• Title/Summary/Keyword: CYP model

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Lipid-lowering Effect of Chunggantang in Poloxamer-407 induced Hyperlipidemia Model in Rat (Poloxamer-407로 유발시킨 고지혈증에 대한 청간탕의 효과)

  • Park, Hong-Hak;Cho, Jung-Hyo;Shin, Jang-Woo;Lee, Yeon-Weol;Yoo, Hwa-Seung;Lee, Nam-Heon;Yun, Dam-Hee;Cho, Chong-Kwan;Son, Chang-Gue
    • The Journal of Internal Korean Medicine
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    • v.26 no.4
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    • pp.820-827
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    • 2005
  • 연구목적: 본 연구는 Poloxamer-407로 유발시킨 고지혈증에 대한 청간탕의 효과를 알아보기 위해 수행되어졌다. 실험방법: Poloxamer-407로 쥐에 고지혈증을 유발시킨후 청간탕과 Lipidil을 경구 투여하여 혈청 cholesterol, 고밀도 지단백, 중성지질을 측정하였으며, 지질대사와 관련된 ACAT, DGAT, $CYP7{\alpha}H$, LDL receptor의 gene expression을 RT-PCR를 통해 비교 분석하였다. 실험결과: 청간탕 투여군은 혈청 콜레스테롤을 각각 32% 와 65% (p<0.05)로, 혈청 중성지방을 각각 21% 와 51% (p<0.05)로 감소시켰다. 또한, 청간탕은 LDL 수용체와 $CYP7{\alpha}H$ 유전자 발현을 증가시켰다. 결론: 이상의 연구로부터 우리는 청간탕이 지질의 흡수, 저장을 억제하고 콜레스테롤의 분비를 촉진함으로써 고지혈증에 일정한 효과가 있음을 알 수 있었다.

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Study on the Protective Effect of Corni Fructus against Free Radical Mediated Liver Damage (산수유의 유리자유기에 의한 간손상 보호효과)

  • Ha, Ki-Tae;Kim, Young-Mi;Kim, Cheorl-Ho;Kim, Dong-Wook;Choi, Dall-Yeong;Kim, June-Ki
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.21 no.6
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    • pp.1415-1423
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    • 2007
  • Carbon tetrachloride ($CCl_4$)-induced liver injury depends on a toxic agent that has to be metabolized by the liver NAPDH-cytochrome P450 enzyme system to a highly reactive intermediate. Alternations in the activity of cytochrome P450 enzymes affect the susceptibility to hepatic injury from $CCl_4$. In this study, we evaluated the potential protective activity of the traditional Korean medicinal herb, Corni fructus (CF), against an experimental model of hepatotoxicity induced by $CCl_4$. The CF exhibited a hepatoprotective activity against $CCl_4-induced$ liver damage in Sprague-Dawley (SD) rats, as measured by GOT, GPT, ALP and histological observation. The CF also showed significant decrease of malodialdehyde (MDA) and increase of glutathion (GSH), catalase activity in rat liver homogenate. In addition, the expression of CYP2E1, as measured by reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot analysis, was significantly decreased in the liver of CF treated SD rats. But $CCl_4$ and CF has no significant effect on 1A1 and 3A1 isoform of cytochrome P450. Based on these findings, it is suggested that hepatoprotective effects of CF possibly related to antioxidative effects and regulation of CYP2E1 expression.

Integrative Omics Reveals Metabolic and Transcriptomic Alteration of Nonalcoholic Fatty Liver Disease in Catalase Knockout Mice

  • Na, Jinhyuk;Choi, Soo An;Khan, Adnan;Huh, Joo Young;Piao, Lingjuan;Hwang, Inah;Ha, Hunjoo;Park, Youngja H
    • Biomolecules & Therapeutics
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    • v.27 no.2
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    • pp.134-144
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    • 2019
  • The prevalence of nonalcoholic fatty liver disease (NAFLD) has increased with the incidence of obesity; however, the underlying mechanisms are unknown. In this study, high-resolution metabolomics (HRM) along with transcriptomics were applied on animal models to draw a mechanistic insight of NAFLD. Wild type (WT) and catalase knockout (CKO) mice were fed with normal fat diet (NFD) or high fat diet (HFD) to identify the changes in metabolic and transcriptomic profiles caused by catalase gene deletion in correspondence with HFD. Integrated omics analysis revealed that cholic acid and $3{\beta}$, $7{\alpha}$-dihydroxy-5-cholestenoate along with cyp7b1 gene involved in primary bile acid biosynthesis were strongly affected by HFD. The analysis also showed that CKO significantly changed all-trans-5,6-epoxy-retinoic acid or all-trans-4-hydroxy-retinoic acid and all-trans-4-oxo-retinoic acid along with cyp3a41b gene in retinol metabolism, and ${\alpha}/{\gamma}$-linolenic acid, eicosapentaenoic acid and thromboxane A2 along with ptgs1 and tbxas1 genes in linolenic acid metabolism. Our results suggest that dysregulated primary bile acid biosynthesis may contribute to liver steatohepatitis, while up-regulated retinol metabolism and linolenic acid metabolism may have contributed to oxidative stress and inflammatory phenomena in our NAFLD model created using CKO mice fed with HFD.

Lipid-lowering and Antioxidant Effects of Curcuma Radix in Poloxamer 407-induced Hyperlipidemia Model Rat Models

  • Park, So-Ae;Jo, Hyun-Kyung;Yoo, Ho-Ryong;Kim, Yoon-Sik;Seol, In-Chon;An, Joung-Jo
    • The Journal of Internal Korean Medicine
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    • v.32 no.2
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    • pp.243-258
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    • 2011
  • Objectives : This study investigated the hypolipidemic and antioxidant effects of Curcuma radix using a rat model induced by poloxamer 407 injection. Methods : Serum lipid parameters and oxidative stress-associated biomarkers were determined. Additionally, hepatic cholesterol and triglyceride as well as lipid metabolism-associated gene expressions were observed in hepatic tissue. Results : 1. Curcuma radix ameliorated elevation of serum cholesterol, triglyceride, LDL-cholesterol, MDA, hepatic cholesterol level, and reduction of serum TAC, SOD, GSH, GSH-reductase level. 2. Curcuma radix augmented up-regulated ACAT gene expression. 3. Curcuma radix almost completely ameliorated down-regulated CYP-7A1 but up-regulated HMG-CoA gene expression. Conclusions : The hypolipidemic and antioxidant properties of Curcuma radix were evidenced. This study provides a scientific basis for the clinical application of Curcuma radix and development of hypolipidemics using this herb in the future.

Analysis of Marginal Productivity and Return to Scale Using Estimation of Production Function in Offshore Fisheries (근해어업 생산함수 추정을 이용한 규모수익 및 한계생산성 분석)

  • Sim, Seonghyun;Nam, Jongoh
    • Ocean and Polar Research
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    • v.39 no.4
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    • pp.301-318
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    • 2017
  • The production of Korean offshore fisheries has been gradually decreasing due to the severe depletion of offshore fisheries resources caused by excessive fishing efforts. The production of the offshore fisheries in 2016 was the lowest since 1975. So the federal and local governments in Korea adopted and implemented various fisheries management plans and policies in order to restore fisheries resources. However, these plans and polices have not been successful in re-establishing fisheries resources. Thus, in order to accurately diagnose the situation with regard to offshore fisheries, this study sought to estimate not only the return to scale by fishing gear of offshore fisheries, but marginal productivity of individual fishing gear based on production factors derived from offshore fisheries production functions. The study was organized in the following manner. First of all, this study estimates production functions of offshore fisheries. The Cobb-Douglas and the translog production functions are adopted as offshore fisheries production functions. Specifically, the functions are estimated by crew, vessels, and offshore resource as production factors. The offshore resource is estimated by the Clarke Yoshimoto Pooley model based on the surplus production model. Secondly, the fisheries production functions are extended to the fixed-effect model and the random-effect model with panel data. Thirdly, this study analyzes the return to scale of offshore fisheries and the marginal productivity of the production factors from the estimated offshore fisheries production function. In conclusion, this study suggests plans and countermeasures for productivity improvement by group (labor intensive or technology intensive) based on the characteristics of individual offshore fishing gear.

Experimental Study on the Effects of GamiSamgieum (SGMX) on Hyperlipidemia

  • Kim, Hun;An, Joung-Jo;Jo, Hyun-Kyung;Yoo, Ho-Rhyong;Seol, In-Chan;Kim, Yoon-Sik
    • The Journal of Korean Medicine
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    • v.30 no.3
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    • pp.86-97
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    • 2009
  • Objectives : This study was aimed to investigate the effects of GamiSamgieum (SGMX) on hyperlipidemia using an animal model. Additionally, the underlying mechanisms were investigated by determination of gene expressions related with lipid metabolism. Methods : Forty mice were selected for use in this experiment, and then divided into five groups; Naive, Induced, SGMX 100, SGMX 200, and Lovastatin group as positive control with 8 mice each, and their blood was collected for analysis of blood and serum parameters. Results : Administration of SGMX significantly inhibited the increase of liver weight and the macrovacuolar cytoplasmic alterations in histopathologic finding. SGMX administration significantly protected the liver from pathologic elevation of AST and ALT and from lipid peroxidation. SGMX administration significantly lowered total cholesterol levels and TG, and partially upregulated the gene expression of LCAT, CYP7A1 and LDL-R receptor. Conclusion : SGMX is suggested to possess hypolipidemic effect, and thus could be a potential candidate for herbal hypolipidemic via further studies.

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Protective Effects of YCY against Hepatotoxicity Induced by 2,3,7,8-Tetrachlorodibenzo-p-dioxin(TCDD) in Rats

  • Woon Kwon;Chai, Hee-youl;Young min Cho;Park, Ehn-kyoung;Kim, Ik-soo;Ryu, Kang-sun;Hwang, Seock-Yeon;Yun, Chi-Young;Kang, Jong-Koo
    • Proceedings of the Korean Society of Veterinary Pathology Conference
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    • 2003.10a
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    • pp.46-46
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    • 2003
  • Polychlorinated dibenzo-p-dioxins (PCDDs) are widespread, persistant, and highly toxic environmental pollutants. TCDD is the most potent congener among PCDDs and the most thoroughly investigated model compound of this class of chemicals. These compounds elicit a variety of common biochemical and toxic response, including specific binding to the cytosolic AHR [1] and induces a variety of biological response ranging from induction of cytochrome P-450 1A (CYP1A) to liver damage and cancer [2]. This study was carried out to investigate the protective effects of YCY, extract of a cricket, Gryllus bimaculatus, on hepatotoxicity in 6-week-old SD rat exposured to TCDD (omitted)

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Characteristics of Acetone Enhancement of Microsomal Cytochrome P45O-dependent B(a)P Hydroxylation in 3-Methylcholanthrene-inducible Rat Liver Microsomes

  • Lee, Dong-Wook;Moon, Ja-Young;Lim, Heung-Bin;Sohn, Hyung-Ok;Lee, Young-Gu;Park, Ki-Hyun
    • Journal of the Korean Society of Tobacco Science
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    • v.20 no.2
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    • pp.178-182
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    • 1998
  • Previously, we showed that acetone enhanced aryl hydrocarbon hydroxylase (AHH) activity in only 3-methylcholanthrene (MC)- or $\beta$-naphtoflavone (BNF)-inducible microsomes of rat liver. In the present study, the possible mechanism underlying acetone action on AHH was investigated in the liver microsomes from MC-pretreated rats. Other n-alkylketones except acetone did not increase AHH activity, which rather decreased significantly with the length of alkyl side chain. Acetone had no effect on the activity of NADPH-cytochrome P450 reductase or inhibited the formation of 3-OH benzo(a)pyrene (B(a)P) in nonenzymatic model ascorbic acid system. However, in cumene hydroperoxide (CuOOH)-supported B(a)P hydroxylation, acetone enhanced its velocity remarkably by 30% at the optimal concentration (30 $\mu$M CuOOH and 1.0% acetone). From these results, we conclude that acetone may facilitate the formation of an activated oxygen species or the insertion of oxygen into B(a)P molecule in CYP1A rich microsomes.

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Microarray Analysis of the Gene Expression Profile in Diethylnitrosamine-induced Liver Tumors in Mice

  • Jung Eun-Soo;Park Jung-Duck;Ryu Doug-Young
    • Environmental Mutagens and Carcinogens
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    • v.25 no.4
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    • pp.134-142
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    • 2005
  • Liver cancer is a leading cause of tumor-related mortality, Diethylnitrosamine (DEN) is one of the most extensively studied hepatic carcinogens to date. In this study, the mRNA expression profile in DEN-induced liver tumors in mice was analyzed using DNA microarrays. We report increased expression of genes that participate in hypoxia response, including metallothionein 1 (Mt1), metallothionein 2 (Mt2), fatty acid synthase (Fasn), transferrin (Trf), adipose differentiation-related Protein (AdfP) and ceruloplasmin (CP), as well as those involved in predisposition and development of cancers, such as cytochrome P450 2A5 (Cyp2a5), alpha 2-HS-glycoprotein (Ahsg) and Jun-B oncogene (Junb). The hepatic iron regulatory peptide, hepcidin (Hampl), was downregulated in DEN-stimulated liver tumors. Expression of tumor suppressor genes, such as tripartite motif protein 13 (Trim13), was decreased under these conditions. The data collectively indicate that DEN-induced tumor development can be exploited as a possible model for liver cancer, since this process involves various genes with important functions in hepatic carcinogenesis.

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Metabolites of Latilactobacillus curvatus BYB3 and Indole Activate Aryl Hydrocarbon Receptor to Attenuate Lipopolysaccharide-Induced Intestinal Barrier Dysfunction

  • Wang, Xing;Yong, Cheng Chung;Oh, Sejong
    • Food Science of Animal Resources
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    • v.42 no.6
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    • pp.1046-1060
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    • 2022
  • This study aimed to investigate the effects of the metabolites of Latilactobacillus curvatus BYB3 and indole-activated aryl hydrocarbon receptor (AhR) to increase the tight junction (TJ) proteins in an in vitro model of intestinal inflammation. In a Western blot assay, the metabolites of L. curvatus BYB3 reduced the TJ demage in lipoploysaccharide (LPS) stimulated-Caco-2 cells. This reduction was a result of upregulating the expression of TJ-associated proteins and suppressing the nuclear factor-κB signaling. Immunofluorescence images consistently revealed that LPS disrupted and reduced the expression of TJ proteins, while the metabolites of L. curvatus BYB3 and indole reversed these alterations. The protective effects of L. curvatus BYB3 were observed on the intestinal barrier function when measuring transepithelial electrical resistance. Using high-performance liquid chromatography analysis the metabolites, the indole-3-latic acid and indole-3-acetamide concentrations were found to be 1.73±0.27 mg/L and 0.51±0.39 mg/L, respectively. These findings indicate that the metabolites of L. curvatus BYB3 have increasing mRNA expressions of cytochrome P450 1A1 (CYP1A1) and AhR, and may thus be applicable for therapy of various inflammatory gut diseases as postbiotics.