• Toxicological Research
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• v.17 no.3
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• pp.203-213
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• 2001

We investigated the toxic effects of propylthiouracil (PTU) In Sprague-Dawley (SD) rats to develop and validate an enhanced Protocol for Test Guideline 407 as OECD Project. Twenty male and female SD rats,7 weeks old, were treated with PTU in corn oil at levels of 0, 0.1, 1 and 10 mg/kg/day for 4 weeks orally. Clinical observation, body weight changes, food uptake, water consumption, urinalysis, estrus cycle and sperm analysis, serum chemist교, autopsy findings and histopathological findings were evaluated in this study. No clinical signs and mortality were observed in the study. The body weights and food uptakes in the group treated with 10 mg/kg/day were reduced from 3 weeks after the initiation of the treatment. The levels of 3,5,3'-triiodothyronine (T3) and thyroxine (T4, 3,5,3',5'-tetraiodothyrosine) were also significantly decreased in the group treated with 10 mg/kg/day. Also, the relative and absolute organ weights of thymuses were decreased. Thyroid glands of rats in the group treated with PTU 10 mg/kg/day were bigger than those of rats in the control group. In the histopathological examination, diffuse hyperplasia and hypertrophy of thyroid follicular cells were observed in all treatment groups, leading to the reduction of lumen size and papillary enfolding of lining epithelium. The degree of lesion was increased in a dose-dependent manner. The results suggested that PTU would cause toxicity in thyroid gland and decrease the levels of T3 and T4 in SD rats. However there were no effects on the other organ including testis and uterus especially in spermatogenesis and estrus cycle. On the basis of the results, enhanced protocol for Test Guideline (TG) 407 may be sensitive and reliable to detect endocrine-active substances like PTU.

• The Journal of Korean Obstetrics and Gynecology
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• v.28 no.3
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• pp.54-73
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• 2015

Objectives The object of this study was to evaluate the effect of Yikgeebohyul-tang aqueous extracts (YKBHT) on the propylthiouracil (PTU)-induced rat hypothyroidism. Methods The rats were divided into 6 groups : intact vehicle control, PTU control, LT4, YKBHT 500, 250 and 125 mg/kg treated groups. Hypothyroidism was induced by daily subcutaneous treatment of PTU 10 mg/kg for 28 days. YKBHT aqueous extracts were administered once a day as an oral dose of 500, 250 and 125 mg/kg for 42 days. The changes were observed : weight of body, thyroid gland, liver, testis, epididymis and prostate, serum thyroid hormone levels, serum male sex hormone levels, serum lipid profiles, liver and testis antioxidant system. These results were compared with LT4 0.5 mg/kg intraperitoneally treated rats. Results These PTU induced hypothyroidism and related hepatic and male reproductive organ damages were favorably and dose-dependently inhibited by treatment of YKBHT 500, 250 and 125 mg/kg, and YKBHT also effectively regulated the PTU-induced abnormal antioxidant defense factor changes in the both liver and testis. Although, LT4 also inhibited PTU-induced hypothyroidism and relative liver damages. But it deteriorated the hypothyroidism related testis, epididymis and prostate damages through testicular oxidative damages. Conclusions : The result of this study suggests that YKBHT has favorable effects on the hypothyroidism and related liver and reproductive organ damages with augmentation of antioxidant defense factor in the testis and liver. YKBHT 500, 250 and 125 mg/kg dose-dependently inhibited PTU-induced hypothyroidism and related liver and male reproductive organ damages in rats.

• Journal of Physiology & Pathology in Korean Medicine
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• v.33 no.2
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• pp.123-130
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• 2019

In this study, we investigated the effects of MOK pharmacopuncture at high-doses which are increased 10 to 100-fold in clinics, on propylthiouracil (PTU)-induced hypothyroidism in rats and the safety. We measured the changes of body weight, food and water intake, body temperature, the serum levels of thyroid hormones (TSH, T3, and T4), AST and ALT, glucose, lipid metabolites (total cholesterol, HDL-cholesterol, LDL-cholesterol, and triglyceride) and observed histopathological changes of thyroid tissues by H&E staining. We also analyzed the peaks of constituents of MOK using HPLC. In the results, the treatment of MOK pharmacopuncture at high-dose (30 mg/kg) in hypothyroidism-induced rats for 2 weeks was shown the improvement effects on the decrease of body weight, food intake, and body temperature, The MOK pharmacopunture at high dose regulated the imbalance of thyroid hormones, glucose, and lipid metabolites and also inhibited the structural damages of thyroid tissues. In liver damage, the MOK pharmacopuncture at high dose reduced the increase of AST and ALT levels in hypothyroid rats. We identified the MOK constituents in HPLC analysis. In conclusion, the treatment of MOK pharmacopuncture at high dose has a therapeutic effect on hypothyroidism without liver toxicity, suggesting that the MOK pharmacopuncture be usefully applicable to treat with hypothyroidism in clinics.

• Medical Lasers
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• v.10 no.1
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• pp.37-44
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• 2021

Background and Objectives Hypothyroidism is the most common endocrine disease. On the other hand, there is no treatment that can improve the thyroid function. Low-level laser therapy (LLLT) can improve the cellular activity. The effect of hypothyroidism is not obvious. This study examined the effects of LLLT on the thyroid gland function of a propylthiouracil (PTU)-induced hypothyroidism mouse model. Materials and Methods Twenty-five male ICR mice were distributed into five groups of five animals each: Negative control (none PTU animal) and positive control (PTU animal) of unirradiated animals, and three experimental groups with LLLT (3J, 6J, and 12J). Each mouse was exposed to a distinct dose of a 632-nm laser once a week for three rounds. The positive control group and three LLLT groups were induced into a hypothyroidism state by PTU administration. The animals' thyroid-stimulating hormone and thyroxine levels were measured using an ELISA kit, and their thyroid tissue was harvested and analyzed after sacrifice at the end of the experiment. The hormone level and morphological changes in the tissue of the five groups were compared. Results The thyroid hormone levels in the control group and LLLT groups were similar. On the other hand, the thyroid tissue of the LLLT groups showed some morphological changes that were similar to those of iodine deficiency thyroid. Conclusion LLLT did not affect the thyroid gland function in PTU-induced hypothyroidism mice.

• Korean Journal of Agricultural Science
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• v.13 no.2
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• pp.210-218
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• 1986

This study was conducted to find out the effects of propylthiouracil and thyroxine on thyroid function and body growth in female rats. One hundred and forty-four female rats (Wistar-imamichi albino rats) of 25 days old were divided into 4 groups; thyroidectomy (Thx), propylthiouracil (PTU), thyroxine (Thyro.)and control (Cont.) groups. Thirty-six rats were allotted to each group, and changes of body weights were weekly checked. In addition, 6 rats in each group were sacrificed at 1, 2, 3, 5 and 6 weeks after treatments with time elapse for investigating changes of thyroid weights and tissues. The results obtained were as follows: 1. The weights of thyroid gland showed significant differences among all the compared groups at all observation times. The weights of thyroid glands in PTU group were higher than those in control group, but those in the Thyro. group were lower than those in control group. 2. In the histological changes of thyroid glands in the PTU group, the follicle epithelium showed columnar cells following hype trophy and hyperplasia from 1 week after treatment. The follicle epithelium in the Thyro. group were recognized inactive showing squamous cells. 3. The body weights showed significant differences among the compared groups from 2 weeks after treatment. The body weights decreased significantly in PTU and Thx. groups, while those in Thyro. group increased significantly in comparison with those in control group. No significant difference in body weight was noted between PTU and Thx. groups.

• The Journal of Korean Obstetrics and Gynecology
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• v.27 no.1
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• pp.41-64
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• 2014

Objectives: This study was to evaluate the effect of Jaeumkanghwa-tang (JEKHT) on the propylthiouracil (PTU)-induced rat hypothyroidism. Methods: Six groups, each of 8 rats per group were used in the present study - intact vehicle control, PTU control, Levothyroxine ($LT_4$), JEKHT 500, 250 and 125 mg/kg treated groups. JEKHT were administered once a day for 42 days as an oral dose of 500, 250 and 125 mg/kg, and hypothyroidism was induced by daily subcutaneous treatment of PTU 10 mg/kg for 28 days. The changes on the body and organ weight, serum hormone and lipid profiles, liver and testis antioxidant defense factors were observed with histopathology of organs. Results were compared with $LT_4$ 0.5 mg/kg intraperitoneally treated rats in this experiment. Results: PTU treatment, marked decrease of body weight, increases of thyroid weight, decreases of liver, testis, epididymis and prostate weights, decreases of serum Tri-iodothyronine ($T_3$), and Thyroxine ($T_4$) level with increase of serum Thyroid-stimulating hormone (TSH) level, decreases of serum testosterone and dihydrotestosterone (DHT) level with increases of serum Follicular stimulating hormone (FSH) level, increases of serum High density lipoprotein (HDL), decrease of triglyceride content, increase of serum Aspartate aminotransferase (AST) level, decreases of liver and testis antioxidant defense factors were observed. In addition, marked hyperplasia of follicular cells with decreases of follicular colloid contents and diameters was additionally demonstrated with the decrease of hepatocyte numbers per unit area due to hypertrophy of hepatocytes related to lipid droplet depositions, increase of a/oligospermatic epididymal tubules with epididymal atrophic changes, seminiferous tubular atrophy with decrease of stage I~II seminiferous tubules in testis, prostate tubular atrophic changes at histopathological inspections. However, these PTU induced hypothyroidism and related hepatic and male reproductive organ damages were favorably and dose-dependently inhibited by treatment of JEKHT 500, 250 and 125 mg/kg, and JEKHT also effectively regulated the PTU-induced abnormal antioxidant defense factor changes in the both liver and testis. Conclusions: JEKHT 500, 250 and 125 mg/kg dose-dependently inhibited PTU-induced hypothyroidism and related liver and male reproductive organ damages in rats.

• Asian-Australasian Journal of Animal Sciences
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• v.12 no.5
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• pp.788-793
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• 1999

To determine the interrelationship between thyroid status and the reparitioning action of clenbuterol (CLE) in broilers, two-week-old female chickens were fed diets containing an antithyroid substance, propylthiouracil (PTU, 0 or 0.3%), CLE (0 to 1 mg/kg), or both for 18 days in a $2{\times}2$ factorial design experiment. Muscle weights (breast muscle, gastrocnemius and peroneus longus) increased only in the normal chickens fed CLE. As absolute mass, protein of leg muscle quantitatively increased in the CLE-fed normal birds. In contrast, inhibition of the CLE-induced protein accretion, especially of peroneus longus, occurred in the PTU group. A quantitative increase in DNA was observed in leg muscles of the normal chickens, but no DNA response to CLE was shown in the PTU-treated chickens. The decreased RNA in leg muscles of the PTU group was more reduced by CLE feeding. Although not statistically significant, the reduced degradation rate of whole muscle protein in normal chickens fed CLE was not confirmed in the PTU-fed group. The present study, therefore, concluded that metabolic action of thyroid hormones was a prerequisite for the hypertrophic effect of ${\beta}$-agonist in broilers.

• Korean Journal of Veterinary Research
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• v.20 no.1
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• pp.17-24
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• 1980

In order to know the effects of thyroid hormone on the bursa of Fabricius in chicken, the bursae were studied with the light microscope after administration of thyroxine(TX) or propylthiouracil(PPT). Macroscopically, the bursa of TY-treated group showed increase in size and thickened folds. while those of the PPT-treated group decrease in size, compared with those of control group. In the light microscopic studies, the bursa of Fabricius of the TX-treated group showed active cell-divisions in the medulla, and increased number of pyroninophilic large lymphocytes and plasma cells containing PAS positive materials in the cytoplasms. On the other hand, the bursa from PPT-treated group revealed decreased number of lymphocytes, significant increase of necrotic lymphocytes in the follicles, and the proliferation of the interfollicular connective tissues. A large number of pyroninophilic lymphocytes and plasma cells were also appeared in the spleen of the TX-treated group.

• The Korean Journal of Pharmacology
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• v.25 no.1
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• pp.13-21
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• 1989

The circadian rhythm of spontaneous motor activity was not significantly altered by $T_4$(4mg/kg, i.p. inj. once a day for 5 days: $T_4$) and PTU (fed ad lib in 0.01% drinking water for 5 weeks: PTU). The plasma thyroxine level was markedly increased by $T_4$ but reduced by PTU, and the plasma thyrotropin level was markedly increased by PTU but moderately increased by $T_4$. Clonidine slightly increased the plasma CS level, but the clonidine effect was significantly enhanced by $T_4-pretreatment$. The brain NE and MHPG contents were little affected by $T_4$ but the NE content was significantly decreased by PTU. The SS-induced increase of plasma CS level was moderately decreased by PTU but increased by $T_4$. However, clonidine significantly inhibited the SS-induced increase, and the inhibitory effect of clonidine was not significantly affected by PTU and $T_4$, respectively. The brain MHPG content and MHPG/NE ratio were significantly decreased by clonidine but increased by SS. The clonidine- and SS-induced changes of brain MHPG content and MHPG/NE ratio were not altered by $T_4$. PTU did not affect the SS-induced increase of brain NE turnover but significantly attenuated the clonidine-induced decrease. The SS-induced increases of brain MHPG content and MHPG/NE rtatio were markedly inhibited by clonidine, and the inhibitory effect of clonidine was not affected by $T_4$ and PTU, respectively. These results suggest that the responses to swim-stress is not signigicantly affected by the alteration of thyroid function and that the hypothalamo-adenohypophysis-adrenocortical stimulation in response to swim-stress seems to be mediated via hypothalamic noradrenergic activation, and the stress response may be inhibited by the agonistic activity of clonidine on the presynaptic ${\alpha}_2-adrenoceptor$.

• Korean Journal of Agricultural Science
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• v.11 no.2
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• pp.252-263
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• 1984

This study was conducted to find out the effect of thyroid function on Hypophysis, and serum FSH and LH concentrations in female rats. One hundred and forty-four female rats (wistar-imamichi albino rats) of 25 days old were divided into 4 groups; thyroidectomy (Thx.) propylthiouracil (PTU), thyroxine (Thyro.) and control (Cont.) groups. Thirty-six heads of rats were arranged to each group. The thyroid glands of the thyroidectomized groups were removed by surgery. The PTU treated groups were drunk the propylthiouracil solution of 0.05% and the thyroxine treated groups were administered subcutaneously with $30{\mu}g$ per 100 g body weight on 3 days intervals. Every 6 heads of rats in each group were sacrificed at 1, 2, 3, 4, 5, and 6 weeks after treatment with time elapse for investigating the weights and histological changes of hypophysis. The results obtained were as follows : 1. The weights of hypophysis at all treated groups were higher than control group, but significantly increased from 3 to 5 weeks. The significance was not recognized between Thyro. and control groups, and Thx. and PTU groups. 2. In the histological changes of hypophysis, eosinophils atrophied from 4 weeks after treatment in Thx. and PTU groups, and basophils showed hypertrophy and hyperplasia from 2 weeks after treatment and thereafter this tendency was more serious showing vacuolization from 4 weeks after treatment. In Thyro. treated group, eosinophils showed slight hypertrophy and basophils atrophied from 5 weeks after treatment but the group showed the similar histological changes in comparison with the control group. 3. The changes of the concentrations of serum FSH at all observation times were significantly recognized among all observation groups. The concentrations in True and PTU groups were significantly lower than those in control group, but those in Thyro. group were significantly higher than those in control group. 4. The changes of the concentrations of serum LH in all treated groups were significantly lower than those in control group. The significance was not recognized between True and PTU group, and Thyro. and control groups.