• Toxicological Research
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• 제16권1호
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• pp.33-37
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• 2000

Hershberger assay is known as one of the in vivo-short-term scrrning assays for endocrine disrupting chemicals (EDCs), but this method is not a validated test system. In the present study, the establishment of Hershberger assay to detect EDCs was tried using a model substance, di(n-butyl)phthalate (DBP), a plasticizer for plastics. Thirty-six immature male rats were randomly assigned to six groups: DBP 0, 40, 200, and 1000mg/kg, a positive control (flutamide 20 mg/kg), and a combination group(DBP 1000mg/kg and testosterone 50 ug/kg). DBP and flutamide were administered by gavage to male rats from day 21 to 40 post partum. Testosterone was subcutaneously injected during the same period. We evaluated body weigth gain, weights of ventral prostate, seminal vesicle, and levator ani and bulvocavernous muscle, and serum concentrations of testosterone and lutenizing hormone in male rats. The weights of seminal vesicle and levator ani and bulvocavernous muscle of males receiving 1000mg/kg of DBP was significantly lower than controls. There was no effect of DBP-treatment on body weight gain, prostate weight, and hormone concentrations. In the positive control group, the weights of seminal vesicle and levator ani and bulvocavernous muscle of males receiving 20mg/kg of flutamide were significantly lower than controls. In the combination group, there was no effect of co-treatment of DBP and testosterone on all parameters effect against DBP. This method was found to be a useful short-term screening assay system for EDCs.

• 한국식품과학회지
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• 제31권2호
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• pp.535-539
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• 1999

콩은 항에스트로젠효과와 항암효과를 가지는 것으로 나타나 최근 많은 관심의 대상이 되고 있다. 콩의 전립선암과 유방암 억제 기작으로 항에스트로젠 효과와 항안드로젠 효과가 보고되었지만 다른 조직에서 발현되는 항암활성 특히 화학적으로 유도되는 발암의 억제기작에 대해서는 아직 분명히 밝혀진 바가 없다. 본 연구에서는 콩이 생식기관이외에도 항암활성을 나타내리라 가정하고 그 기작을 규명하고자 하였다. 콩의 메탄올추추출물의 산가수분해물은 생쥐의 폐에서 항암효소계인 quinone reductase의 활성을 유의적으로 증가시켰으며 신장과 소장에서 1상효소계의 지표효소인 arylhydrocarbon hydroxylase효소활성을 억제하는 것으로 나타났다. 따라서 메탄올 추출물에 배당체로 존재하는 화합물이 산처리에 의하여 유리형으로 전환되면서 화학적 발암을 억제하는 활성을 획득하는 것으로 추정된다. 한편 benzo(a)pyrene으로 위암과 폐암을 유발시켰을 때, 콩추출물 첨가 식이는 폐암 발생을 현저히 낮추는 것으로 확인되었다. 이렇듯 화학적발암에 대한 콩 추출물의 방어효과는 약물대사효소계의 조절과 관련이 있는 것으로 추정된다.

• Tuberculosis and Respiratory Diseases
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• 제68권4호
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• pp.226-230
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• 2010

Androgen deprivation therapy, which is the standard treatment for metastatic prostate cancer, includes nonsteroidal antiandrogenic drugs, such as flutamide, nilutamide and bicalutamide. Of them, bicalutamide rarely induces interstitial pneumonia. We report a case of bicalutamide-induced interstitial pneumonia. A 68-year old male diagnosed with prostate cancer and multiple bone metastases presented with dry cough and low grade fever for 3 days. He had taken bicalutamide (50 mg/day) for 13 months. High resolution computed tomography revealed ground glass opacity in his right upper lung. The laboratory studies showed no eosinophilia in the serum and bronchoalveolar lavage fluid. Despite the use of antimicrobial agents for 2 weeks, the extent of the lung lesions increased to the left upper and right lower lung. He had no environmental exposure, collagen vascular disease and microbiological causes. Under the suspicion of bicalutamide-induced interstitial pneumonia, bicalutamide was stopped and prednisolone (1 mg/kg/ day) was initiated. The symptoms and radiologic abnormalities were resolved with residual minimal fibrosis.

• 한방안이비인후피부과학회지
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• 제15권1호
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• pp.315-335
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• 2002

This study was carried out to prove the effects of CBTLC on the $5{\alpha}$-reductase inhibition, the sterilizing power for Propionibactrium acnes, the cytotoxicity of human monocyte, the inhibition for prosta-glandins($PGE_2$), Interleukins(IL-$1{\beta}$) and TNF-${\alpha}$ in inflammation, and the size of Hamster ear sebaceous gland concerned with Acnes. The result were obtained as follows : 1. On the $5{\alpha}$-reductase inhibition of CBTLC in vitro, An undiluted solution of CBTLC was $71{\%}$ inhibition on $5{\alpha}$-reductase and $\frac{1}{10}$ diluted solution of CBTLC was $20{\%}$ inhibition on $5{\alpha}$-reductase. 2. On the sterilizing power for Propionibactrium acnes concerned in Acnes, an undiluted solution and $\frac{1}{10}$ diluted solution of CBTLC formed 12mm clear zone diameters. 3. CBTLC was showed the cytotoxicity of human monocyte in $0.08{\%}$ and $0.12{\%}$ of CBTLC. 4. $0.01{\%}$ and $0.04{\%}$ of CBTLC inhibited the production of prostaglandins($PGE_2$) in the human monocyte stimulated with P. acnes LPS. 5. $0.08{\%}$ and downward of GMHBS inhibited the production of interleukins(lL-$1{\beta}$) in the human monocyte stimulated with P. acnes LPS. 6. $0.08{\%}$ and $0.12{\%}$ of GMHBS inhihited the production of TNF-${\alpha}$ in the human monocyte stimulated with P. acnes LPS. 7. As the antiandrogenic compound, CBTLC was used in hamster ears with topical application. CBTLC was diminished slightly on the size of hamster ears sebaceous gland.

• 대한한의학회지
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• 제26권1호
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• pp.134-147
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• 2005

Objective: This study was carried out to investigate the effects of Gami-Shengmayuipung-tang on acne. Methods : The effects of Gami-Shengmayuipung-tang (SYTSRG) on acne were measured by the $5\alpha-reductase$ inhibition, the sterilizing power for Propionibactrium acnes, the cytotoxicity of human monocyte, the inhibition for prostaglandins$(PGE_2)$, interleukins $(IL-l\beta)$ and $TNF-\alpha$ in inflammation, and the size of the hamtster ear sebaceous gland related to P. acnes. Results: On the $5\alpha-reductase$ inhibition of SYTSRG in vitro, an undiluted solution of SYTSRG showed $80\%$ inhibition on $5\alpha-reductase$ and 1/10 diluted solution of SYTSRG showed $40\%$ inhibition on $5\alpha-reductase$. On the sterilizing power for Propionibactrium acnes related acne, an undiluted solution and 1/10 diluted solution of SYTSRG formed $12\beta{\AE}$ clear zone diameters. SYTSRG did not show cytotoxicity of human monocyte. Concentrations of $0.01\%\;and\;0.04\%\;and\;0.08\%$ of SYTSRG inhibited the production of prostaglandins $(PGE_2)$ in the human monocyte stimulated with P. acnes LPS. $0.08\%$ and less of SYTSRG inhibited the production of interleukins $(IL-l\beta)$ in the human monocyte stimulated with P. acnes LPS. Concentrations of $0.04\%,\;0.08\%\;and\;0.12\%$ of SYTSRG inhibited the production of $TNF-\alpha$ in the human monocyte stimulated with P. acnes LPS. As the antiandrogenic compound, SYTSRG was used in hamster ears with topical application. SYTSRG diminished the size of the hamster ear sebaceous gland in males, but not in females. Conclusion: The present data suggest that SYTSRG may affect the primary stage of inflammation of acne.

• 한국발생생물학회지:발생과생식
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• 제21권4호
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• pp.441-448
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• 2017

Bisphenol-A(BPA) is a member of alkylphenol family, and shows adverse effects including reduced fertility, reproductive tract abnormalities, metabolic disorder, cancer induction, neurotoxicity and immunotoxicity. In the present study, we conducted Hershberger assay to evaluate whether the two candidates to replace BPA have androgenic or antiandrogenic activity. The assay was carried out using immature castrated Sprague-Dawley male rats. After 7 days of the surgery, testosterone propionate (TP, 0.4 mg/kg/day) and test materials (low dose, 40 mg/kg/day; high dose, 400 mg/kg/day) were administered for 10 consecutive days by subcutaneous (s.c.) injection and oral gavage, respectively. Test materials were BPA, isosorbide (ISO) and cyclohexanedimethanol (CHDM). The rats were necropsied, and then the weights of five androgen-dependent tissues [ventral prostate, seminal vesicle, levator ani-bulbocavernosus (LABC) muscle, paired Cowper's glands, and glans penis] and three androgen-insensitive tissues (kidney, spleen and liver) were measured. All test materials including BPA did not exhibit any androgenic activity in the assay. On the contrary, antiandrogen-like activities were found in all test groups, and the order of the intensity was CHDM > BPA > ISO in the five androgen-sensitive tissues. There was no statistical difference between low dose treatment and high dose treatment of BPA group as well as ISO group. In CHDM group, high dose treatment exhibited most severe weight reduction in all measured tissues. There was no statistical difference in androgen-insensitive tissue measurements, except BPA groups. Since the effects of ISO treatment on the accessory sex organs were much less or not present at all when compared to those of BPA, ISO could be a strong candidate to replace BPA. CHDM treatment brought most severe weight reduction in all of androgen-sensitive tissues, so this material should be excluded for further screening of BPA substitute selection.

• 한국발생생물학회지:발생과생식
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• 제22권1호
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• pp.19-27
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• 2018

In the present study, we employed Hershberger assay to determine possible androgenic or antiandrogenic activities of three di-2-ethylhexyl phthalate (DEHP) substitute candidates. The assay was carried out using immature castrated Sprague-Dawley male rats. After 7 days of the surgery, testosterone propionate (TP, 0.4 mg/kg/day) and test materials (low dose, 40 mg/kg/day; high dose, 400 mg/kg/day) were administered for 10 consecutive days by subcutaneous (s.c.) injection and oral gavage, respectively. Test materials were DEHP, 2-ethylhexyl oleate (IOO), 2-ethylhexyl stearate (IOS) and triethyl 2-acetylcitrate (ATEC). The rats were necropsied, and then the weights of five androgen-dependent tissues [ventral prostate, seminal vesicle, coagulating glands, levator ani-bulbocavernosus (LABC) muscle, paired Cowper's glands, and glans penis] and four androgen-insensitive tissues (kidney, adrenal glands, spleen and liver) were measured. All test materials including DEHP did not exhibit any androgenic activity in the assay. On the contrary, antiandrogen-like activities were found in all test groups, and the order of the intensity was ATEC < DEHP < ISO < IOO in the five androgen-sensitive tissues. There was no statistical difference between low dose treatment and high dose treatment of all replacement candidate groups. In DEHP groups, high dose treatment exhibited significant weight gains in LABC and Glan Penis. There was no statistical difference in androgen-insensitive tissue measurements. Since the effects of ATEC treatment on the accessory sex organs were much less or not present at all when compared to those of DEHP, ATEC could be a strong candidate to replace DEHP. IOO treatment brought most severe weight reduction in all of androgen-sensitive tissues, so this material should be excluded for further screening of DEHP substitute selection.

• 환경생물
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• 제27권4호
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• pp.323-333
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• 2009

파라벤은 p-하이드록시 벤조산(p-hydroxybenzoic acid)의 알킬에스테르로, 비교적 빠르게 흡수, 대사 및 배설되는 살균성 보존제로 식품, 화장품, 약품 등에 널리 사용되고 있다. 실제 인체는 파라벤 복합물에 노출된다. 파라벤의 안전성에 관한 연구결과들에 대한 고찰 결과 파라벤 종류에 따라 다양한 독성종말점을 대상으로 파라벤의 급성, 아급성 및 만성독성 영향은 비교적 적은 것으로 나타났다. 파라벤은 에스트로젠 유사활성을 가지며 화장품을 통한 경피흡수를 통해 유방암과의 상관성이 보고되었으나, 이와 상반된 견해도 있다. 파라벤의 항안드로젠성은 남성생식기계의 장애를 유발할 수 있으나 이와 상반된 견해도 있다. 파라벤은 정자의 미토콘드리아 기능 및 남성호르몬 생성을 저해할 수 있으나 이와 상반된 견해도 있다. 배아발달에는 독성이 없는 것으로 나타났다. 세포독성으로는 세포용혈, 미토콘드리아 막투과성 변화, 세포사멸 등을 유발할 수 있다. 수환경에서 파라벤은 환경에스트로젠으로 작동하여 어류에서 내분비장애 효과를 발휘한다. 결론적으로 파라벤은 저독성물질로 분류할 수 있으나, 인체 및 수생동물들에서 파라벤의 노출경로 및 농도, 사용기간 등에 따른 독성과 내분비계장애 효과에 대하여는 다양한 종말점을 대상으로 좀 더 구체적인 독성자료들이 요구된다.

• 한국수정란이식학회:학술대회논문집
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• 한국수정란이식학회 2002년도 국제심포지엄
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• pp.109-109
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• 2002

In recent reports, the multiple reproductive defects such as cryptorchidism, hypospadias, epididymal cysts, low sperm counts, and testicular cancers are increased in humans, and these changes were doubted by the chemicals with estrogenic or antiandrogenic activities in our environment. To compare the effects of neonatal exposure of di (n-butyl) phthalate and flutamide on the development of reproductive organs and to identify the specific mechanisms of these abnormalities related to the male reproducton, Sprague-Dawley neonate male rats were injected subcutaneously during 5-14 days after birth with corn oil (control), flutamide (0.05, 0.1, and 0.5 mg/animal) and DBP (5, 10, and 20 mg/animal). Animals were killed at 31 (immature) and 42 (pubertal) days of age respectively and blood was collected from abdominal aorta for serum testosterone analysis. Testes, epididymides, seminal vesicles, ventral prostate, levator ani plus bulbocavernosus muscle (LABC), cowpers glands and glans penis were weighed. Expression of steroid hormone receptors (AR and ER) was examined in the testes and ventral prostate. At 31 days of age, ventral prostate, seminal vesicles, LABC, and cowpers glands significantly decreased in the flutamide (0.5 mg/animal) and DBP (20 mg/animal), but serum testosterone levels were not changed. Flutamide slightly delayed the testes descent at the high dose (0.5 mg/animal), but DBP did not show any significant effect on the testes descent at all doses. DBP and flutamide decreased the expression of AR protein in the testes but did not affect the expression of ERa and ER protein in the testes. At 42 days of age, ventral prostate, seminal vesicles, and cowpers glands weights were still significantly decreased at the high dose of flutamide (0.5 mg/animal) and DBP (20 mg/animal), but the weights of testes and epididymides were not different. Serum testosterone decreased significantly in DBP treated animals and slightly, not significantly, in flutamide group. While DBP still significantly decreased the expression of AR protein in testis, flutamide recovered from downregulation of AR protein and did not affect the expression of ERa and ER protein in the testes. Based on these results, flutamide and DBP have shown several similar patterns in reproductive abnormalitis, but some marked differences which may be caused by different acting mechanism.