Effect Of Thiouracil Research Articles

The effects of thiouracil, alloxan and nicotine on the suprarenal glands.

The effects of thiouracil, alloxan and nicotine on the suprarenal glands.

Effects of Thiouracil and Sitosterol on Diet-Induced Hypercholesterolemia and Lipomatous Arterial Lesions in the Rat

Effects of Thiouracil and Sitosterol on Diet-Induced Hypercholesterolemia and Lipomatous Arterial Lesions in the Rat Nutrition Reviews, Volume 18, Issue 1, January 1960, Pages 26–27, https://doi.org/10.1111/j.1753-4887.1960.tb01635.x Published: 01 January 1960

Effect of thiouracil in modifying folate function in severe vitamin B 12 deficiency

The effects of thiouracil in correcting defects in folic acid function produced by B 12 deficiency were studied. Addition of the thyroid inhibitor, thiouracil, to a low methionine diet containing B 12, increased the oxidation of [2- 14C]histidine to carbon dioxide, and increased liver folate levels. Addition of 10% pectin to the diet accentuated B 12 deficiency as evidenced by a greatly decreased rate of histidine oxidation (0.19%) and an increased excretion of methylmalonic acid. Addition of thiouracil to the diet restored folate function as measured by increased histidine oxidation and increased liver folate levels similar to that produced by addition of methionine to a B 12-deficient diet. Thiouracil decreased methylmalonate excretion, and increased hepatic levels of B 12 in animals on both B 12-deficient and -supplemented diets. Hepatic methionine synthase was increased by thiouracil, which may be the result of the elevated B 12 levels. S-Adenosylmethionine and the enzyme methionine adenosyltransferase were also increased by thiouracil. Thus it is possible that the effect of thiouracil in increasing folate function consists both in the effect of thiouracil in decreasing levels of methylenetetrahydrofolate reductase, and also in its action in increasing S-adenosylmethionine which exerts a feedback inhibition of this enzyme.

Effect of Thiouracil on Response to Heat Stress of White Leghorn Lines Selected for Fast and Slow Gain in Two Temperatures

Four lines of White Leghorns previously selected for fast and slow gain from 5 to 9 weeks of age in a hot (32.2 C) and in a cold (21.1 C) selection environment were grown from 5 to 9 weeks in the same two temperature environments. Samples of 32 females from each line of the third generation grown in each temperature environment from 5 to 9 weeks of age were divided into two groups; one received .2% thiouracil in the diet for a 5-day period and the other did not. The temperature was then increased to 40.6 C until 52.8% of all birds had died. The percentages of mortality of lines, rearing environments, and thiouracil treatments were then analyzed. An increase of 64.8% mortality from acute heat stress for birds reared in the cold environment was significant, but the differences among the four selected lines were not. The presence of thiouracil in the diet significantly reduced mortality from heat stress by 16.4%. There were no significant interactions between thiouracil treatments and selected lines or rearing environments.

The Effects of Thiouracil and Thyroxine on Resistance to Heat Shock

Adult White Plymouth Rock hens were submitted to a heat shock of 42.2 C. It was demonstrated that .1% thiouracil fed for 4 weeks prior to heat stress significantly increased survival time. Administration of DL-thyroxine administered at the rate of 4 μg/100 g body weight injected on day of testing did not alter suvival time. However, survival under heat shock was significantly reduced if DL-thyroxine was administered daily for 3 days prior to testing. White Rocks exhibited significantly longer survival time under heat shock than Single Comb White Leghorns, and females of both breeds exhibited significantly longer survival time than their male counterparts. Treatment with DL-thyroxine greatly reduced the survival time differences between breeds and sex. The implications of these findings for applied breeding programs are discussed.

Mechanism of inhibition of iodothyronine-5′-deiodinase by thioureylenes and sulfite

Previous studies have demonstrated that thiouracil inhibits the 5′-deiodination of 3,3′,5′-triiodothyronine uncompetitively with respect to substrate and competitively with respect to cofactor (thiol compounds). This paper shows that sulfite is also a strong inhibitor of this reaction showing a dose-dependent effect between 1 μM and 1 mM. The mode of inhibition is similar to that described for thiouracil. Dose-dependent inhibition was also observed with thiosulfate (0.01–1 mM), iodide and thiocyanate (both greater than 1 mM). No effect was exerted by up to 10 mM cyanide and up to 100 mM azide. Methimazole and thiourea were weak inhibitors above 0.1 mM but inhibition did not reach completion. These experiments were carried out in the presence of 1 mM dithiothreitol. The effect of thiouracil was found to be competitively obviated by methimazole and thiourea. However, the effeft of sulfite and that of methimazole or thiourea were additive. It is proposed that an enzymesulfenyl iodide is formed during deiodination (ping-pong mechanism). This sulfenyl iodide may be reduced by cofactor to yield native enzyme. It may also react with thioureylenes, yielding mixed disulfides, or with sulfite, yielding a thiosulfate. The enzyme-methimazole disulfide is apparently less stable than the enzyme-thiouracil complex. It is suggested that sulfite also reacts with the enzyme-thioureylene disulfide.

Effect of thiouracil upon canine arterial elastic tissue

Unlike some other mammalian species, the dog is relatively resistant to the development of elevated levels of serum cholesterol after prolonged cholesterol feeding. This may be overcome by suppressing thyroid activity with thiouracil. Information regarding possible activity of thiouracil itself upon the arterial tissues is almost nonexistent. The present investigation was undertaken to test whether this drug has any such action, especially upon the arterial elastic tissues. Destructive changes were observed in arterial elastic tissues in dogs given thiouracil for three and six months. The changes consisted of accentuation of the elastic fibrillar components, formation and subsequent coalescence of clefts, and fragmentation and ultimate “dissolution” of the elastic elements. The results suggest that thiouracil may exert a damaging effect upon the arterial elastic fibers; thus, it is possible that one of the mechanisms by which thiouracil and cholesterol administration induces experimental atherosclerosis in the dog is by elastic tissue destruction, possibly promoting the subsequent lipid accumulation in the arterial wall.

Resistance Potential of Certain Breeds of Domestic Fowl Exposed to Raillietina tetragona Infections: 8. Effect of Thiouracil on R. tetragona Infections.

Daily administration of 0.1% thiouracil [4(6) methyl-2 thiouracil Fluka AG] along with the feed to twenty 2-week old chickens belonging to four breeds for a period of six weeks (in a study involving 60 birds) showed no significant effect on the fowl-R. tetragona relationship. We found that the drug has neither lowered nor increased resistance of chickens to this cestode infection. In all the experimental birds, the thyroid gland was enlarged 3–10 times due to hypertrophy and hyperplasia. Hypertrophic changes of thyroid gland and a decrease in leucocyte values observed in infected controls were aggravated in most of the drug-treated experimentals. Breed difference was clearly noticed as regards worm development, haemoglobin values, weight of worms and thyroid glands and percentage of body weight gains in host birds.

The effect of thiouracil on the viability of eggs and embryogeny in Pteridium aquilinum

Gametophytes of Pteridium aquilinum fed for six days with 50 and 75 p.p.m. thiouracil ceased to produce archegonia, but archegonia already initiated completed their development. Eggs produced in the presence of 50 p.p.m. thiouracil were viable, but embryogenesis was retarded. Gametophytes fed with 75 p.p.m. thiouracil mostly remained barren after insemination, the eggs being inviable, but others produced outgrowths from the archegoniate region which were either gametophytic, or sporophytic with a tendency to revert morphologically and functionally to gametophytic tissue.Thiouracil administered after fertilization either prevented embryogenesis, or retarded it, the sporophytes then being deformed and often showing a tendency to produce gametophytic tissue. The embryo became less sensitive to short periods of thiouracil as it developed, possibly because of the appearance of relatively quiescent regions, serving as reservoirs of unaffected cells.The results are held to support the view that the genes responsible for sporophytic growth become activated during oogenesis, and that the cytoplasm of the mature egg already contains the information leading to this kind of growth.

Effects of thiouracil on testicular regression, thymus weights, and molt in pheasants

Administration of 0.1% (by weight) thiouracil in the diet of adult male pheasants ( Phasianus colchicus) from the peak to the end of their breeding season (2–3 months) caused the growth of large goiters, but had no observable effect on normal regression of their testes. No significant differences ( P > .05) occurred in body, testis, adrenal, or anterior pituitary weights nor in total gonadotropin content of the pituitaries between thiouracil-treated and control birds. Thymus weights differed significantly ( P < .02) between treated and control groups, being smaller for the former. Thiouracil had no effect on the progression of the postnuptial molt of primary feathers.

Thiouracil-Induced Elastic Tissue Degenerative Changes in Canine Arteries

Unlike other animal species, the dog is relatively resistent to develop hypercholesterolemia and atheromatous lesions even after long periods of cholesterol feeding. This difficulty is, however, eliminated if the thyroid activity is suppressed surgically or pharmacologically. The most common procedure employed is thiouracil administration. During the course of our studies on the response of the vascular wall to various stimuli, it was of interest to assess the possible effects of thiouracil on the mural elements, since information on the subject is almost nonexistent. In this presentation reference will be made only to changes of the internal elastic lamina (IEL) observed in the carotid and femoral arteries of two mongrel young dogs fed purina chow supplemented by thiouracil (100/mg/kg/day) for 3 and 6 months respectively.The earliest change appeared to consist of an accentuation of the filamentous components of the IEL, formation of fissures or clefts partially filled with a fine fibrillar electron dense material (Fig. 1), and loose bundles of collagen fibrils (Fig. 2). At a later stage, large areas of IEL have a “spongy” appearance with numerous clefts and rarefied areas present.

Effect of Thiouracil on Free Amino Acids in the Blood Plasma of Chicks ,

LEVELS of free amino acids as determined in the blood plasma of chicks can be quite variable even though the chicks are fed similar diets and are of the same breed, sex and age (Shao and Hill, 1967; Hill and Olsen, 1963). An unusually high level of lysine and threonine observed in an experiment in which blood was sampled under conditions of extremely high summer temperature (Hill and Olsen, 1965), prompted us to consider the possibility that the metabolic rate of the bird at the time of sampling might influence plasma amino acid levels. As a test of this hypothesis we measured the plasma amino acids following administration of thiouracil at a level which might be presumed to lower metabolic rate (Singh and Shaffner, 1950; McCartney and Shaffner, 1950, 1949; Shaffner and Andrews, 1948). Although the observations in the present paper did not support the above hypothesis they are believed .

The effect of thiouracil, excess thyroxine and thyroidectomy on the ependymal cells with special reference to the sub-commissural organ.

AbstractThe effects of excess thyroxine, thiouracil and thyroidectomy upon the ependymal cells of the subcommissural organ, the choroid plexus and the wall of the caudal part of the third cerebral ventricle in the adult male albino rats were studied. A total of 203 rats were used. Thiouracil and thyroxine were administered orally, thyroidectomy was performed by means of radioiodine. Thiouracil was seen to diminish the ependymal nuclear volume especially in the subcommissural organ and in the wall of the third ventricle. Similar effects were observed by thyroidectomy, though the change was significant only in the ependyma covering the wall of the third ventricle. Excess thyroxine, again, increased nuclear volume of all ependymal cells studied. The changes could be observed over a period of 4–18 days. The signs of a return to normal after withdrawal of thyroxine and thiouracil were perceived after four days. Visual estimation revealed no clear change in aldehyde‐fuchsin‐positive “secretory material” in the subcommissural organ of any test group. The functional significance of the results is discussed.

Effects of thiouracil on rat liver alpha-glycerophosphate dehydrogenase and serum PBI responses to L-thyroxine.

The effects of dietary thiouracil (TU) were studied on rat liver mitochondrial α-glycerophosphate dehydrogenase (GPD) and serum protein bound iodine (PBI) responses to l-thyroxine (T4) given by sc injection or by gavage. Although serum turnover rates of a single dose of 131I-T4 were not affected by TU, the half-life of serum PB131I averaged 22 hr for injected and 30 hr for gavaged animals. Maximum serum PB131I levels were reached in 8–10 hr in all groups following a single dose of 131I-T4 but the PBI levels were approximately 3 times higher in injected than in gavaged animals. This observation correlates with the previous finding that injected T4 is approximately 3 times more active than oral T4 in the rat. In all experiments, graded doses of T4 given to rats receiving 0.2 g TU/100 g diet resulted in high PBI levels (up to 100 μg/100 ml serum) but suboptimal GPD responses. When the amount of TU in the diet was increased from 0 to 0.8 g/100 g diet, animals receiving 9 μg T4/100 g body weight/day showed a p...

The effect of thiouracil, excess thyroxine and thyroidectomy on the ganglion cells in the region of the paraventricular nucleus of the rat

The effect of thiouracil, excess thyroxine and thyroidectomy on the ganglion cells in the region of the paraventricular nucleus of the rat

Branchiostoma lanceolatumlarvae: Some experiments on the effect of thiouracil on metamorphosis

Larvae ofBranchiostoma lanceolatum(Pallas), of a late pre-metamorphosis stage and characterized by a bright fluorescent green around the ilio-colonic ring, were taken in the Plymouth area plankton in August 1965.Adults were kept in 0.04% thiouracil to determine the general effect at this concentration. It was lethal over a period of weeks.The larvae were kept in the dark at a constant temperature of 10° C, individu-ally or in pairs, in 0.04%, 0.02%, 0.01%, 0.005% and 0.0025% thiouracil, in saturated solutions and suspensions of thyroxine and triiodothyronine, and in ordinary sea water. Solutions were changed weekly. The flagellateDunaliella primolectaButcher was supplied as food.All the larvae metamorphosed at approximately the same time and rate, two exceptions being that 0.04% thiouracil was a more obviously toxic concentration and the thyroxine and triiodothyronine larvae were rather more precocious in their metamorphosis.It is suggested that metamorphosis is a ‘triggered’ process and is self-sustaining. Thus once it has begun it cannot be delayed or accelerated significantly. All the larvae caught were at a stage when this ‘triggering’ had been released.It is considered possible that the metabolism of the larva and the initiation of metamorphosis is controlled by a secretion of the club-shaped gland.INTRODUCTIONThe position of the amphioxides larva has already been discussed (Wick-stead, 1964). No clear demarcation could be made between the usual type of acraniate larva and amphioxides. It was suggested that the amphioxides was a giant larva, a phenomenon not uncommon in oceanic plankton.IntroductionThe position of the amphioxides larva has already been discussed (Wickstead, 1964).

The effect of thiouracil and excess thyroxine on the hypothalamus of the rat with special reference to neurosecretory phenomena.

A study was made of the effects of thiouracil and excess thyroxine on the hypothalamus of the male rat. Measurements were taken of the area of the cross-sections of nuclei in the ganglion cells of sixteen hypothalamic nuclei and areas. At the same time study was made of variations in the distribution and amount of aldehyde-fuchsin-positive neurosecretory material in the different parts of the neurosecretory system. The investigation covered the development and restoration phases of change brought about by both thiouracil and excess thyroxine.

The effects of thiouracil and thyroxine on the host--parasite relationship of Amplicaecum robertsi Sprent & Mines, 1960, in the mouse.

When infected with equal numbers of eggs of Amplicaecum robertsi normal male mice harboured more larvae than normal females. Treatment of the mice with thiouracil and thyroxine eliminated the differences between the sizes of the worm populations shown between the sexes in normal mice.Thiouracil treatment increased the susceptibility of mice to A. robertsi infection, but caused a stunting of the larvae. Thyroxine treatment had no effect on the host–parasite relationship.It is suggested that the differential ability of the larvae to hatch, penetrate the tissues of the host and migrate to the liver in thiouracil- and thyroxine-treated mice was responsible for the differences in the sizes of the larval populations observed.This investigation was carried out during the tenure of a Senior Research Fellowship from the Wool Research Board of Australia. I should like to thank Professor J. F. A. Sprent for his continued interest and Mr C. Wilkinson for his careful assistance.

THIOURACIL-PYRIMIDINE RELATIONSHIPS IN THYROID AND OTHER TISSUES.

An examination was made of several systems in which thiouracil and the pyrimidines, uracil, thymine and orotic acid, might compete. The goitrogenic effects of thiouracil were compared with those of other thiopyrimidines and thiopurines. Only thiopyrimidines exhibited goitrogenic properties with thioorotic acid and thiocytosine being weakly goitrogenic and thiothymine inactive. The goitrogenic properties of thiouracil in an iodine-deficient diet were not reduced by simultaneous administration of daily doses of uracil or thymine 300 and 120 times, respectively, that of thiouracil. The pyrimidines and thiouracil were not degraded to 14CO2 by rat thyroid or calf thymus slices. Rat liver slices rapidly oxidized uracil-2-14C, metabolized orotic acid-6-14C only slightly, and did not appear to degrade thiouracil at all. The addition of thiouracil had no discernible effect on the degradation of uracil. Utilization of uracil for RNA formation by thyroid slices was not altered by the presence of thiouracil but was d...

EFFECTS OF THIOURACIL AND OF THYROIDECTOMY OF LIVER PROTEIN METABOLISM.

Incorporation of 0.5% thiouracil into an 18% casein diet for 21 days increased both relative (g/100 g body wt) and actual liver weights in mature male rats. However, thyroidectomy decreased liver weights below euthyroid control level. Thiouracil feeding increased protein/DNA ratios above controls; thyroidectomy decreased these ratios. The thiouracil-treated animals had RNA /DNA ratios equal to controls, whereas in thyroidectomized rats they were reduced. The halflives of liver cell protein fractions were estimated using 35S DL-methionine. Both thyroidectomy and thiouracil feeding increased the half-life of total liver protein and most subcellular fractions. However, 35S incorporation indicated that the livers of thyroidectomized rats were synthesizing protein more slowly, which accounts for the reduced liver size. These data suggest that thiouracil feeding for 21 days increases liver size by decreasing the rate of protein catabolism, while not altering the rate of synthesis. Reduced liver size in thyroide...