (doxorubicin) inhibits the metabolism of riboflavin (vitamin B2). Adriamycin has been shown to form a 1:1 stoichiometric complex with riboflavin, as well as to compete for binding to tissue proteins. Adult rats treated with Adriamycin in clinically relevant doses were compared to control animals in ability to convert riboflavin into flavin adenine dinucleotide (FAD), the active flavin coenzyme derivative, in heart, skeletal muscle, liver, and kidney. Rats treated with Adriamycin exhibited diminished formation of carbon 14 (14C)FAD in skeletal muscle to nearly 50% that of controls, and in heart to about 70% to 80% of controls. Under these conditions, (14C)FAD formation in liver and kidney was largely unaffected by Adriamycin. In preliminary studies, riboflavin-deficient animals treated with Adriamycin had accelerated mortality rates compared to those of food restricted controls treated with similar doses of Adriamycin. The data as a whole suggest a potential mechanism for Adriamycin-induced cardiac and skeletal myopathy, i.e., inhibition of synthesis of FAD, a flavin coenzyme which is involved in electron transport, lipid metabolism, and energy generation. These findings in an animal model raise the possibility that defects of riboflavin nutriture, either dietary or drug-induced, may be a determinant of Adriamycin toxicity. Further studies are required to explore the potential for preventing side effects due to Adriamycin by administration of this vitamin.

Animals↗
PubMed1986

Riboflavin.

Riboflavin deficiency diminishes the rate of growth of spontaneous tumors in experimental animals but enhances the carcinogenicity of specific drugs such as the azo dyes, which are degraded by a microsomal hydroxylase system requiring riboflavin. Human esophageal cancer has been epidemiologically associated with riboflavin deficiency, but the precise role of riboflavin in this tumor remains to be defined. Riboflavin nutriture influences epithelial integrity, tissue flavin concentrations, rates of prostaglandin biosynthesis, and glutathione metabolism, each of which may have implications for carcinogenesis.

Animals↗
PubMed1985

Inhibition by chlorpromazine of thyroxine modulation of flavin metabolism in liver, cerebrum and cerebellum.

In livers of adult rats that have been treated with thyroxine, the rate of incorporation of radiolabeled riboflavin into both flavin adenine dinucleotide (FAD) and FAD covalently attached to specific apoflavoenzymes was enhanced markedly. By contrast, thyroxine diminished riboflavin incorporation into FAD in cerebrum and cerebellum but continued to enhance incorporation into the covalently bound fraction of FAD. Diminished net incorporation of riboflavin into FAD in brains of adult rats may reflect increased utilization of this fraction for covalent attachment into specific apoflavoenzymes rather than down regulation of the FAD biosynthetic enzymes, flavokinase and FAD pyrophosphorylase, inasmuch as covalent attachment of FAD occurs subsequent to the formation of FAD. The psychotropic drug, chlorpromazine, over a wide dose range, exerted an inhibitory effect on both incorporation of riboflavin into FAD and the utilization of FAD for incorporation into covalently bound flavoenzymes in liver, cerebrum, and cerebellum. Thus, chlorpromazine inhibition of FAD metabolism occurred regardless of the direction of the thyroxine effect and was compatible with an observed inhibitory effect by this drug upon the flavin biosynthetic enzymes.

Animals↗
PubMed1985

Effects of riboflavin deficiency upon prostaglandin biosynthesis in rat kidney.

The effects of riboflavin deficiency on the activity in vitro of prostaglandin synthetase were determined in rat kidney homogenates. For a period of two to five months, weaning rats were fed either a diet deficient in riboflavin or equal amounts of a diet identical in composition except for the addition of riboflavin at four times the RDA for this vitamin. In further experiments, each group of rats was treated for 10 days with either an inhibitor of cyclooxygenase (flurbiprofen) or buffer. Following sacrifice, prostaglandin biosynthesis in vitro was measured both in the absence and presence of reduced glutathione, and subsequently in the presence of reduced glutathione with and without flurbiprofen. Reaction products were extracted from supernatant solutions with diethylether, and the PGE2 and PGF2 alpha formed were measured by radioimmunoassay. Dietary riboflavin deficiency increased biosynthesis rates in vitro of both PGE2 and PGF2 alpha in rat renal medulla and papilla. When both control and riboflavin deficient rats were treated with flurbiprofen for a 10 day period, PGE2 biosynthesis in vitro was markedly inhibited. This inhibition of PGE2 biosynthesis was partially overcome by the addition of reduced glutathione in vitro. The addition of flurbiprofen in vitro to samples containing reduced glutathione prevented the restoration of PGE2 biosynthesis by the latter. The rate of prostaglandin biosynthesis in kidney homogenates from riboflavin deficient rats remained higher than that of controls with each experimental manipulation. These data in their entirety suggest a possible role for riboflavin in the regulation of renal prostaglandin biosynthesis in the rat.

Animals↗
PubMed1984

Relation of riboflavin nutriture in healthy elderly to intake of calcium and vitamin supplements: evidence against riboflavin supplementation.

The status of riboflavin nutriture was evaluated in 24 healthy elderly female residents of a private, nonprofit facility for the care of ambulatory elderly. Riboflavin intake by history was greater than or equal to the recommended dietary allowances (RDA) for this nutrient in all but three subjects, and the average intake in the group as a whole was 50% greater than the RDA. Confirmatory of the findings by history, the status of riboflavin nutriture was excellent in nearly all subjects as evaluated by urinary riboflavin excretion and erythrocyte glutathione reductase activity coefficient. By contrast, calcium intake was greater than or equal to the RDA in ony four of the 24 subjects. The adequacy of calcium intake was found to depend upon a sufficiently high percentage of the total dietary intake of riboflavin being derived from milk and dairy products. It was observed that individual calcium intakes were less than 80% of the RDA unless 40% or more of the total intake of riboflavin was derived from milk and dairy products rather than from other food sources. In those subjects taking daily supplementation with a single multivitamin tablet containing low levels of riboflavin, the total intake of riboflavin and its urinary excretion were increased similarly, suggesting that even small amounts of riboflavin are not retained by elderly subjects consuming a diet adequate in riboflavin.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1983

Accelerated development of riboflavin deficiency by treatment with chlorpromazine.

The present study was undertaken to determine whether treatment with chlorpromazine accelerates the depletion of tissue stores of flavin adenine dinucleotide during dietary riboflavin deficiency. These investigations derived their impetus from earlier findings that low doses of chlorpromazine in rats fed abundant riboflavin increase urinary riboflavin excretion and reduce hepatic flavin stores. From 6 to 10 days after beginning to feed on a riboflavin-deficient diet, rats treated with chlorpromazine, 2 mg/kg body weight twice daily, had approximately twice the urinary riboflavin excretion of that of pair-fed saline-treated controls. When the riboflavin-deficient diets and chlorpromazine treatments were extended for 3 weeks and the animals killed, FAD levels in liver, kidney, and heart were markedly lower in drug-treated than in saline-treated animals. When studies were extended for 7 weeks, tissue FAD levels in saline-treated animals declined further and were equal to those of chlorpromazine-treated rats after only 3 weeks of dietary deficiency. Thus, chlorpromazine treatment accelerated urinary riboflavin loss and accelerated tissue depletion of FAD levels during dietary riboflavin deficiency. Brain levels of FAD by contrast were relatively resistant to both dietary riboflavin withdrawal and treatment with chlorpromazine. Subsequent studies showed that urinary riboflavin excretion began to increase within 6 hr of treatment with chlorpromazine. It is concluded that significant riboflavin depletion occurs following treatment with low doses of chlorpromazine, both in animals fed a normal diet and in animals fed a riboflavin-deficient diet, particularly during the early stages of deficiency.

Animals↗
PubMed1983

Misuse of hair analysis for nutritional assessment.

The analysis of hair for nutritional assessment has a number of potential pitfalls, which include: (1) contamination by sweat, (2) environmental contamination, (3) influence of previous beauty treatments, (4) critical dependence upon location of the hair sample, (5) paradoxic values depending upon the rate of hair growth, and (6) lack of clear definition of a normal range. The results of measuring metal concentrations in hair even under ideal circumstances may not correlate with those obtained in blood and urine. Long-term exposure to heavy metals, including lead, cadmium, arsenic, and mercury, can be readily identified by hair analysis. Little if any value is derived from a random examination of hair as the sole procedure for nutritional assessment. Nutritional recommendations should not be based on the results of hair analysis alone.

Copper↗
PubMed1983

Nutrition and cancer.

Nutrition and cancer interact at several levels. Both dietary deficiencies and dietary excesses have been linked with changes in prevalence of certain human cancers. With respect to one particular nutrient, riboflavin, a dietary deficiency may decrease the development of spontaneous tumors in experimental animals but increase carcinogenesis due to certain agents. Cancer itself has profound effects upon nutritional status, and neoplastic tissue appears in general to resist dietary deficiency more effectively than normal tissues. Nutrition has a major role in therapy of cancer, but as an adjunct to the treatment plan rather than as an alternative. Parenteral nutrition, either peripheral or total, can provide support that is critically needed when patients cannot eat or swallow, have obstruction or malabsorption, or are otherwise unable to utilize dietary nutrients in adequate amounts. The advent of home parenteral nutrition now provides a means for long-term rehabilitation of cancer patients.

Animals↗
PubMed1983

Nutrition and the health of the elderly. A growing concern for all ages.

At a recent symposium, presentations were made summarizing current knowledge relating the dietary intake of six nutrients, calcium, vitamin D, iron, zinc, folate, and thiamin to health and disease in the elderly. The nutritional concerns of the elderly are becoming Increasingly Important as this population segment grows in size. In evaluating the nutritional status of the elderly, dietary calcium deficiency is emerging as a widespread problem. Alcoholism and the chronic use of certain medications appear to be major causes of specific vitamin and mineral deficiencies. Preventive measures to be maximally effective probably have to be started earlier in life. More research is clearly needed concerning the habits, lifestyles and nutritional requirements of various segments of the elderly population.

Adolescent↗
PubMed1982

Cardiac sensitivity to the inhibitory effects of chlorpromazine, imipramine and amitriptyline upon formation of flavins.

Chlorpromazine, imipramine and amitriptyline, drugs structurally related to riboflavin, each inhibited the formation in vivo of flavin adenine dinucleotide (FAD) from riboflavin in rat heart at 2-5 mg/kg body weight, doses comparable on a weight basis to those used clinically. All three drugs inhibited FAD formation in heart within 5 hr after a single dose of 25 mg/kg. Chlorpromazine under these conditions also inhibited FAD formation in liver, cerebrum and cerebellum. A series of psychoactive agents structurally unrelated to riboflavin did not inhibit flavin formation in the organs tested. These findings indicate that the inhibitory effects of the drugs studied have organ specificity with respect to FAD formation.

Amitriptyline↗
PubMed1982

Nutrition and cancer: state of the art relationship of several nutrients to the development of cancer.

Nutrition and cancer interact in a number of important ways and nutritional factors are increasingly recognized as relevant to both the prevention and treatment of cancer. The role of several nutrients in cancer development is considered briefly here. Deficiency of riboflavin (Vitamin B2) prolongs the survival of tumor-bearing animals, but may accelerate carcinogenesis caused by certain agents, as flavin cofactors are involved in drug and carcinogen metabolism. Deficiency of Vitamin A may enhance the development of tumors of epithelial origin, particularly lung. Evidence is accumulating that Vitamin A and/or its precursors, the B-carotenes, may possibly have an effect in chemoprevention of certain of these epithelial cancers both in animals and in man. The consumption of dietary fat among various nations is correlated closely with increased development of cancers of the breast, colon, and prostate, and possibly of other organs. Studies of migrant populations from Japan to the United States show changes in prevalence of stomach and colon cancer in the direction of the native United States population. Sources of nitrites are of concern because of their potential conversion to carcinogenic nitrosamines. Limitation of the delivery of nitrites may be difficult to accomplish so investigators are exploring the blockade of conversion of nitrites to nitrosamines. Nutrition should not be viewed as the sole means of cancer prevention and treatment but rather as a vital component of any treatment plan.

Animals↗