• 제목/요약/키워드: CYP model

검색결과 79건 처리시간 0.035초

알코올로 유도된 간 손상 동물모델에서 굴 추출물의 간 보호 효과 (Hepatoprotcetive Effects of Oyster (Crassostrea gigas) Extract in a Rat Model of Alcohol-Induced Oxidative Stress)

  • ;;김범식;이민재;정창식;강남길
    • 한국식품영양과학회지
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    • 제45권6호
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    • pp.805-811
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    • 2016
  • 본 연구는 에탄올로 유도한 알코올성 지방간 동물모델에서 굴 열수 추출물의 알코올성 간 손상 개선 효과를 평가하기 위해 수행되었다. 6주령의 SD rat(male)을 총 6개 군으로 분리하였으며, 양성대조군으로 헛개나무 열매 추출물(500 mg/kg b.w.)을 처리하였다. 6주 동안 하루 간격으로 CGW를 50, 200, 800 mg/kg b.w. 농도로 경구 투여하였으며, control군을 제외한 나머지군은 40% ethanol 5 g/kg b.w.를 6주간 투여하였다. 43일째 실험동물을 희생시켜 혈액 분석 및 간 조직의 항산화 효과 분석을 통해 에탄올로 유도한 동물모델에서 굴 열수 추출물의 알코올성 간 손상 회복 효과를 확인한 결과, 에탄올에 의해 증가한 ALT와 ${\gamma}-GT$의 수준이 CGW를 투여함으로써 유의적으로 감소하였으며, 항산화효소 활성이 증가한 것을 확인할 수 있었다. 에탄올에 의해 손상된 간 조직의 손상 정도를 평가하기 위해 수행한 조직병리학적 검사에서는 에탄올의 투여로 증가한 지방변성 비율 및 간세포 수와 같은 인자들이 굴 열수 추출물의 투여로 유의적으로 회복된 것을 확인하였다. 또한, 에탄올에 의해 증가한 CYP2E1의 발현이 굴 열수 추출물의 투여로 유의적으로 감소하였다. 이러한 연구 결과들로 보았을 때 본 실험에서 굴 추출물의 다당류 및 폴리페놀의 항산화 작용으로 알코올로 유도된 간 손상을 억제할 수 있음을 예상할 수도 있지만, 이후 추가적인 연구로 다른 활성성분의 규명과 관련 활성 기작을 탐구하고자 한다. 본 연구진은 이와 같은 결과를 바탕으로 굴 열수 추출물이 알코올성 지방간 동물모델에서 항산화 방어시스템의 강화를 통해 간 손상을 회복시킴을 확인할 수 있었고, 이러한 연구 성과들로 굴 추출물이 알코올성 간 손상 개선에 있어 효과적인 대안으로서 더욱 더 많은 분야에서 연구되기를 바라는 바이다.

Effect of 6-Hydroxydopamine (6-OHDA) on the Expression of Testicular Steroidogenic Genes in Adult Rats

  • Heo, Hyun-Jin;Ahn, Ryun-Sup;Lee, Sung-Ho
    • 한국발생생물학회지:발생과생식
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    • 제14권3호
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    • pp.199-205
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    • 2010
  • A neurotoxin, 6-hydroxydopamine (6-OHDA) has been widely used to create animal model for Parkinson's disease (PD). The present study was undertaken to examine whether depletion of brain dopamine (DA) stores with 6-OHDA can make alteration in the activities of the testicular steroidogenesis in adult rats. Young adult male rats (3 months old) were received a single dose of 6-OHDA (200 ${\mu}g$ in 10 ${\mu}{\ell}$/animal) by intracerebroventricular (icv) injection, and sacrificed after two weeks. The mRNA levels of steroidogenesis-related enzymes were measured by qRT-PCRs. Serum testosterone levels were measured by radioimmunoassay. Single icv infusion of 6-OHDA significantly decreased the mRNA levels of CYP11A1 (control:6-OHDA group=$1:0.68{\pm}0.14$ AU, p<0.05), CYP17 (control:6-OHDA group=$1:0.72{\pm}0.13$ AU, p<0.05). There were no changes in the mRNA levels of $3{\beta}$-HSD (control:6-OHDA group=$1:0.84{\pm}0.08$ AU) and $17{\beta}$-HSD (control: 6-OHDA group=$1:0.63{\pm}0.20$ AU), though the levels tended to be decreased in the 6-OHDA treated group. Administration of 6-OHDA decreased significantly the mRNA level of StAR when compared to the level of saline-injected control animals (control:6-OHDA group=$1:0.72{\pm}0.08$ AU, p<0.05). Treatment with single dose of 6-OHDA remarkably lowered serum testosterone levels compared to the levels of control group (control:6-OHDA group=$0.72{\pm}0.24:0.13{\pm}0.03ng/m{\ell}$, p<0.05). Taken together with our previous study, the present study demonstrated that the activities of hypothalamus-pituitary-testis hormonal axis could be negatively affected by blockade of brain DA biosynthesis, and suggested the reduced reproductive potential might be resulted in the animals. More precise information on the testicular steroidogenic activities in PD patients and PD-like animals should be required prior to the generalization of the sex steroid hormone therapy to meet the highest standards for safety and efficacy.

Assessment of testicular steroidogenic enzymes expression in experimental animal model following withdrawal of nandrolone decanoate

  • Min, TaeSun;Karthikeyan, Adhimoolam;Lee, Ki-Ho
    • Journal of Animal Science and Technology
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    • 제63권6호
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    • pp.1247-1264
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    • 2021
  • Anabolic steroids are frequently used to increase the growth rate of meat-producing animals. Exposure to an anabolic-androgenic steroid, nandrolone decanoate (ND), is associated with expressional reduction of testicular steroidogenic enzymes. However, the effect of withdrawal of ND exposure on the expression of these testicular molecules has not been thoroughly explored. The current research investigated expression changes of testicular steroidogenic enzymes in rats at several recovery periods (2, 6, and 12 weeks) after the stop of ND treatment with different doses (2 and 10 mg/kg body weight) for 12 weeks. Body and testis weights were recorded, and transcript levels of molecules were determined by quantitative real-time polymerase chain reaction (PCR). The immunohistochemistry was used to examine the changes of immuno-intensities of molecules. At 6 and 12 weeks of the recovery period, the 10 mg/kg ND-treated rats were lighter than other experimental groups. The interstitial compartment vanished by ND treatment filled up as the recovery period became longer. The expression of steroidogenic acute regulatory protein was returned to the control level at 12 weeks of the recovery period. Expression levels of cytochrome P450 side-chain cleavage and 17a-hydroxylase were increased in 2 mg/kg ND-treated group at 6 weeks of the recovery period, and transcript levels of these molecules in 2 and 10 mg/kg ND-treated groups at 12 weeks of the recovery period were significantly lower than the control. Expression levels of 3β-hydroxysteroid dehydrogenase (HSD) type I and 17β-HSD type 3 in 2 mg/kg ND-treated group were comparable with those of control at 12 weeks of the recovery period, but not in 10 mg/kg ND-treated group. Expression of cytochrome P450 aromatase (Cyp19) was reverted to the control level at 2 weeks of the recovery period. Except for Cyp19, there was a visible increase of immuno-staining intensity of other testicular steroidogenic enzymes in the Leydig cells as the recovery period progressed. This research has demonstrated that the cease of ND administration could restore the expression of testicular steroidogenic enzymes close to the normal level. Nevertheless, a relatively long recovery period, compared to the ND-exposure period would be required to retrieve normal expression levels of testicular steroidogenic enzymes.

Fermented ginseng, GBCK25, ameliorates steatosis and inflammation in nonalcoholic steatohepatitis model

  • Choi, Naeun;Kim, Jong Won;Jeong, Hyeneui;Shin, Dong Gue;Seo, Jeong Hun;Kim, Jong Hoon;Lim, Chae Woong;Han, Kang Min;Kim, Bumseok
    • Journal of Ginseng Research
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    • 제43권2호
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    • pp.196-208
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    • 2019
  • Background: Nonalcoholic steatohepatitis (NASH) is one of the chronic inflammatory liver diseases and a leading cause of advanced liver fibrosis, cirrhosis, and hepatocellular carcinoma. The main purpose of this study was to clarify the effects of GBCK25 fermented by Saccharomyces servazzii GB-07 and pectinase, on NASH severity in mice. Methods: Six-wk-old male mice were fed either a normal diet (ND) or a Western diet (WD) for 12 wks to induce NASH. Each group was orally administered with vehicle or GBCK25 once daily at a dose of 10 mg/kg, 20 mg/kg, 100 mg/kg, 200 mg/kg, or 400 mg/kg during that time. The effects of GBCK25 on cellular damage and inflammation were determined by in vitro experiments. Results: Histopathologic analysis and hepatic/serum biochemical levels revealed that WD-fed mice showed severe steatosis and liver injury compared to ND-fed mice. Such lesions were significantly decreased in the livers of WD-fed mice with GBCK25 administration. Consistently, mRNA expression levels of NASH-related inflammatory-, fibrogenic-, and lipid metabolism-related genes were decreased in the livers of WD-fed mice administered with GBCK25 compared to WD-fed mice. Western blot analysis revealed decreased protein levels of cytochrome P450 2E1 (CYP2E1) with concomitantly reduced activation of c-Jun N-terminal kinase (JNK) in the livers of WD-fed mice administered with GBCK25. Also, decreased cellular damage and inflammation were observed in alpha mouse liver 12 (AML12) cells and RAW264.7 cells, respectively. Conclusion: Administration of GBCK25 ameliorates NASH severity through the modulation of CYP2E1 and its associated JNK-mediated cellular damage. GBCK25 could be a potentially effective prophylactic strategy to prevent metabolic diseases including NASH.

만성 알코올 유발 마우스 간손상 및 지방 축적에 대한 제주조릿대잎 에틸 아세테이트 분획물의 간 보호 효과 (Sasa quelpaertensis Nakai ethyl acetate fraction protects the liver against chronic alcohol-induced liver injury and fat accumulation in mice)

  • 김아름;이영주;;김효진;양지원;김주성;지영흔
    • 대한수의학회지
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    • 제60권4호
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    • pp.215-223
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    • 2020
  • Sasa (S.) quelpaertensis Nakai (Korean name, Jeju-Joritdae), which has anti-oxidative and anti-inflammatory activities, is a type of bamboo grass distributed widely in Jeju Island, Korea. S. quelpaertensis leaves are used for therapeutic purposes in traditional Korean medicine. This study examined the hepatoprotective effects of the S. quelpaertensis ethyl acetate fraction (SQEA) in a mouse model to mimic alcoholic liver damage. The mice were administered orally with 30% alcohol (5 g/kg) once per day with or without SQEA treatments (100 and 200 mg/kg) for 14 days consecutively. Alcohol consumption increased the serum alcohol content and histopathological changes but reduced the liver weight. Moreover, the livers of the alcohol group exhibited the accumulation of malondialdehyde and cytochrome P450 2E1 (CYP2E1), and lipid droplet coating protein perilipin-2. On the other hand, SQEA dose-dependently attenuated the alcohol-induced serum ethanol content and liver histopathological changes but increased the liver weight. Moreover, SQEA attenuated the level of CYP2E1 and inhibited alcohol-induced lipogenesis in the liver via decreased perilipin-2 expression. These results suggest that SQEA can provide a potent way to reduce the liver damage caused by alcohol consumption.

Gymnaster koraiensis and its major components, 3,5-di-O-caffeoylquinic acid and gymnasterkoreayne B, reduce oxidative damage induced by tert-butyl hydroperoxide or acetaminophen in HepG2 cells

  • Jho, Eun Hye;Kang, Kyungsu;Oidovsambuu, Sarangerel;Lee, Eun Ha;Jung, Sang Hoon;Shin, Il-Shik;Nho, Chu Won
    • BMB Reports
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    • 제46권10호
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    • pp.513-518
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    • 2013
  • We investigated the protective effects of Gymnaster koraiensis against oxidative stress-induced hepatic cell damage. We used two different cytotoxicity models, i.e., the administration of tert-butyl hydroperoxide (t-BHP) and acetaminophen, in HepG2 cells to evaluate the protective effects of G. koraiensis. The ethyl acetate (EA) fraction of G. koraiensis and its major compound, 3,5-di-O-caffeoylquinic acid (DCQA), exerted protective effects in the t-BHP-induced liver cytotoxicity model. The EA fraction and DCQA ameliorated t-BHP-induced reductions in GSH levels and exhibited free radical scavenging activity. The EA fraction and DCQA also significantly reduced t-BHP-induced DNA damage in HepG2 cells. Furthermore, the hexane fraction of G. koraiensis and its major compound, gymnasterkoreayne B (GKB), exerted strong hepatoprotection in the acetaminophen-induced cytotoxicity model. CYP 3A4 enzyme activity was strongly inhibited by the extract, hexane fraction, and GKB. The hexane fraction and GKB ameliorated acetaminophen-induced reductions in GSH levels and protected against cell death.

Sequential anti-inflammatory and osteogenic effects of a dual drug delivery scaffold loaded with parthenolide and naringin in periodontitis

  • Rui Chen;Mengting Wang;Qiaoling Qi;Yanli Tang;Zhenzhao Guo;Shuai Wu;Qiyan Li
    • Journal of Periodontal and Implant Science
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    • 제53권1호
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    • pp.20-37
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    • 2023
  • Purpose: Our pilot study showed that a 3-dimensional dual drug delivery scaffold (DDDS) loaded with Chinese herbs significantly increased the regenerated bone volume fraction. This study aimed to confirm the synergistic anti-inflammatory and osteogenic preclinical effects of this system. Methods: The targets and pathways of parthenolide and naringin were predicted. Three cell models were used to assess the anti-inflammatory effects of parthenolide and the osteogenic effects of naringin. First, the distance between the cementoenamel junction and alveolar bone crest (CEJ-ABC) and the bone mineral density (BMD) of surgical defects were measured in a rat model of periodontitis with periodontal fenestration defects. Additionally, the mRNA expression levels of matrix metallopeptidase 9 (MMP9) and alkaline phosphatase (ALP) were measured. Furthermore, the number of inflammatory cells and osteoclasts, as well as the protein expression levels of tumor necrosis factor-alpha (TNF-α) and levels of ALP were determined. Results: Target prediction suggested prostaglandin peroxidase synthase (PTGS2) as a potential target of parthenolide, while cytochrome P450 family 19 subfamily A1 (CYP19A1) and taste 2 receptor member 31 (TAS2R31) were potential targets of naringin. Parthenolide mainly targeted inflammation-related pathways, while naringin participated in steroid hormone synthesis and taste transduction. In vitro experiments revealed significant antiinflammatory effects of parthenolide on RAW264.7 cells, and significant osteogenic effects of naringin on bone marrow mesenchymal stem cells and MC3T3-E1 cells. DDDS loaded with parthenolide and naringin decreased the CEJ-ABC distance and increased BMD and ALP levels in a time-dependent manner. Inflammation was significantly alleviated after 14 days of DDDS treatment. Additionally, after 56 days, the DDDS group exhibited the highest BMD and ALP levels. Conclusions: DDDS loaded with parthenolide and naringin in a rat model achieved significant synergistic anti-inflammatory and osteogenic effects, providing powerful preclinical evidence.

떫은감 (Diospyros kaki Thumb.)이 흰쥐의 식이성 이상지질혈증에 미치는 영향 (Inhibitory effects of persimmon (Diospyros kaki Thumb.) against diet-induced hypertriglyceridemia/hypercholesterolemia in rats)

  • 안영숙;;오은경;권오란
    • Journal of Nutrition and Health
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    • 제50권3호
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    • pp.225-235
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    • 2017
  • 본 연구는 성숙도가 다른 떫은감 분말의 이상지질혈증 개선 기능을 확인하기 위하여 Wistar계 흰쥐를 사용하여 시험하였다. 이상지질혈증 유도를 위해 7주간 고지방/고콜레스테롤 식이를 급여하였으며, 미성숙감과 성숙감 건분은 7%, 양성대조군으로 탄닌은 1%의 수준으로 식이에 함께 넣어 같은 기간 동안 제공하였다. 체중의 증가, 혈장과 간 조직의 지질 및 콜레스테롤 수준을 바탕으로 이상지질혈증 모델이 형성되었음을 확인하였다. 탄닌, 성숙감, 미성숙감을 섭취한 경우에는 체중, 혈장 Apo B 및 ox-LDL 수준이 유의적으로 감소하였으며, 특별히 미성숙감은 LDL-C이 감소하는 경향을 나타냈다. 탄닌, 성숙감, 미성숙감의 섭취는 간에서 병리조직학적 손상과 총지질 및 중성지방의 수준을 감소시키는데 유사한 효과를 나타냈다. 그러나 유전자 발현은 서로 다른 양상으로, 탄닌군은 콜레스테롤 합성과 관련된 HMGCR 유전자 발현을 감소시키고, 성숙감은 간에서 담즙산 생성을 통한 콜레스테롤 배출과 관련된 CYP7A1 유전자 발현을 증가시키고, 미성숙감은 지방산 합성과 관련된 FAS 유전자 발현을 억제하는 것으로 나타났다. 이상의 결과로 감은 탄닌 성분을 매개로 콜레스테롤 합성을 억제하고, 성숙도에 따라 미성숙감은 중성지방합성을 억제하고 성숙감은 담즙산 생성을 통한 콜레스테롤 배출을 증가하는 기전으로 콜레스테롤과 중성지질대사 개선을 목적으로 한 기능성 소재로 개발될 가능성이 있는 것으로 판단된다. 향후 변에서 답즙산 분석 등을 통한 기전 확인이 필요할 것이며, 혈중 oxLDL 수준과 같은 항산화 기능과 지질대사 간 상호 영향을 추가적으로 연구해야 할 것으로 사료된다.

다수어업의 갈치 자원평가 및 최적어획량 추정 (Estimation of the Optimal Harvest and Stock Assessment of Hairtail Caught by Multiple Fisheries)

  • 남종오;조훈석
    • Ocean and Polar Research
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    • 제40권4호
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    • pp.237-247
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    • 2018
  • This study aims to estimate optimal harvests, fishing efforts, and stock levels of hairtail harvested by the large pair bottom trawl, the large otter trawl, the large purse seine, the offshore long line, and the offshore angling fisheries by using the surplus production models and the current value Hamiltonian method. Processes of this study are as follows. First of all, this study estimates the standardized fishing efforts regarding the harvesting of the hairtail by the above five fishing gears based on the general linear model developed by Gavaris. Secondly, this study estimates environmental carrying capacity (k), intrinsic growth rate (r), and catchability coefficient (q) by applying the Clarke Yoshimoto Pooley (CY&P) model among various surplus production models. Thirdly, this study estimates the optimal harvests, fishing efforts, and stock levels regarding the hairtail by the current value Hamiltonian method, including the average landing price, the average unit cost, and the social discount rate. Finally, this study attempts a sensitivity analysis to figure out changes in optimal harvests, fishing efforts, and stock levels due to changes in the average landing price and the average unit cost. As results induced by the current value Hamiltonian method, the optimal harvests, fishing efforts, and stock levels regarding the hairtail caught by several fishing gears were estimated as 33,133 tons, 901,080 horse power, and 79,877 tons, respectively. In addition, from the results of the sensitivity analysis, first of all, if the average landing price of the hairtail constantly increases, the optimal harvests of it increase at a decreasing rate, and then harvests finally slightly decrease as a result of decreases in stock levels. Secondly, if the average unit cost of fishing efforts continuously increases, the optimal fishing efforts decreases, but optimal stock levels increase. Optimal harvests start climbing and then decrease continuously due to increases in the average unit cost. In summary, this study suggests that the optimal harvests (33,133 tons) were larger than actual harvests (25,133 tons), but the optimal fishing efforts (901,080 horse power) were much less than estimated standardized fishing efforts (1,277,284 horse power), corresponding to the average of the recent three years (2014-2016). This result implies that the hairtail has been inefficiently harvested and recently overfished due to excessive fishing efforts. Efficient management and conservation policies on stock levels need to be urgently implemented. Some appropriate strategies would be to include the hairtail in the Korean TAC species or to extend the closed fishing season for this species.

황기맥문동탕이 에스트로겐 결핍 Rat의 체중 변화와 비만 관련 유전자 발현에 미치는 영향 (Effects of Hwanggimacmundong-tang on Body Weight and Gene Expression in Obese Rats with Estrogen Deficiency)

  • 이혜인;유동열;유정은
    • 대한한방부인과학회지
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    • 제31권2호
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    • pp.49-67
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    • 2018
  • Objectives: This study was conducted to assess the effects of Hwanggimacmundong-tang extract (HM) on obese rats with estrogen deficiency. Methods: The experiments were performed with ovariectomized rats as estrogen-deficient obesity model. Rats were grouped NC (Normal Control Group; sham operation group), OC (Obesity Control Group; estrogen-deficient group), HML (20 mg/kg/day), HMH (100 mg/kg/day). HM was administered orally for six weeks. Body weights and serum lipid level were measured, and real-time PCR was performed to estimate the effect of HM on gene expression in liver. Results: HM decreased the total cholesterol and triglyceride in serum. And HM increased leptin, CPT1 gene expression in liver tissue of obese rats with estrogen deficiency. However HM decreased $PPAR{\gamma}$, $PGC-1{\alpha}$, HMGCR, CYP8B1, LPL, ACAT1, ACAT2, ApoB, ACOX gene expression in liver tissue of obese rats with estrogen deficiency. Conclusions: It is concluded that HM reduced total cholesterol and triglyceride in serum, and regulate gene expression related to lipid metabolism. These results indicate Hwanggimacmundong-tang that might have potential for treatment of obesity and complications during the menopause caused by estrogen-deficiency.