Pyridoxine-deficient Rats Research Articles

Relative Concentration of Vitamin B12 in the Organs of the Male Rat as Affected by its Intake of the Vitamin

The concentrations of vitamin B12 in certain organs of the male rat were studied under conditions where the animal was deficient in the vitamin and where it was fed ample quantities. The kidneys stored large amounts when an abundant supply was available. The pituitary and the adrenals also contained high concentrations, equal to or not far below those in the kidneys of vitamin B12-deficient rats but much less than those in the kidneys of vitamin B12-sufficient rats. The heart contained fair amounts when the vitamin was supplied. The other tissues studied contained much smaller concentrations, the testes and seminal vesicles having particularly low amounts when the rat was deficient in the vitamin. Rats aged 189 to 301 days differed little from those aged 62 to 77 days of age in respect to the vitamin B12 concentration in their tissues, except for slightly greater storage in a few of the tissues in the older group when the vitamin was administered.

Effect of Chronic Ethanol Ingestion on Liver Enzyme Changes Induced by Thiamine, Riboflavin, Pyridoxine, or Choline Deficiency

The effect of ethanol on riboflavin, pyridoxine, thiamine, and choline deficiencies was studied by measuring changes in rat liver dehydrogenases and by histologic assessment of fatty change in the liver. Ethanol ingestion lessened the changes induced by riboflavin deficiency. A diminution of succinic dehydrogenase (SD) activity was induced by riboflavin deficiency; however, in ethanol-fed rats this activity was significantly less diminished, and the fatty liver observed in the riboflavin-deficient animals was prevented. In contrast, the combination of ethanol ingestion and pyridoxine deficiency caused a reduction in β-hydroxybutyric dehydrogenase (HBD) activity and caused a fatty liver, whereas pyridoxine deficiency alone or ethanol feeding alone did not. Thiamine deficiency decreased the activities of HBD and lactic (LD) dehydrogenases; these depressed levels were unaffected by ethanol ingestion. The combination of choline deficiency and ethanol ingestion decreased the activities of HBD and nicotinamide-adenine dinucleotide phosphate (NADPH) dehydrogenases; however, the activity of NADPH dehydrogenase was also reduced by either choline deficiency or ethanol alone. The data suggest that ethanol ingestion is more deleterious to pyridoxine-deficient rats than to controls.

Increased excretion of formimino-glutamic acid by vitamin B12-deficient rats after a load of DL-homocystine or oxidized glutathione.

Increased excretion of formimino-glutamic acid by vitamin B12-deficient rats after a load of DL-homocystine or oxidized glutathione.

Changes in Fatty Acid Composition in Liver Lipid Fractions of Pyridoxine-deficient Rats Fed Cholesterol

This study was made to determine whether changes in fatty acid patterns of liver phospholipids and sterol esters accompanied the decreases in esterified sterol previously observed in pyridoxine-deficient rats. The diets included: (a) basal casein-5% cottonseed oil-sucrose diet; (b) basal diet plus cholesterol; (c) basal diet plus taurocholate; (d) basal diet plus cholesterol and taurocholate. Cholesterol was added to exaggerate the need for oleate and arachidonate since this stress might provide added information on unsaturated fatty acid metabolism in pyridoxine deficiency. Taurocholate was added to increase cholesterol absorption. These diets, with or without pyridoxine, were fed to male weanling rats for 6 weeks. Food intake of controls was restricted to the food intake of the corresponding deficient groups. Phospholipid tended to be lower in the deficient groups and liver sterol ester was significantly lower. All deficient groups showed a significant decrease in oleate in all lipid fractions, compared with their respective controls. Arachidonate and linoleate were significantly higher in sterol esters in all deficient groups. It was concluded 1) that pyridoxine deficiency significantly alters the metabolism of dietary and endogenous cholesterol and 2) that decreases in monoenoic acids in pyridoxine deficiency may be related to insulin insufficiency.

Some Effects of Vitamin B6 Deficiency on Rat Pituitary Glands

Vitamin B6-deficient rats, compared with controls showed a marked decrease in pituitary levels of growth hormone. The administration of ovine growth hormone over a 10-day period resulted in a significant growth response in vitamin B6-deficient rats and a large increase in the response of their epididymal fat pads to insulin. Control rats were not significantly affected. The results of tissue vitamin B6 analyses and studies of the uptake and loss of tritium after injection of tritiated pyridoxine indicate that the vitamin B6 content of rat pituitaries is high when compared with other tissues and that it is rapidly depleted when a vitamin B6-deficient diet is fed.

Renal concentrating ability in pyridoxine deficiency.

SummaryPyridoxine deficiency was induced in rats by feeding a diet deficient in pyridoxine. Control rats were pair-fed to the intake of the experimental group. Pyridoxine deficiency was demonstrated in the experimental group by increased xanthurenic acid excretion following a tryptophane load and by development of hypertension. Renal concentrating ability, measured as maximum urinary osmolality following dehydration and vasopressin administration, was impaired in both pyridoxine deficient and control rats. Since both groups were protein depleted as a result of the pair-feeding, urea was given to both groups and renal concentrating ability remeasured. The control group now had normal concentrating ability, whereas the maximum urinary osmolality of the pyridoxine deficient rats was significantly reduced. These results suggest that pyridoxine or some aspect of its metabolism is essential for normal renal concentrating ability.

Effects of pyridoxine deficiency on the adaptation of rat liver cystathionase to DL-ethionine and to thyroidectomy.

THE activity of liver cystathionase (‘soluble’ cysteine desulphydrase) of rats is adaptively increased both after thyroidectomy1 and after feeding DL-ethionine2. Since pyridoxal phosphate (PLP) is the co-enzyme of cystathionase3, it was of interest to determine the effect of pyridoxine deficiency on the level of liver cystathionase. Experiments were also conducted to determine the adaptive increase of cystathionase in pyridoxine-deficient rats in response to thyroidectomy and to ethionine feeding.

ZINC CONTENT IN TISSUES OF PYRIDOXINE DEFICIENT RATS.

SummaryPyridoxine deficiency in rats resulted in a decreased Zn content in the plasma, liver, pancreas, and heart tissues and an increase of Zn-65 uptake in the plasma and liver after an intramuscular injection of radiozinc. A highly significant increase in Zn-65 radioactivity was also observed in the gastrointestinal tract and feces of pyridoxine-deficient rats. This phenomenon appeared to be specific for pyridoxine since deficiency of thiamine or riboflavin did not affect hepatic Zn concentrations.

Effect of pantothenic acid and vitamin B6 on the excretion of taurine in the urine of rats.

Amount of taurine has increased in urine of rats fed on pantothenicc acid-deficient ration. In contrast, it has decreased in pyridoxine-deficient rats. The increase in pantothenic acid-deficient rats might be resulted from hyperfunction of adrenals and the decrease in vitamin B6-deficient rats would be due to lowered activity of evsteinsulfinic acid decarboxvlase in liver.

Effect of Pyridoxine Deficiency upon Polysomes and Messenger RNA of Rat Tissues

Relation of the role of pyridoxine in nucleic acid metabolism to its function in protein biosynthesis has been investigated. Sedimentation patterns of RNA pulse-labeled with orotic-6-C14 acid have been determined in a linear sucrose gradient. With this procedure, a decreased incorporation of labeled orotic acid into the 29S and 18S components of ribosomal RNA and into messenger RNA was observed in liver of pyridoxine-deficient rats. The decreased synthesis of these components of RNA, particularly messenger RNA, was related to the decrease in number of polysomes per unit weight of liver and spleen observed in this deficiency and the resultant decreased capacity of ribosomal preparations from these deficient tissues to incorporate labeled leucine and valine in vitro. These observations on the mode of action of pyridoxine in protein biosynthesis formed the basis for an explanation of the adverse effects of a pyridoxine deficiency upon the development of immune phenomena.

Comparative metabolism of D-and L-3,4-dihydroxyphenylalanine in normal and pyridoxine-deficient rats.

Comparative metabolism of D-and L-3,4-dihydroxyphenylalanine in normal and pyridoxine-deficient rats.

IN VITRO EFFECT OF ADRENAL STEROIDS ON CARBOHYDRATE SYNTHESIS IN LIVER OF PYRIDOXINE-DEFICIENT RATS.

Adrenal steroid hormones stimulate hepatic gluconeogenesis when administered in vivo or when incubated with liver slices in vitro. The steroids also cause increased activity of the liver glutamic pyruvic transaminase (LGPT), and it has been postulated that this is the mechanism through which the hormones alter carbohydrate metabolism. To test this hypothesis, the effect of adrenal steroids on carbohydrate synthesis in liver slices from pyridoxine-deficient rats was determined since pyridoxal phosphate is coenzyme for the LGPT. Effect of the hormones on gluconeogenesis in pyridoxine-deficient liver tissue was equal to that observed previously in normal rat liver and was greater than that which occurred in liver of pair-weighed controls. These findings suggest that increased carbohydrate formation which is induced by adrenocortical hormones may be unrelated to the effect of the steroids on LGPT activity (Endocrinology 74: 742, 1964)

Carbohydrate and Fat Metabolism and Response to Insulin in Vitamin B6-deficient Rats

Vitamin B6-deficient rats, compared with appropriate controls, showed growth inhibition, and a decrease in total carcass lipids. The palmitoleic acid content of the liver and epididymal fat pad lipid decreased and the content of stearic and linoleic acids increased. All of these changes were partially prevented by insulin administration. The deficient animals showed hypoglycemia and a decreased ability to clear glucose from the blood after the administration of glucose, and decreased tolerance to insulin. “Insulin-like activity,” determined by the effect on epididymal fat pads, of the serum and pancreatic tissue was lower than in control animals. The epididymal fat pads of deficient animals were much more sensitive to insulin than those of controls as measured by net gas exchange and incorporation of labeled glucose into fat.

Relationship of Pyridoxine to Immunological Phenomena

Publisher Summary This chapter reviews the present status of the role of pyridoxine in various immunological phenomena and discusses recent experiments conducted in the laboratory dealing with the mode of action of this vitamin. Production of circulating antibodies as well as the state of delayed hypersensitivity is impaired in pyridoxine deficiency. The effect of this deficiency upon a delayed hypersensitivity reaction is illustrated by the prolongation of skin homografts in pyridoxine-deficient rats. The application of this deficiency state in the production of immune tolerance with splenic cells has been demonstrated and its possible clinical value indicated. The chapter describes experiments in which tolerance was achieved by administering ribosomes or RNA to newborn mice and microsomal RNA to adult, pyridoxine-deficient rats. It is hypothesized that specific messenger RNA associated with ribosomes initiates synthesis of donor transplantation antigens within the host. Pyridoxine deficiency again functions to provide in the adult the necessary state of immunological inertness that is already present in the newborn. Clinical application of such cellular components involved in synthesis of specific proteins, as well as utilization of the transplantation antigens themselves, has been projected.

Vitamin B6 in Fat Metabolism

This chapter discusses the conflicting data on the relationship of the vitamin B 6 group, especially pyridoxine, to only a few of the many aspects of fat metabolism. The fatty acid composition of adipose tissue of pyridoxine-deficient rats is different from normals and that injections of insulin tended to reverse these changes. Pyridoxine-deficient rat serum and pancreatic tissue had lowered levels of insulin as measured by the epididymal fat pad method for insulin-like activity. Such evidence suggests that the lipid changes in pyridoxine-deficient rats might be related to the more complex relations of insulin insufficiency to fat metabolism. Indirect pathway is suggested by which fat metabolism can affect the utilization of vitamin B 6 and vice versa. The chapter mentions the known relationships between phospholipids and cholesterol esters on the one hand and fatty acid transport on the other.

STUDIES ON SPECIFICITY OF ACTION OF RIBONUCLEIC ACID EXTRACTS UPON VIABILITY OF SKIN HOMOGRAFTS IN THE RAT.

SUMMARY Administration of splenic microsomal RNA extracts to pyridoxine-deficient rats had been previously shown to increase viability of subsequent skin homografts. The following observations on the specificity of action of splenic extracts have been made: (1) treatment of splenic microsomal RNA extracts with ribonuclease or alkali destroyed their ability to prolong viability of skin grafts; (2) splenic microsomal RNA extracts administered in combination with splenic extracts prepared from the mitochondrial or soluble fractions had no beneficial effect; (3) an RNA extract obtained from a rat of genetic strain other than that of the skin donor was ineffective; and (4) microsomal RNA derived from the spleen of the skin donor failed to increase viability of the skin graft when administered to a normal recipient.

Behavioral thermoregulation during vitamin B6 deficiency.

Thermoregulatory behavior was studied in vitamin B6-deficient and control rats exposed to a temperature of 2–3 C. The animals were kept in an experimental chamber provided with a lever which, when pressed, turned on a heat lamp placed above the chamber. The B6-deficient rats turned on the heat lamp more frequently than did the controls. This difference was observed with both ad libitum and paired feeding. Furthermore, administration of vitamin B6 to the deficient rats and deoxypyridoxine, a B6 antagonist, to the controls brought about reversals in the relative frequency of heat reinforcements which were accompanied by changes in biochemical indices of vitamin B6 deficiency, i.e., increased xanthurenic acid excretion and decreased plasma glutamic-oxalacetic transaminase levels. Measurements of skin and rectal temperatures in the cold indicate that the body temperature of B6-deficient rats falls more rapidly than that of controls, a fact which would account for the difference in thermoregulatory behavior. Attempts to search for evidence of thyroid dysfunction in B6-deficient rats as the possible cause of such behavioral differences were unrevealing. These experiments indicate that behavioral studies are useful in assessing nutritional deficiency.

Interrelations among Magnesium, Vitamin B6, Sulfur and Phosphorus in the Formation of Kidney Stones in the Rat

Dietary levels of magnesium, sulfur and phosphorus have been shown to affect markedly the excretion of a variety of urinary constituents and to influence the deposition of renal calcium oxalate in vitamin B6-deficient rats. Diets high in magnesium or low in sulfur-protected rats against stone formation. The protective effect of high magnesium diets was interfered with when the diets were also low in phosphorus even though there was a decrease in the hyperoxaluria associated with vitamin B6 deficiency. Apatite nephrocalcinosis was observed in rats receiving high phosphorus diets containing vitamin B6 and 0.04% of magnesium. In vitamin B6-deficient rats receiving diets high in phosphorus and containing 0.4% magnesium, renal calculi composed of calcium oxalate and calcium phosphate were formed.

Erythrocyte Survival of Rats Deficient in Vitamin E or Vitamin B6

Rats were fed diets deficient in vitamin E or B6, and the characteristic changes in growth rate, urinary creatine-to-creatinine ratios, and urinary xanthurenic acid output were observed. The maximal erythrocyte survival of rats fed a vitamin E-deficient diet for 138 days was less than values obtained from replete animals, as determined by the Cr51 method. After the diet was fed for 265 days, the difference was even greater. The bodies and organs of vitamin E-deficient rats contained more Cr51 than those of replete controls. Vitamin B6 deficiency resulted in a small, but significant, increase in maximal survival time of erythrocytes. Whole-body Cr51 determinations did not reveal a difference between vitamin B6-deficient and replete rats. The significance of these results is discussed in relation to blood destruction and sequestration in the reticuloendothelial system.

Glutamic Oxalacetic Transaminase Activity in the Ovary of Hypothyroid and Vitamin B6Deficient Rats

The effect of serum gonadotrophin (PMS) in stimulating glutamic-oxalacetic transaminase (GOT) activity in the ovary and uterus of rats was shown to be dependent on the reactivity of the ovary to gonadotrophin stimulation. In vitamin B6 deficient rats, in which the reactivity of the ovaries is lowered, even a dose as large as 40 IU of PMS does not change the low GOT activity of the ovary and uterus. On the other hand, in thiouracll-fed rats, in which the ovarian reactivity to gonadotrophin stimulation is enhanced, the stimulating effect of PMS on GOT activity is markedly increased. The deleterious effect of vitamin B6 deficiency on GOT activity is rapidly reversed after placing the rats for 5 days on normal diet.