Vitamin deficient animals

It has been shown by the author that examination of the products excreted after administration of tryptophan to vitamin-deficient animals can give valuable information on the function of that vitamin in tryptophan metabolism (142, 171, 173). When tryptophan is given to the riboflavin-deficient rat there is a large excretion of those substances which lie to the left of line BB in diagram 19 (142, 582). This clearly indicates that this is the step at which riboflavin functions, and this is strongly supported by the fact that riboflavin deficiency can reduce up to ten-fold the conversion of tryptophan to quinolinic acid, whereas similar conversion of hydroxykynurenine is unaffected (385). On the other hand, the excretory pattern... 

Precipitate Factor Elvehjem90 and coworkers found a dietary factor in liver, yeast, and milk, which they called the alcohol-ether precipitate factor. This factor can be adsorbed by activated carbon, but difficulty has been experienced in eluting the active substance. However, when carbon that contained the adsorbed factor was fed to vitamin-deficient animals, good growth was obtained. This suggests that elution In vitro could be accomplished under appropriate conditions. 

Xenobiotic-induced pancreatitis may be accompanied by gross plasma lipid changes that may result from marked changes of carbohydrate metabolism (see Chapter 9). The observation of the presence of gross macroscopic fecal fat content (steatorrhea) can indicate effects on pancreatic function, biliary dysfunction, or intestinal malabsorption. In longer-term studies, malabsorption of fat-soluble vitamins may be reflected by the clinical condition of vitamin-deficient animals. 

The blocking or incomplete antibodies produced in man as a result of the antigenic activity of the Rh factors are also of considerable clinical significance. It, therefore, became of interest to determine whether such incomplete antibodies could be produced in the rat and, if so, in what manner their production might be influenced by vitamin intake (Axelrod and Pruzansky, 1954). In all of our previous work only the complete hemagglutinating antibodies were determined. It is conceivable that those vitamin-deficient animals which failed to produce the complete antibodies might still possess the ability to fabricate the... 

Vitamin deficiency Animal Antigen Effect on antibody formation Reference... 

The definitive data presented in the first section of this chapter have established the fact that antibody response, as measured by the content of circulating antibodies, is diminished in a number of vitamin-deficiency states. It is now pertinent to focus attention upon the mode of action of these vitamins. The highly speculative character of this portion of the chapter is due in large measure to our great ignorance of the precise mechanisms involved in antibody synthesis. Various factors which might conceivably influence the level of circulating antibodies in vitamin-deficient animals will be considered in order in this discussion. 

There have been several papers published which suggest that the synthesis of ascorbic acid is impaired in vitamin-deficient animals, with the conclusion that the action of this or that vitamin is necessary at one stage in the synthetic process. It is appropriate to review briefly here the evidence on which such conclusions are based. 

Calcium-binding protein is not found in the intestinal mucosa of vitamin D-deficient animals. It is synthesized only in response to the presence of a material with vitamin D activity. Thus, using antisemm specific to intestinal calcium-binding protein, a radioimmunodiffusion assay (98) conducted on ... 

Co deficit Everywhere Low content of Co in Podsoluvisols, Podzols, Arenosols and Histosols. The average Co content in plant species is < 5 ppb The decrease of Co content in tissues decrease of vitamin BJ2 in liver (tr.—130 ppm), in tissue (tr.—0.05 ppm), in milk (tr.—3 ppm). Synthesis of vitamin Bi2 and protein is weakened. Cobalt-deficiency and Bj2 vitamin-deficiency. The number of animal diseases is decreasing in raw sheep —cattle — pigs and horses. Low meat and wool productivity and reproduction... 

Epileptiform fits associated with degenerative changes in the myelin sheath of peripheral nerves and spinal cord occur in B6-deficient animals. Lesions in the arteries, resembling those of human atherosclerosis, have been observed in Be-deficient monkeys. Recently, a state of Be deficiency in human infants, characterized by loss of ability to convert tryptophan to nicotinic acid, by impaired growth, convulsions, and hypochromic anemia, has been described, following omission of vitamin B6 from the diet. 

Nicotinate and nicotinamide, together referred to as niacin, are required for biosynthesis of the coenzymes nicotinamide adenine dinucleotide (NAD"") and nicotinamide adenine dinucleotide phosphate (NADP" ). These both serve in energy and nutrient metabolism as carriers of hydride ions (see pp. 32, 104). The animal organism is able to convert tryptophan into nicotinate, but only with a poor yield. Vitamin deficiency therefore only occurs when nicotinate, nicotinamide, and tryptophan are all simultaneously are lacking in the diet. It manifests in the form of skin damage (pellagra), digestive disturbances, and depression. 

Medical personnel who work in affluent areas are unlikely to see large numbers of people with vitamin deficiency diseases. However, certain groups of the population are particularly at risk, such as low-income families and chronically ill patients. The classic symptoms of any vitamin deficiency disease as observed in laboratory animals are often blurred in humans. The clinical picture is often complicated by deficiencies of other vitamins, minerals, calories, and protein and by infections and parasite infestations, which usually accompany longstanding malnutrition. Biochemical, physiological, and behavioral changes can occur in the marginal deficiency state without or before the appearance of more specific symptoms. Since the nonspecificity of these changes makes them difficult to detail, this section focuses on the symptoms associated with individual vitamin deficiency diseases. 

GST inhibition. Methyl chloride extract of the leaf, administered intragastrically to rats at a dose of 3 mg/animal daily for 21 months in DMSO solvent, was active. The rats were divided into two groups one was fed a vitamin A diet, and the other a vitamin A-defi-cient diet. In the vitamin-deficient group, the treatment decreased GST levels in liver and lung vs control and vitamin-fed groups . 

TAs one might predict, mutations in the genes for the subunits of the PDH complex, or a dietaiy thiamine deficiency, can have severe consequences. Thiamine-deficient animals are unable to oxidize pyruvate normally. This is of particular importance to the brain, which usually obtains all its energy from the aerobic oxidation of glucose in a pathway that necessarily includes the oxidation of pyruvate. Beriberi, a disease that results from thiamine deficiency, is characterized by loss of neural function. This disease occurs primarily in populations that rely on a diet consisting mainly of white (polished) rice, which lacks the hulls in which most of the thiamine of rice is found. People who habitually consume large amounts of alcohol can also develop thiamine deficiency, because much of their dietaiy intake consists of the vitamin-free empty calories of distilled spirits. An elevated level of pyruvate in the blood is often an indicator of defects in pyruvate oxidation due to one of these causes. ... 

The nutritional need for accessory food factors was first stated explicitly in 1905-1906, although the influence of diet in preventing or curing some diseases such as scurvy had long been known. The name vitamine was proposed in 1912, but the terminal e was dropped when it was realized that not all these compounds are nitrogenous bases. The vitamins serve as coenzymes in various metabolic processes, and the necessary quantities are usually supplied by an adequate diet or by synthesis by the intestinal flora. Vitamin deficiency can arise from a failure to absorb the compound from the gut. The symptoms of deficiency vary in different animal species, and not all the substances found necessary in other species have been shown to be essential for human nutrition. Vitamins are used for the prevention or cure of deficiency diseases and for some other pathological conditions,... 

Other notable findings concerning vitamin-E deficient animals established hepatic lesions [38-40] and accumulation of lipopigment [41], while addition of the vitamin to the diet of rabbits evoked enhanced immune function [42], These early studies in vitamin E deficiency states in animals produced sufficient diverse and interesting observations to generate much of the data currently available. 

Plasma malondialdehyde-like material, an indicator of lipid peroxidation, is increased in conditions of ischaemia, such as stroke [83, 84] and myocardial infarction [85]. Mitochondria extracted from hearts of vitamin-E-deficient rabbits showed a decreased mitochondrial function and an increased formation of oxygen radicals associated with a reduced superoxide dismutase activity. This was partially reversed by addition of vitamin E in vitro [86]. Measurement of in vitro susceptibility to lipid peroxidation in cardiac muscle from vitamin-E-deficient mice showed a highly significant negative correlation between the concentration of vitamin E and in vitro lipid peroxidation. The results indicate that short-term vitamin E deficiency may expose cardiac muscle to peroxidation injuries [ 87 ]. In rats, treatment for 2 days with isoprenaline increased lipid peroxide activity, as measured by malondialdehyde levels, in the myocardium. Vitamin-E-deficient animals were even more sensitive to this effect, and pretreatment with a-tocopheryl acetate for 2 weeks prevented the effect induced by isoprenaline. The authors [88] propose that free-radical-mediated increases in lipid peroxide activity may have a role in catecholamine-induced heart disease. 

Early work revealed evidence of enhanced prostaglandin synthesis in platelets of vitamin-E-deficient animals [122], and the vitamin is known to inhibit platelet aggregation both in vivo and in vitro [ 123]. Further studies have shown that vitamin E can suppress TXA2 synthesis and enhance PGI2 formation [124-126]. 

Retinoic acid (vitamin A acid), in which the alcohol group has been oxidized, shares some but not all of the actions of retinol. Retinoic acid is ineffective in restoring visual or reproductive function in certain species in which retinol is effective. Flowever, retinoic acid is very potent in promoting growth and controlling differentiation and maintenance of epithelial tissue in vitamin A-deficient animals. Indeed, all-trans-retinoic acid (tretinoin) appears to be the active form of vitamin A in all tissues except the retina, and is 10- to 100-fold more potent than retinol in various systems in vitro. Isomerization of this compound in the body yields 13-n.v-rctinoic acid (isotretinoin), which is nearly as potent as tretinoin in many of its actions on epithelial tissues but may be as much as fivefold less potent in producing the toxic symptoms of hypervitaminosis A. 

As might be expected, lipid hydroperoxides are more toxic in vitamin E-deficient animals (H). In the rabbit, the LD Q for... 

Radical scavengers such as a-tocopherols prevent oxidative degradation of HA. In tissue culture systems, the addition of Vitamin E to the medium prevents spontaneous degradation of HA,272 as does superoxide dismutase. In Vitamin-E-deficient animals, there is a decrease in GAGs in tissues, including HA 273 This could be reversed by the addition of Vitamin E to diets,274 suggesting that tocopherol supplements can enhance HA in human skin. 

Cyanocobalamine is a component of several coenzymes and has an effect on nucleic acid formation through its action in cycling 5-methyl-tetrahydrofolate back into the folate pool. The most important dietary sources of the vitamin are animal products. Vitamin Bl2 is also produced by many microorganisms. It is not surprising that vitamin B12 deficiency of dietary origin only occurs in vegetarians. 

The obsolete International Unit (iu) of vitamin A activity was based on biological assay of the ability of the test compound to support growth in deficient animals (1 iu = 10.47 nmol of retinol = 0.3 //g of free retinol or 0.344 //g of retinyl acetate). 

During the development of vitamin A deficiency in experimental animals, the plasma concentration of RBP falls, while the liver content rises. The administration of retinol to deficient animals results in a considerable release of holo-RBP from the liver. This is a rapid effect on the release of preformed apo-RBP in response to the availability of retinol, rather than an increase in the synthesis of the protein. There is no evidence that retinol controls the synthesis of RB P (Soprano et al., 1982). This provides the basis of the relative dose response (RDR) test for liver stores of vitamin A (Section 2.4.1.3) administration of a test dose of retinol gives a considerably greater increase in plasma retinol, bound to RBP, in deficient subjects than in those with adequate liver reserves, because of the accumulation of apo-RBP in the liver. 

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