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홍소혜,이재언,안성민,신예영,황대연,양승윤,조성근,안범수 한국독성학회 2017 Toxicological Research Vol.33 No.1
Vitamin D3 is a fat-soluble secosteroid responsible for enhancing intestinal absorption of calcium, iron, and other materials. Vitamin D3 deficiency, therefore, can cause health problems such as metabolic diseases, and bone disorder. Female sex hormones including estrogen and progesterone are biosynthesized mainly in the granulosa cells of ovary. In this study, we isolated granulosa cells from porcine ovary and cultured for the experiments. In order to examine the effect of vitamin D3 on the ovarian granulosa cells, the mRNA and protein levels of genes were analyzed by real-time PCR and Western blot assay. The production of estrogen from the granulosa cells was also measured by the ELISA assay. Genes associated with follicle growth were not significantly altered by vitamin D3. However, it increases expression of genes involved in the estrogen-biosynthesis. Further, estrogen concentrations in porcine granulosa cell-cultured media increased in response to vitamin D3. These results showed that vitamin D3 is a powerful regulator of sex steroid hormone production in porcine granulosa cells, suggesting that vitamin D deficiency may result in inappropriate sexual development of industrial animals and eventually economic loss.
내분비장애의심농약 판별을 위한 호르몬수용체 전사활성시험법 확립
홍소혜,양지연,임정현,박수진,신지영,양시영,길근환 한국농약과학회 2023 농약과학회지 Vol.27 No.4
Pesticides have been classified as a major category in the classification of endocrine disruptors. Rural Development Administration “Registration Standards for Pesticides and technical concentrate” announces repeated-dose toxicity tests and reproductive toxicity tests to detect endocrine disruptors through animal testing. However, this test method cannot evaluate complex endocrine mechanisms, and takes a long period of time, so it is not suitable for confirming whether it is an endocrine disruptor. Therefore, in our study, an in vitro test method that provides mechanistic data was established among the test methods to search for endocrine disruptors listed as OECD TG 455 and 458. Before applying this test method to pesticide evaluation, the conditions for the cell stability test and proficiency material suggested in the guideline were established. As a result, the estrogen transcriptional activity test method using human uterine derived cells (hERα-Hela-9903) accurately predicted 8 positive substances and 2 negative substances out of 10 test substances in the agonist assay. In the antagonist assay, 3 positive substances and 7 negative substances were accurately predicted for 10 test substances. The androgen transcription activity test method using human prostate-derived cells (22Rv1/MMTV_GR-KO) accurately predicted 5 positive substances and 3 negative substances out of 8 test substances in the agonist assay and the antagonist assay, 5 positive substances and 4 negative substances were accurately predicted for 9 test substances. Therefore, in this study, we established an alternative animal test method to confirm endocrine mechanism, and we plan to use it to evaluate various pesticides suspected of causing endocrine disruption in the future.
유창우,홍소혜,이진희,정기경,오재호,정자영,권훈정,강종구,양준영 한국식품과학회 2022 Food Science and Biotechnology Vol.31 No.6
Sub-chronic toxicity studies using rats have been conducted for Cynanchum wilfordii (Maxim.) Hemsley (CW) and Cynanchum auriculatum Royle ex Wight (CA). CW water extract didn’t show any adverse effects whereas administering CW powder decreased body weights in complication with decreased food consumptions. In the case of CA water extract, triglyceride and absolute/relative liver weights were elevated and vacuolation was observed in liver. Treated CA powder in male rats increased alanine aminotransferase and aspartate aminotransferase and induced single cell necrosis and multinucleated hepatocyte in liver. As for female rats, increased absolute/relative weights and hypertrophy/vacuolation in adrenal glands and vacuolation in ovaries were observed when administered CA powder. In conclusion, no observed adverse effect level (NOAEL) of CW water extract was over 5000 mg/kg/day, while NOAEL of CW powder was 700 mg/kg/day for female and 150 mg/kg/day for male. In case of CA, NOAEL of water extract was 1500 mg/kg/day for male and 2000 mg/kg/day for female, while NOAEL of powder was 150 mg/kg/day for both gender. To the best of our knowledge, this is the first sub-chronic toxicity study on the adverse effects, target organs and its dose levels of C. wilfordii (Maxim.) Hemsley and C. auriculatum Royle ex Wight following GLP protocols.