• 한국환경성돌연변이발암원학회:학술대회논문집
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• 한국환경성돌연변이발암원학회 2002년도 Current Trends in Toxicological Sciences
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• pp.132-132
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• 2002

• Journal of Ginseng Research
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• 제46권4호
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• pp.592-600
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• 2022

Background: Di-(2-ethylhexyl) phthalate (DEHP) is the most common endocrine disrupting chemical used as a plasticizer. DEHP is associated with the development of endometrium-related diseases through the induction of inflammation. The major therapeutic approaches against endometrial cancer and endometriosis involve the suppression of inflammatory response. Korean Red Ginseng (KRG) is a natural product with anti-inflammatory and anti-carcinogenic properties. Thus, the purpose of this study is to investigate the effects of KRG on DEHP-induced inflammatory response in endometrial cancer Ishikawa cells and a mouse model of endometriosis. Methods: RNA-sequencing was performed and analyzed on DEHP-treated Ishikawa cells in the presence and absence of KRG. The effects of KRG on DEHP-induced cyclooxygenase-2 (COX-2) mRNA levels in Ishikawa cells were determined by RT-qPCR. Furthermore, the effects of KRG on the extracellular signal-regulated kinases (ERKs) pathway, COX-2, and nuclear factor-kappa B (NF-kB) p65 after DEHP treatment of Ishikawa cells were evaluated by western blotting. In the mouse model, the severity of endometriosis induced by DEHP and changes in immunohistochemistry were used to assess the protective effect of KRG. Results: According to the RNA-sequencing data, DEHP-induced inflammatory response-related gene expression was downregulated by KRG. Moreover, KRG significantly inhibited DEHP-induced ERK1/2/NF-κB/COX-2 levels in Ishikawa cells. In the mouse model, KRG administration significantly inhibited ectopic endometriosis growth after DEHP-induced endometriosis. Conclusions: Overall, these results suggest that KRG may be a promising lead for the treatment of endometrial cancer and endometriosis via suppression of the inflammatory response.

• 한국수산과학회지
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• 제22권6호
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• pp.424-428
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• 1990

Mulletts, Mugil cephalus were exposed to artificial sea water containing $50{\mu}g/\iota\;of\;^{14}C-la-belled$ di-2-ethylhexyl phthalate(DEHP) during 15 days and returned to the DEHP free sea water in order to know bioconcentration and depuration of DEHP in the fish. Bioaccumulative process of DEHP in the fish was rather fast, and bioconcentration level of $9.7\~14{\mu}g/g$ and a bioconcentration factor of $220\~270$ were reached after one any of exposure. The biological half-life of DEHP in fish was 1.8 days. Five intermediate metabolites of DEHP were detected in the benzene and ethyl acetate fraction of fish by TLC.

• 한국환경성돌연변이발암원학회:학술대회논문집
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• 한국환경성돌연변이발암원학회 2003년도 추계학술대회
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• pp.128-128
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• 2003

• Toxicological Research
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• 제21권3호
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• pp.187-193
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• 2005

The rodent Hershberger assay is considered as a potential short term in vivo screening method for the detection of androgenic or anti-androgenic compounds. The objective of this study was to evaluate the anti-androgenic activities of di(2-ethylhexyl) phthalate (DEHP), di(n-butyl) phthalate (DBP), and butylbenzyl phthalate (BBP). A 10-day Hershberger assay was performed using immature Sprague-Dawley male rats castrated at 6 weeks of age. Tastosterone propionate (TP, 0.4 mg/kg/day) was administered s.c. to castrated male rats and followed by flutamide (1, 5, 10, or 20 mg/kg/day) treatment for 10 days by oral gavage. Similarly, DEHP, DBP, or BBP were also administered by oral gavage at 250, 500, or 1000 mg/kg/day after TP (0.4 mg/kg/day) administration. As expected, flutamide significantly inhibited the TP-induced re-growth of seminal vesicles, ventral prostate, and Levator ani plus bulbocavernosus muscles (LABC) at 1 mg/kg/day and above, and Cowper's glands and glans penis at 5 mg/kg/day and above. DEHP significantly (p<0.05) decreased the seminal vesicles, ventral prostate, LABC and Cowper's glands weights at 1000 mg/kg/day. BBP at 1000 mg/kg/day significantly inhibited TP-induced re-growth of the LABC in the immature castrated male rats, whereas ventral prostate, seminal vesicles, and Cowper's glands weights were unaffected. In contrast to DEHP, DBP did not affect accessory sex organ weights at any concentration. Body weights, combined adrenal glands, and kidney weights were not affected, but liver weights were significantly increased at high dosages in the DEHP, DBP, and BBP treatment groups. Our observations strongly suggest that DEHP acts as an androgen antagonist at the high dose (i.e., 1000 mg/kg/day).

• Toxicological Research
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• 제27권3호
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• pp.185-190
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• 2011

Di-(2-ethylhexyl)-phthalate (DEHP), the most widely utilized industrial plastizer and a ubiquitous environmental contaminant, can act on peroxisome proliferators-activated nuclear hormone receptor family (PPAR) isoforms. To understand the contribution of sphingolipid metabolism to DEHP-induced hepatotoxicity, effect of DEHP exposure on activities of sphingolipid metabolic enzymes in rat liver was investigated. DEHP (250, 500 or 750 mg/kg) was administered to the rats through oral gavage daily for 28 days. The activities of acidic and alkaline ceramidases were slightly increased in 250 mg/kg DEHP-administered rat livers and significantly elevated in 500 mg/kg DEHP-administered ones, although the level of 750 mg/kg DEHP-administered ones was not increased. Neutral ceramidase, acidic and neutral sphingomyelinases, sphingomyeline synthase and ceramide syhthase were not changed at all by DEHP exposure. Therefore, acidic and alkaline ceramidases might play important roles in DEHP-induced hepatotoxicity.

• 분석과학
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• 제15권2호
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• pp.172-179
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• 2002

빗물, 증류수, 정수기 물, 지하수, 수돗물, 시판생수에 포함된 주요 환경호르몬 물질로 알려진 nonylphenol(NP), octylphenol(OP), di(2-ethylhexyl)phthalate(DEHP)를 OASIS 카트리지로 추출한 후 GC/MS를 이용하여 정량하였다. Octylphenol 은 어느 물 시료에서도 검출되지 않았으나, nonylphenol 의 경우는 그 존재량이 빗물<정수기 물<증류수<지하수<수돗물<시판생수의 순으로 증가하였으며, 시판생수의 경우 최고 $0.44{\mu}g/L$(ppb)가 포함되어 있었다. Di(2-ethylhexyl)phthalate는 모든 물 시료에 포함되어 있었으며 빗물의 경우 $1.7{\sim}2.9{\mu}g/L$, 증류수는 $8.7{\sim}31.7{\mu}g/L$, 정수기 물은 $0.6{\sim}5.6{\mu}g/L$(평균: $2.5{\pm}0.3{\mu}g/L$)로 다른 값에 비하여 매우 안정한 값을 나타냈고, 전주근교 지하수는 $1.1{\sim}6.0{\mu}g/L$, 수돗물은 평균 $3.1{\sim}5.7{\mu}g/L$, 시판생수는 $0.5{\sim}67.6{\mu}g/L$ 이였으며 시중의 시판 생수 중 40% 이상이 USEPA기준을 초과하고 있었다.

• Preventive Nutrition and Food Science
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• 제2권2호
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• pp.96-100
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• 1997

Carcinogenicity of di(2-ethylhexyl)phthalate(DEHP) to the mose forestomach and its inhibitor activity for the initiation of Benzo[a]pyrene(BP)-induced mouse forestomach neoplasia were studied on the mouse forestomach carcinogenesis regimen. One hundred female ICR mice(6~7 weeks of age) were hosed in a poly-carbonate cage (4 mice/cage) in a humidity- and temperature-controlled room subjected to a semipurified diet for a week. Mice were divided into 4 treatment groups (25 mice/treatment): Basal diet, DEHP, BP, and BP+DEHP. On Monday and wednesday, 0.1ML DEHP mixed with 0.1ml olive oil (for DEHP and DEHP+BP treatment groups) or 0.1ml saline+0.1ml olive oil (for basal diet group) was intubated, p.o., and on Friday, 2mg BP dissolved in 0.2ml olive oil (for BP and BP+DEHP treatment groups) was intubated, p.o. This cycle was repeated for 4 weeks. Beginning with the first intubation of BP an continuing thereafter, body weight and food intake were recorded once and twice weekly, respectively. All surviving mice were sacrificed 22 weeks after the first dose of BP intubation and countered forestomach tumor. No tumor was formed by DEHP treatment. 5.75 tumors per mouse was formed by BP treatment, whereas its number was reduced to 4.53 by BP+DEHP treatment. Similar results were seen in the tumor incidence. Body weight gain was not affected by DEHP treatment, when compared to that b basal diet treatment. The body weight was significantly reduced by BP treatment, but its reduction was recovered to the level of the basal diet group by BP+DEHP treatment. No significant difference was seen in food intake among all treatment groups. These results indicate that DEHP lacks carcinogenic activity to the mose forestomach and rather inhibits the initiation of BP-induced mose forestomach neoplasia.

• 환경생물
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• 제17권3호
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• pp.285-292
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• 1999

플라스틱 제품의 가소제로 널리 사용되며, 최근 내분비 교란물질로 알려져 있는 di-(2-ethylhexyl)phthalate(DEHP)를 흰쥐에 15일 동안 구강 투여(1g/kg/day, 2g/kg/day, 3g/kg/day)한 후, 정자형성과정에 연관된 정소의 기능과 구조에 미치는 영향을 조사하였다. DEHP 처리군에서는 대조군에 비하여 체중 증가율이 감소하였을 뿐만 아니라 정소의 무게도 감소하였다. 또한 세정관의 직경이 고농도군으로 갈수록 작아지는 경향을 보였으며 세정관내의 세포층이 감소하는 현상이 나타났다. 미세구조의 변화를 관찰한 결과, 실험군은 세정관내 세포사이 공간이 증가하였으며 정원세포와 정모세포의 수가 감소하였고, 세포질내 공포가 증가하는 것이 관찰되었다. 또한 세정관내 Sertoli 세포의 전체 세포질 양이 감소하는 경향을 보였고, 정원세포의 경우 핵막 이중층이 분리되는 현상을 보였다. 특히 고농도군의 세정관내에서는 Sertoli 세포 이외의 세포는 거의 관찰되지 않았으며, 세포사이 공간과 공포들이 상당히 증가하였다. Sertoli 세포의 핵막은 심하게 함입된 형태를 나타냈으며 이질염색질이 증가하여 염색질의 덩어리를 이루고 있었고, Sertoli 세포들을 지지하는 기저판은 심하게 굴곡된 형태를 보였다. Leydig 세포의 미세구조에 있어서도 실험군은 대조군과 비교하여 현저한 차이를 보였다. 세포질내의 활면소포체와 핵막 이중층이 심하게 팽대되는 경향을 보였으며 핵내에 이질염색질이 상당히 증가하고 세포질내 리소솜이 증가하는 특징을 보였다.또한 혈청내 테스토스테론 함량에 있어서도 실험군은 현저히 낮은 수치를 나타냈다. 결론적으로, DEHP는 정소의 발달을 농도의존적으로 저해하고, Leydig 세포의 테스토스테론 합성기능을 저해하며, 이어서 세정관내부의 Sertoli 세포의 구조와 기능을 손상시켜 생식세포들의 괴사를 유도하는 과정을 통해 일련의 정자형성과정을 억제하는 것으로 사료된다.

• Toxicological Research
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• 제26권1호
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• pp.75-82
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• 2010

This study was carried out to investigate the short term toxicity of nine phthalate diesters including di-2(ethylhexyl) phthalate (DEHP), di(n-butyl) phthalate (DBP), di-n-octyl phthalate (DnOP), diethyl phthalate (DEP), butylbenzyl phthalate (BBP), dimethyl phthalate (DMP), di-isodecyl phthalate (DIDP), diundecyl phthalate (DUP), and di-isononyl phthalate (DINP) and five phthalate monoesters including mono- (2-ethylhexyl) phthalate (MEHP), monobutyl phthalate (MBuP), monobenzyl phthalate (MBeP), monoethyl phthalate (MEP), monomethyl phthalate (MMP) and phthalic acid (PA) in Sprague-Dawley male rats. Animals were administered 250 mg/kg/day (monoesters and PA) or 500 mg/kg/day (diesters) of phthalate for two weeks. All animals were examined for body and organ weights, blood hematology, serum biochemistry, and urine analysis. The body weight gain was significantly lower in rats treated with BBP, DBP, DINP, MEHP, MBuP, and PA than that of control. Liver weights were significantly increased in the DEHP, DBP, DnOP, DIDP, and MEHP groups as compared to the control group. Testes weights were significantly decreased only in the DEHP-, DnOP-, and DIDP-treated groups as compared to the control. Significant differences in hematological changes were not observed in any treatment groups. Significant increases in blood glucose levels were observed in the DEHP, MEHP, and MBeP groups. Aspartate aminotransferase (AST) levels were significantly increased in the DBP, DUP, DINP, MBuP, and MBeP groups, whereas alanine aminotransferase (ALT) levels were significantly increased only in the DEHP and MEHP groups. Serum ALP levels were significantly higher in phthalate diester (500 mg/kg/day)-treated rats as compared to control. However, the total cholesterol level was significantly reduced in the DEHP- and DIDP-treated groups, whereas serum triglyceride (TG) levels were higher in the DINP-, MEHP-, and MBuP-treated groups. These results suggest that short term toxicity of phthalate monoesters produces adverse effects as similar to phthalate diesters in Sprague-Dawley rats.