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PubMed1977

Effect of anti-thyroid agents, methimazole and propylthiouracil, on brain noradrenaline content.

1 Methimazole (1-methyl-2-mercaptoimidazole, MMI) and propylthiouracil (6-propyl-2-thiouracil, PTU) which are used in the therapy of hyperthyroidism were found to reduce brain noradrenaline (NA) content. Endogenous NA levels in rat brain were reduced from 1 to 6 h after intraperitoneal injection of MMI by doses in excess of 25 mg/kg and by PTU at a dose of 50 mg/kg. However, endogenous NA in the rat heart was only slightly reduced after 50 mg/kg of MMI, and was not affected by PTU (50 mg/kg). 2 Both MMI and PTU effectively inhibited the in vivo conversion of [3H]-dopamine into [3H]-noradrenaline ([3H]-NA) in the brain of rats after a single intraperitoneal injection of doses above 10 mg/kg (MMI) and 25 mg/kg (PTU). This inhibition by MMI and PTU was dose-dependent over the range of 10 mg/kg to 50 mg/kg, was highest after 2-3 h and continued for at least 6 h after their injection; The conversion rates returned to normal after 24 hours. 3 The results suggest that the reduction of brain NA by these drugs is, at least in part, due to the inhibition of brain dopamine beta-hydroxylase.

Animals↗
PubMed2001

The incidence and clinical characteristics of symptomatic propylthiouracil-induced hepatic injury in patients with hyperthyroidism: a single-center retrospective study.

OBJECTIVES: Although symptomatic propylthiouracil (PTU)-induced hepatic injury is known to be rare, there have been few reports about its exact incidence in patients with hyperthyroidism. We tried to evaluate its incidence in a single center and its clinical course. METHODS: Medical records of 912 hyperthyroid patients who had been diagnosed between March 1990 and December 1998 were reviewed about clinical characteristics, management, and laboratory findings. Symptomatic PTU-induced hepatic injury was defined as the development of jaundice or hepatitis symptoms with at least a 3-times elevation of liver function tests (LFT) without other causes. RESULTS: Four hundred ninety-seven patients (age 42.6 +/- 10.7 yr, male/female 140/357) were included. Clinically overt hepatitis developed in six patients (1.2%; age, 43.7 +/- 14.8 yr; male:female ratio, 3:3) between 12 and 49 days after PTU administration. Jaundice and itching developed in five patients, fever in two, rash in two, and arthralgia in one. Bilirubin, ALT, and ALP increased in five, four, and six patients, respectively (293 +/- 288 micromol/L, 143 +/- 111 U/L, and 265 +/- 81 U/L; normal, < 117 U/L). The type of hepatic injury was cholestatic in three, hepatocellular in one, and mixed in two patients. None resulted from viral hepatitis. There were no statistical differences in age, sex, PTU dose, or T4 and T3 levels at initial diagnosis between patients with and without hepatic injury. LFT normalized in all patients between 16 and 145 (72.8 +/- 46.4) days after the PTU withdrawal. CONCLUSIONS: Symptomatic hepatic injury develops usually within the first few months of PTU administration with rare frequency, but its clinical course is relatively benign once the drug is withdrawn. However, it may be difficult to predict its development, so all patients should be monitored for rise in LFTs at regular intervals, especially during the early period.

Adult↗
PubMed1983

Potentiation of hepatotoxicity by ethanol in galactosamine-induced hepatitis in rats: role of propylthiouracil protection.

Chronic ingestion of ethanol (5 g/kg/day) for 6 weeks increased the hepatotoxicity of a single injection of D-galactosamine (330 mg/kg) in rats. Plasma transaminases, alkaline phosphatase, gamma glutamyl transpeptidase and sulphobromophthalein retention were consistently high in alcohol-fed rats compared to sucrose-fed controls, 25 hours after galactosamine administration. Liver histology in sucrose-fed rats revealed typical inflammatory changes and cytoplasmic vacuolation without cell necrosis was seen. Propylthiouracil treatment had no beneficial or protective effect in alcohol-fed rats in this animal model of hepatitis.

Animals↗
PubMed1987

Kinetics of radioiodine released from prelabelled thyroid gland in vivo: influence of propylthiouracil.

The kinetics of free and hormone bound blood iodine after stimulation with endogenous thyroid stimulating hormone (TSH) are not satisfactorily characterized. We studied these kinetics in mice injected with 125I and thyroxine. In control mice, the injected 125I is organified within the thyroid and incorporated into thyroid hormones, whereas in mice treated with the thyreostatic drug propylthiouracil (PTU), most 125I remains inorganic, since the thyroperoxidase activity is inhibited by PTU. We found that during blockade of TSH secretion by means of thyroxine, blood 125I activity was significantly higher in PTU-treated animals than in controls, indicating that PTU impaired thyroidal uptake of 125I. On the fourth day after the thyroxine load, the blockade of TSH secretion vanished. This caused the blood 125I activity to increase markedly. The increase of blood 125I was as high in PTU-treated animals as in controls. After the peak, blood 125I was cleared according to first order kinetics, with a half-time of 0.72 days (= 17.3 hours) in PTU-treated animals and of 6.3 days in controls (P less than 0.001). It is suggested (1) that PTU impairs thyroidal uptake of iodide, (2) that endogenous TSH stimulates release from the thyroid of inorganic iodide as well as of thyroid hormones, and (3) that inorganic iodide released by the thyroid has a much shorter biological half-life than hormone-bound iodine.

Animals↗
PubMed1998

PROP (6-n-propylthiouracil) supertasters and the saltiness of NaCl.

Taste blindness to phenylthiocarbamide (PTC) and its chemical relative 6-n-propylthiouracil (PROP) was discovered in the 1930s. Family studies showed that those who could not taste PTC/PROP (nontasters) carried two recessive alleles. In recent years, we have classified tasters into two groups: medium (PROP is moderately bitter) and supertasters (PROP is intensely bitter). With our classification, approximately 25% of Americans are nontasters, 50%, medium tasters, and 25%, supertasters. Studies showed that supertasters form a cohesive group. Anatomical studies showed that supertasters have the most fungiform papillae. Psychophysical studies showed that supertasters perceive the most intense bitterness and sweetness from a variety of compounds, the most intense burn from oral irritants, and the most intense tactile sensations from viscous solutions. Oral burn and touch are presumably perceived to be the most intense to supertasters because taste buds in fungiform papillae are innervated by the trigeminal nerve (pain, touch) as well as the chorda tympani nerve (taste). The psychophysical scaling method used was magnitude matching with NaCl as the control modality. With this method, subjects rated the intensities of a series of NaCl and PROP solutions. The assumption that the taste of NaCl did not vary with PROP status allowed comparisons of the bitterness of PROP across subjects. Early magnitude matching studies, using sound as the control, had suggested that this assumption was reasonable. However, recent studies challenged that conclusion. Larger samples with more diverse populations, using sound as the control, showed that the taste of NaCl varied with PROP bitterness; supertasters perceived the strongest taste and nontasters, the weakest. Thus our earlier conclusions were conservative because differences between nontasters, medium tasters, and supertasters were concealed by using NaCl as a standard. Using magnitude matching with sound as the standard, or using the Green scale, which employs intensity labels, we found that the differences between PROP groups are larger. Note that the association between PROP status and salt taste is interesting in itself, since variability in salt taste may have important nutritional consequences.

Humans↗
PubMed1998

Sensory responses to 6-n-propylthiouracil (PROP) or sucrose solutions and food preferences in young women.

Genetic sensitivity to the bitter taste of 6-n-propylthiouracil (PROP) has been linked with a greater number of food aversions and reported rejection of some bitter foods. Healthy young women (n = 121) were divided into nontasters, tasters and supertasters of PROP according to their PROP detection thresholds and the ratio of intensity ratings of PROP versus NaCl solutions. Hedonic response profiles to sucrose solutions distinguished between likers and dislikers of sweet. All subjects completed a 171-item food preference checklist. Food preference data were reduced by factor analyses, subscales of which were tested for reliability using Cronbach's alpha. Greater PROP sensitivity was associated with lower acceptance of coffee, cruciferous vegetables, tart citrus fruit, dark breads, and selected fats. In contrast, liking for sucrose solutions was linked to liking for sugar in tea and coffee, but not to any special pattern of food acceptance. Strategies aimed at increasing the consumption of grains, vegetables, and fruit should consider the role of inherited taste makers and their potential impact on dietary habits.

Adult↗
PubMed1998

The perceived bitterness of beer and 6-n-propylthiouracil (PROP) taste sensitivity.

Pelchat and Danowski found a significantly higher proportion of nontasters of 6-n-propylthiouracil (PROP) among children of alcoholics than among children of nonalcohlics, suggesting a possible genetic association between alcoholism and PROP tasting ability. They suggested that nontasters may not find alcohol as bitter as tasters do and may be at greater risk for alcoholism because they like the taste of alcoholic beverages more. In the present study we tested this hypothesis by examining how nontasters, medium tasters, and supertasters of PROP judged the taste of two kinds of beer. Forty-seven males and 53 females between the ages of 21 and 49 rated the perceived bitterness of Budweiser and Pilsner Urquell on the oral Labeled Magnitude Scale (LMS). Subjects also rated their degree of liking or disliking for the two beers on a 9-point Likert scale. PROP papers and the LMS were used to classify subjects into tasting groups. The results lent some support to the hypothesis in that male nontasters liked the taste of Pilsner Urquell better than male supertasters, when they tasted Pilsner Urquell after Budweiser. (This finding was not replicated for females). Also, as subjects' ratings of bitterness for the two beers increased, their degree of liking for the taste decreased. Supertasters rated Pilsner Urquell significantly more bitter than medium tasters. Subjects were asked about their drinking habits, and supertasters reported consuming significantly less beer than nontasters when they first started drinking beer on a regular basis. There were no significant differences in current drinking behavior between tasting groups. These results suggest that supertasters are distinct from nontasters with regard to their taste for beer and may to some degree be protected against alcoholism by their dislike for bitter substances.

Adult↗
PubMed1998

Psychophysical measurement of 6-n-propylthiouracil (PROP) taste perception.

The ability to taste 6-n-propylthiouracil (PROP) is genetically determined. PROP tastes moderately bitter to 'medium tasters' (MT), intensely bitter to 'supertasters' (ST), and tasteless to 'nontasters' (NT). The psychophysical method used to characterize PROP status should capture the entire range of perception, while minimizing context, ceiling and other effects. Magnitude estimation successfully captures the variability in PROP perception, but requires normalization and may be difficult to conduct in industrial settings. Two labeled scales were tested as part of three separate studies (S1, S2 and S3) to measure perceived intensity of PROP and sweeteners. All studies included reportedly healthy volunteers aged 21-62 years recruited at Cultor Food Science in Groton, CT. In S1 [n = 163 (55 males, 108 females)], subjects rated perceived intensity of PROP-saturated paper and sucrose (1.0 M) on the Labeled Magnitude (Green) Scale (LMS) [labeled line with descriptors (no taste--strongest imaginable)]. In S2 [n = 152 (49 males, 103 females)], subjects rated perceived intensity of sucrose (1.0 M) and PROP solutions (0.001 M, 0.0032 M) on the LMS. In S3 [n = 136 (48 males, 88 females)], subjects rated perceived intensity of sucrose (1.0 M) and PROP solutions (0.001 M, 0.0032 M) on a 9-point category scale (1 = not at all; 9 = extremely). In all experiments, water rinses were included between each tastant and PROP was the final stimulus. Statistical analyses included descriptive statistics, regression analysis, and ANOVA. In S1 and S2, those with higher PROP perception perceived sucrose more intensely [(S1: r = 0.32; p < 0.001); (S2: r = 0.25; p < 0.01)]. A higher frequency of females were ST than males. Also, the PROP effect on sweet perception was most evident in female ST. This apparent sex difference may be the result of hormonal variation associated with menstruation. As well, in S1 and S2 subjects aged 20-40 years, females had significantly greater variance among sucrose intensity ratings than males (F = 3.66; p < 0.01), which may be due to hormonal changes with menses. The S3 results failed to show either the positive correlation between PROP and sucrose perception or the sex difference. Thus of the two labeled scales, the LMS appears to be better for assessing PROP perception, as it is continuous and also minimizes ceiling effects. Future research will extend these studies by including sucrose and high intensity sweetener concentration series.

Adult↗
PubMed1988

Polymyositis after propylthiouracil treatment for hyperthyroidism.

An additional disorder in the spectrum of thyroid related muscle disease is presented. Hypothyroid and hyperthyroid disease are both associated with a variety of muscle abnormalities, from myalgias to myopathy. Polymyositis, however, has never been reported immediately after treatment for active hyperthyroidism. A patient is presented with typical hyperthyroidism, who developed a severe proximal muscle weakness and a raised creatine phosphokinase after treatment for hyperthyroidism with propylthiouracil (100 mg orally, three times a day). Electromyography, muscle biopsy, and the course of the patient's illness were consistent with polymyositis. Whether this represents a cause-effect association or a chance occurrence is unknown. Physician awareness of the occurrence of a variety of muscle disorders including polymyositis in thyroid disease is emphasised. A brief discussion of thyroid myopathy, thionamide drug reactions, and polymyositis is included.

Adult↗
PubMed1985

Effect of propylthiouracil dose on serum thyroxine, growth, and weaning in young rats.

The antithyroid drug propylthiouracil (PTU) is a potent inducer of hypothyroidism in the rat. To evaluate the effects of PTU on serum thyroxine (T4) concentration, growth, and weaning progression during development, five doses of PTU (0.0001, 0.0005, 0.001, 0.005, and 0.01 g/100 ml) were administered to infant rats via drinking water of the dam. The highest dose, 0.01%, is commonly used in developmental studies. The results indicate that 0.001% PTU creates hypothyroid pups without the debilitating characteristics of pups raised on 0.01% PTU. A second experiment examined the effects of 0.001% PTU on serum T4 concentration, growth, and weaning progression during the fourth postnatal week. Serum T4 concentration was depressed throughout the study period to 25% of controls. The hypothyroid pups continued to grow, although they were significantly smaller than untreated controls. Weaning was initiated by postnatal day 22 and completed on day 29. For normal untreated pups, weaning is initiated by day 17 and completed by day 26. Thus hypothyroidism delays but does not abolish the weaning process.

Animal Population Groups↗
PubMed1986

Propylthiouracil causes phase delays and circadian period lengthening in male and female hamsters.

The thyroid neuroendocrine axis has been implicated in the control of circadian rhythmicity. The present work examined the ability of a thyroid hormone-inhibiting agent, propylthiouracil (PTU), to modulate phase and period of the hamster wheel-running circadian rhythm. The circadian period (tau) of blind male hamsters was lengthened by approximately 0.2 h when they were fed a diet containing 0.6% PTU. Removal of the PTU reversed the change in tau. Pinealectomy did not alter the tau response to PTU. Blind ovariectomized female hamsters showed changes in tau during and after PTU treatment that were similar to those of males. Males were also tested with 0.3, 0.6, or 1.2% PTU diets, and a dose-response relationship was established. Under 14:10 light-dark (LD 14:10) conditions, the phase of activity onset relative to lights off (psi) was not affected by 0.6% PTU. In LD 6:18, mean psi was 16.7 h, but this shortened to 13.3 h during PTU, returning to 16.0 h after PTU removal. In intact males under LD 14:10, the three PTU diet concentrations failed to differentially suppress thyroxine and triiodothyronine levels. Food intake and body weight were differentially reduced by the PTU treatments. A 0.5% quinine hydrochloride diet also reduced food intake and body weight but did not change tau. The inconsistency between the dose-tau response and the dose-thyroid hormone response suggest that PTU may affect circadian rhythmicity independent of its action on the thyroid neuroendocrine axis.

Animals↗
PubMed1997

Regulated hypothermia in the hypothyroid rat induced by administration of propylthiouracil.

Propylthiouracil (PTU), an antithyroidal drug that reduces serum L-thyroxine (T4) and 3,5,3'-triiodothyronine (T3), is presumed to lower core temperature (T0) by impairing metabolic thermogenesis. However, it is not understood why PTU-treated animals cannot use behavioral and other thermoeffectors to maintain normal Tc. Male rats were administered PTU in drinking water (0.05 mg/ml) while the following parameters were measured: 1) Tc and motor activity (MA) recorded by radiotelemetry for 24 h at ambient temperatures (Ta) of 10-30 degrees C; 2) selected Ta, MA, and Tc in a temperature gradient; and 3) Tc, MA, and grooming behavior during exposure to heat stress (TH = 34.5 degrees C) for 2 h. PTU reduced serum levels of T4, and T3 by 95 and 60%, respectively. Tc decreased after 3 days of PTU treatment; a 0.5 degree C decrease in Tc persisted throughout the PTU treatment. PTU rats exposed to Ta of 10-30 degrees C maintained a consistent hypothermic Tc during the light phase; however, a deficit in the stability of Tc at night was noted during exposure to 10 degrees C. In the temperature gradient, PTU rats selected warmer Ta, but their Tc was maintained at the same hypothermic levels as observed at fixed Ta values of 15-30 degrees C. Heat stress caused Tc of control rats to increase to 39 degrees C, whereas Tc of the PTU rats was maintained below 38 degrees C. The regulation of Tc at hypothermic levels over a wide range of Ta values and when rats were housed in a temperature gradient indicates that chronic PTU induces a state of regulated hypothermia.

Animals↗
PubMed2000

Effects of propylthiouracil treatment on antioxidant activities in blood of toxic multinodular goiter patients.

Erythrocyte, serum and plasma antioxidant activities and the effects of propylthiouracil (PTU) treatment on these activities were studied in patients with toxic multinodular goiter. The activities of the erythrocyte antioxidant enzymes (glucose-6-phosphate dehydrogenase, catalase, Cu/Zn-superoxide dismutase, selenium (Se)-dependent glutathione peroxidase and glutathione reductase) and the levels of erythrocyte Se, serum ceruloplasmin and plasma malondialdehyde were significantly higher while serum vitamin E, plasma vitamin C and plasma Se were lower in hyperthyroid patients. PTU treatment, not for 1 but for 3 months caused a partial reversal of antioxidant activities to euthyroid levels. It is suggested that alterations in blood antioxidant activities following PTU treatment might be due to the antioxidant and/or antithyroid effect of this drug.

Adult↗
PubMed2006

Effects of propylthiouracil on testicular tissue in undescended testes of newborn rats.

AIM: The most important goal in the treatment of cryptorchidism is to preserve the potential for fertility. This experimental study was performed to investigate the effect of propylthiouracil (PTU) on the undescended testes (UTs) of newborn rats. MATERIALS AND METHODS: The experimental cryptorchidism model in newborn male rats consisted of 4 groups. The groups A (control) and B (PTU) underwent no surgical intervention, whereas in groups C (UT only) and D (treatment) UTs were produced by dissecting and suturing the future right scrotal area. In groups D and B, 0.1% (w/v) PTU was added to the drinking water of mother rats between 2 and 24 days. At the end of the 90th day rat body weights, testicular weights, Johnsen tubular biopsy scores (JTBSs), seminiferous tubule diameters (STDs), testosterone, and thyroid hormone levels were measured. Mann-Whitney U test was used for statistical analysis. RESULTS: Mean testicular weight was similar between groups A, B and D, and statistically lowest in group C. Mean body weight was statistically higher in groups A and C compared with groups B and D. Mean testosterone levels showed no statistical difference between the groups. Mean JTBSs were statistically higher in groups A and B compared with groups C and D. The value in treatment group D was statistically higher compared to group C (p<0.05). Mean STDs were statistically lowest in group C compared to other groups (p<0.05). No difference was found between groups A, B, and D (p>0.05). Both the mean free triiodothyronine and free thyroxine values between groups A and C and between groups B and D were similar. The values in groups A and C were statistically higher than those of groups B and D (p<0.05). CONCLUSION: PTU-induced transient hypothyroidism in the newborn rat UT model shows protective effects on testicular growth parameters.

Animals↗
PubMed1988

An appropriate model for congenital hypothyroidism in the rat induced by neonatal treatment with propylthiouracil and surgical thyroidectomy: studies on learning ability and biochemical parameters.

Hypothyroidism was induced in rats by treatment with propylthiouracil through the mother's milk throughout the suckling period followed by surgical thyroidectomy without use of radioiodine. The growth of these animals was considerably retarded and their light-dark discriminative operant learning ability was also significantly decreased. Replacement therapy with thyroxine to maintain its normal serum concentration was effective for continuing normal growth and development of learning ability. Therefore, these hypothyroid rats are a useful model of congenital hypothyroidism. Biochemical studies showed that the inhibition of cerebral Na,K-ATPase and succinic dehydrogenase activities detected in early postnatal life in these hypothyroid rats was transient and that normal activities of these enzymes were later regained in adult rats. However, the activity of 2',3'-cyclic nucleotide 3'-phosphohydrolase and the brain myelin remained low throughout life unless thyroxine was administered. Though a critical correlation between biochemical parameters and learning ability is still uncertain, these results suggest that the formation of myelin in the neonatal period is at least dependent on thyroid hormone and would play an important role in mental development.

Animals↗
PubMed1991

Effect of propylthiouracil treatment during prenatal and early postnatal development on the neocortex of rat pups.

The effects of a pre- and postnatal hypothyroid environment on the development of the neocortex have been determined. Rats were treated with propylthiouracil (PTU) with or without thyroid hormone supplementation during pregnancy and throughout the early development of the pups. The Cavalieri method was used to provide an estimate of the volume of the neocortex, and a combination of the Cavalieri method and the 'disector' particle-counting method provided an unbiased estimate of the numbers of glia and neurons in the neocortex. In pups from non-treated rats the mean volume of the neocortex increased from 31.3 mm3 at 5 days postnatally to 191.5 mm3 at 20 days and then remained constant to day 48. Similarly, the mean number of glial cells increased from 5.2 x 10(6) at day 5 to 12.0 x 10(6) on day 20 and then remained constant to day 48. The mean number of neurons in the neocortex in the control condition was constant at about 14.6 x 10(6) from day 5 to day 48. PTU treatment during pregnancy and postnatal development significantly decreased the mean volume of the neocortex at all of the stages studied, for example from 31.3 to 23.3 mm3 (p less than 0.001) on day 5 and from 191.5 to 155.0 mm3 (p less than 0.001) on day 20. Supplementation with thyroxine (T4) or tri-iodothyronine partially reversed this at certain stages. For example, the mean volume of the neocortex at 48 days was 197.5 mm3 in control rats, 118.1 mm3 in PTU-treated rats and 169.3 mm3 in PTU-treated rats supplemented with T4. Within the neocortex, the volume of the neuropile was more severely affected than was the volume of the neuron cell bodies.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1982

Propylthiouracil disposition in pregnant and post-partum women.

Propylthiouracil (PTU) disposition was investigated in hyperthyroid women during pregnancy and post partum. The plasma half-life after the first dose averaged 0.66 h and became greater than 1 h with chronic drug therapy. The apparent volume of distribution after the first dose averaged 0.26 liter/kg, similar to nonpregnant hyperthyroid patients. There was a tendency to increased apparent volume of distribution with chronic drug ingestion. Plasma clearance of PTU showed no change related to disease or to pregnancy. Our data suggest that pregnancy does not have a major effect on the pharmacokinetic disposition of PTU in the hyperthyroid mother. Observation of a prolonged plasma half-life for PTU in 1 patient post partum deserves further investigation to determine if this change is associated with clinically significant therapeutic or toxic effects.

Adult↗