• Toxicological Research
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• 제17권3호
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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.

• 대한한방부인과학회지
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• 제28권3호
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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.

• 동의생리병리학회지
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• 제33권2호
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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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• 제10권1호
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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.

• 농업과학연구
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• 제13권2호
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• pp.210-218
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• 1986

본(本) 실험(實驗)은 thyroxine 및 propylthiouracil의 투여(投與)에 의(依)한 갑상선(甲狀腺)의 기능변화(機能變化)와 아울러 체성장(體成長)에 미치는 영향(影響)을 구명(究明)코저 실시(實施)하였는 바, 25일령(日齡)의 암 흰쥐를 갑상선척출군(甲狀腺剔出群), propylthiouracil 처리군(處理群), Thyroxine 처리군(處理群) 및 정상대조군(正常對照群)의 사개군(四個群)으로 나누어 배치(配置)하고 각군(各群)을 처리후(處理後) 시간경과(時間經過)에 따라 도살(屠殺)하여 갑상선(甲狀腺)의 중량측정(重量測定) 및 조직학적(組織學的) 검색(檢索)과 아울러 체중(體重)의 변화(變化)를 조사(調査)하였다. 1. 갑상선(甲狀腺)의 중량(重量)은 모든 관찰시간(觀察時間)에서 비교군간(比較群間)에 유의성(有意性)이 인정(認定)되었는데 PTU 처리군(處理群)은 정상대조군(正常對照群)에 비(比)하여 높은 중량(重量)을 나타냈고, Thyroxine 처리군(處理群)은 낮은 값을 나타냈다. 2. 갑상선(甲狀腺)의 조직상(組織像)은 PTU 처리군(處理群)에서는 처리(處理) 1주후(週後)부터 여포상피세포(濾胞上皮細胞)가 증식(增殖) 비대(肥大)를 동반(同伴)하는 원주화현상(圓柱化現象)을 나타내기 시작하여 실험기간(實驗期間)이 경과(經過)될 수록 더욱 진행(進行)되는 조직소견(組織所見)을 보였으며, Thyroxine 처리군(處理群)에서는 여포상피세포(濾胞上皮細胞)가 도평화(屠平化)되는 퇴행성(退行性) 변화(變化)가 인지(認知)되었다. 3. 체중(體重)은 처리(處理) 2주후(週後)부터 비교군간(比較群間)에 유의성(有意性)이 인정(認定)되는 변화(變化)를 보였는데 PTU 처리군(處理群)과 갑상선척출군(甲狀腺剔出群)은 정상대조군(正常對照群)에 비(比)하여 낮은 값을 나타냈고 Thyroxine 처리군(處理群)은 높은 체중치(體重値)를 보였다. 그러나, 다중검정결과(多重檢定結果) PTU 처리군(處理群)과 갑상선척출군(甲狀腺剔出群) 상호간(相互間)에는 유의성(有意性)이 인정(認定)되지 않았다.

• 대한한방부인과학회지
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• 제27권1호
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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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• 제12권5호
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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.

• 대한수의학회지
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• 제20권1호
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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.

• 대한약리학회지
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• 제25권1호
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• pp.13-21
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• 1989

수영-스트레스로 나타나는 뇌 catecholamine대사 및 혈장 corticosterone 함량의 변동에 대한 clonidine(500 ug/kg)의 억제작용을 propylthiouracil(0.01% 용액으로 5주간 마시게함) 및 1-thyrorine(4 mg/kg/day로 5일간 복강내에 주사)로 처치한 웅성-마우스에서 실험관찰하여 다음과 같은 성적을 얻었다. 마우스의 일과성 자발운동량의 변동은 갑상선-홀몬의 변동에 영향을 받지 않았고, 수영스트레스(SS)로 나타나는 혈장 corticosterone(CS)의 증가가 propylthiouracil 전처치 (PTU) 및 1-thyroxine 전처치 (T4)로 각각 다소의 감소 및 증강됨을 보였으나, SS에 의한 혈장 CS증가에 대한 clonidine의 억제작용은 PTU 및 T4의 영향을 받지 않았다. SS부하로 뇌 3-methoxy-4-hydroxyphenylglycol 함량(MHPG)가 유의하게 증가되고 clonidine에 의하여는 MHPG가 현저히 감소되었으나 뇌 norepinephrine 함량(NE)은 별 변동을 보이지 않아서 MHPG/NE비는 SS와 clonidine에 의하여 각각 현저한 증가 및 감소를 나타내었다. 아울러, PTU및 T4은 각각 뇌NE을 유의하게 감소 또는 증가시켰으나 뇌 MHPG에는 별 영향을 미치지 않았다. Clonidine은 SS에 의한 뇌 MHPG 및 MHPG/NE비의 증가를 모두 현저히 억제하였으며 그 억제작용은 PTU 및 T4에 의하여 별 영향을 받지 않았다. 이상의 성적으로 미루어서, 마우스의 일과성 자발운동양상 및 스트레스반응으로 나타나는 혈장 corticosterone의 증가현상등이 갑상선-홀몬의 변동에 별 영향을 받지 않으며, 시상하부-뇌하수체-부신계의 활성화가 시상하부의 norepinephrine성 신경-흥분에 매게되어 나타나는 바, 스트레스성 혈장 corticosterone 증가에 대한 clonidine의 억제작용이 그의 절전-${\alpha}_2-adrenoceptor\;agonist$ 작용에 기인되는 것으로 사료된다.

• 농업과학연구
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• 제11권2호
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• pp.252-263
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• 1984

본(本) 실험(實驗)은 갑상선(甲狀腺)이 하수분(下垂분)의 기능(機能)에 미치는 영향(影響)을 구명(究明)코져 실시(實施)하였는 바, 25일령(日齡)의 암 흰쥐 144마리를 갑상선척출군(甲狀腺剔出群), propylthiouracil (PTU) 처리군(處理群), Thyroxine처리군(處理群) 및 정상대조군(正常對照群)의 4개군(個群)으로 나누어 36마리씩 배치(配置)한 다음 갑상선척출군(甲狀腺剔出群)에서는 갑상선(甲狀腺)을 외과적(外科的)으로 척출(剔出)하였고, PTU처리군(處理群)에서는 음수(飮水)를 0.05%의 propylthiouracil용액(溶液)으로 만들어 자유급수(自由給水)시켰으며, Thyroxine처리군(處理群)에서는 L-thyroxine을 체중(體重) 100g당(當) $30{\mu}g$씩 3일간격(日間隔)으로 주사(注射)하였다. 각(各) 군별(群別)로 처리후(處理後) 시간(時間)의 경과(經過)에 따라 1, 2, 3, 4, 5 및 6주후(週後)에 6마리씩 도살(屠殺)하여 하수체(下垂體)의 중량측정(重量測定) 및 조직학적(組織學的) 검색(儉索)을 실시(實施)하였으며, 아울러 혈청중(血淸中)의 FSH와 LH의 농도(濃度)를 측정(測定)하여 비교검토(比較檢討)하였던 바 그 결과(結果)는 다음과 같다. 1. 하수체(下垂體)의 중량(重量)은 모든 처리군(處理群)이 정상대조군(正常對照群)보다 높은 값을 나타냈는데, 처리(處理) 3주후(週後)부터 5주(週)까지 유의성(有意性)이 인정(認定)되는 변화(變化)를 하였으며 다중검정결과(多重檢定結果) Thyroxine처리군(處理群)과 정상대조군(正常對照群) 및 갑상선척출군(甲狀腺剔出群)과 PTU처리군(處理群) 상호간(相互間)에는 유의성(有意性)이 인정(認定)되지 않았다. 2. 하수체(下垂體)의 조직학적(組織學的) 변화(變化)는 갑상선척출군(甲狀腺剔出群)과 PTU처리군(處理群)에서는 산호성세포(酸好性細胞)가 처리(處理) 4주후(週後)부터 위축(萎縮)되기 시작하였으며 염기호성세포(鹽基好性細胞)는 처리(處理) 2주후(週後)부터 비대(肥大) 증식(增殖)되었는데, 이러한 변화(變化)는 실험기간(實驗期間)이 경과(經過)할수록 더욱 진행(進行)되어서 4주후(週後)부는 공포화(空胞化) 현상(現상)이 인화(認和)되었다. 그러나, Thyroxine처리군(處理群)에서는 처리(處理) 5주후(週後)부터 산호성(酸好性) 세포(細胞)의 근소(僅少)한 비대(肥大)와 염기호성세포(鹽基好性細胞)의 경미(輕微)한 위축현상(萎縮現상)이 발견(發見)되었을 뿐 정상하수체(正常下垂體)에 가까운 조직소견(組織所見)이었다. 3. FSH의 혈청중(血淸中) 농도(濃度) 변화(變化)는 모든 시찰시간(視察時間)에서 비교군간(比較群間)에 유의성(有意性)이 인정(認定)되었는데, 갑상선척출군(甲狀腺剔出群)과 PTU처리군(處理群)은 정상대조군(正常對照群)에 비하여 유의(有意)하게 낮은 값을 나타냈고, Thyroxine 처리군(處理群)은 유의(有意)하게 높은 값을 나타냈다. 4. LH의 혈청중(血淸中) 농도(濃度) 변화(變化)는 모든 처리군(處理群)이 정상대조군(正常對照群)에 비하여 낮은 값을 나타내어 비교군간(比較群間)에 유의성(有意性)이 인정(認定)되었는데, 다중검정결과(多重檢定結果) 갑상선척출군(甲狀腺剔出群)과 PTU처리군(處理群) 및 Thyroxine처리군(處理群)과 정상대조군(正常對照群) 상호간(相互間)에는 유의성(有意性)이 인정(認定)되지 않았다.