• 제목/요약/키워드: Xenobiotic metabolism

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외인성 화학물질의 대사에 관여하는 Cytochrome P450 (CYP) 효소의 발현조절 기전 (Mechanisms Regulating the Expression of Cytochrome P450 (CYP) Enzymes Involved in Xenobiotic Metabolism)

  • 민계식
    • 생명과학회지
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    • 제34권3호
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    • pp.199-207
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    • 2024
  • CYP 효소는 내인성 및 외인성 화학물질의 대사에 핵심적인 역할을 담당한다. 특히, 약물, 자연생성물 및 환경 독성 화학물질 등은 조직에 따라 특이적 CYP 효소 유전자의 발현을 조절하며, 이는 체내 유입된 약물과 독성물질 등과 같은 화학물질들 사이의 상호작용을 유발하여 이들의 대사에 영향을 줌으로써, 결국 치료 효과와 독성 효과에 변화를 초래한다. 이 분야에 대한 지난 수십 년 동안의 집중적인 연구는, 이러한 CYP 효소 유전자의 발현조절을 매개하는 분자적 기전을 이해하는 데 상당한 진전을 가져왔다. 이제는 구체적인 CYP 효소 유전자의 발현 유도를 조절하는 화합물들뿐만 아니라, 이를 감지하여 특정 CYP 유전자의 발현 조절을 매개하는 데 관여하는 수용체들과 이들의 신호전달 경로들이 비교적 상세히 밝혀졌다. 본 총설에서는, 다양한 화학물질의 노출에 반응하여 CYP 효소 유전자들의 발현 유도를 매개하는 것으로 알려진 주요 외인성 물질-감지 수용체들과 기타 조절인자들의 분자적 작용기전을 요약한다.

Purple Rice Bran Extract Attenuates the Aflatoxin B1-Induced Initiation Stage of Hepatocarcinogenesis by Alteration of Xenobiotic Metabolizing Enzymes

  • Suwannakul, Nattawan;Punvittayagul, Charatda;Jarukamjorn, Kanokwan;Wongpoomchai, Rawiwan
    • Asian Pacific Journal of Cancer Prevention
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    • 제16권8호
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    • pp.3371-3376
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    • 2015
  • Pigmented rice bran has been suggested to be a valuable source of beneficial phytochemicals. We investigated genotoxic and anti-genotoxic effects of purple rice bran extract (PRBE) in rats using a liver micronucleus assay. Purple rice bran was extracted with methanol, obtaining large amounts of phenolic compounds, including anthocyanins and small amounts of gamma-oryzanol. The experimental protocols were divided into two sets. Male rats were divided into three groups. Group 1 was a negative control, while Groups 2 and 3 were fed with 100 and 500 mg/kg bw of PRBE, respectively, for 28 days. PRBE had no effect on micronucleus formation or xenobiotic metabolizing enzymes in rat liver. Experiments concerning the effect of PRBE on $AFB_1$ showed that PRBE significantly lessened the amount of micronucleated hepatocytes in $AFB_1$ treated rats. Furthermore, it modulated metabolic activation of $AFB_1$ metabolism in the liver by suppressing activity and protein expression of CYP1A2, CYP3A and CYP 450 reductase, and enhancing phase II enzymes including GST and UGT. Overall, purple rice bran extract was not genotoxic in rats. It exhibited anti-genotoxicity by modulation some xenobiotic enzymes active in $AFB_1$ metabolism.

양식산과 방류산 조피볼락(Sebastes schlegeli)의 간장 중 해독 및 항산화 효소계의 비교 (Comparison of Xenobiotic Metabolism and Antioxidative Status in Cultivated and Stocked Rockfish Sebastes schlegeli)

  • 이지선;변희국;전중균
    • 한국수산과학회지
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    • 제45권2호
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    • pp.97-103
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    • 2012
  • This study compared the composition and texture of muscle and levels of detoxification and antioxidant enzymes in the livers of stocked and cultivated rockfish Sebastes schlegeli released after the primary culture stage in Tongyoung, South Korea. The crude lipid content of muscle was significantly higher ($P$<0.05) in cultivated rockfish than stocked rockfish, while the texture did not differ significantly ($P$>0.05). The condition factor (CF) and hepatosomatic index (HSI) did not differ significantly and the growth of stocked and cultivated rockfish was similar. The levels of the detoxification enzymes cytochrome P450 (CYP) and Ethoxyresorufin-O-deethylase (EROD) were significantly lower in the livers of stocked rockfish, perhaps because of their reduced exposure to xenobiotic compounds. In addition, stocked rockfish had a significantly ($P$<0.05) lower CAT and higher GR than cultivated rockfish, but similar levels of tGPx, SOD, GSH, and GSSG. The present study shows that the growth rates of stocked and cultivated rockfish are similar and that stocked rockfish are exposed to fewer xenobiotic compounds and less oxidative stress.

Ethnic Differences in the Metabolism of Toluene: Comparisons between Korean and Foreign Workers Exposed to Toluene

  • Kim, Ki-Woong;Won, Young Lim;Ko, Kyung Sun
    • Toxicological Research
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    • 제31권1호
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    • pp.25-32
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    • 2015
  • The objectives of this study were to investigate the individual characteristics, lifestyle habits, exposure levels, and genetic diversity of xenobiotic-metabolizing enzymes involved in toluene metabolism in Korean and foreign workers exposed to toluene at a manufacturing plant. This study was conducted to determine the effects of culture or ethnicity on toluene metabolism. The results showed that blood and urinary toluene concentrations were dependent on the level of exposure to toluene. We analyzed the correlation between toluene metabolism and genetic diversity in glutathione S-transferase (GST) (M1), GSTT1, and cytochrome p-450 (CYP) $2E1^*5$ as well as lifestyle habits (smoking, drinking, and exercise habits). The results revealed significant correlations between toluene metabolism and GSTM1 and GSTT1 genetic diversity, as well as smoking and exercise.

Microbiome-Linked Crosstalk in the Gastrointestinal Exposome towards Host Health and Disease

  • Moon, Yuseok
    • Pediatric Gastroenterology, Hepatology & Nutrition
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    • 제19권4호
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    • pp.221-228
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    • 2016
  • The gastrointestinal exposome represents the integration of all xenobiotic components and host-derived endogenous components affecting the host health, disease progression and ultimately clinical outcomes during the lifespan. The human gut microbiome as a dynamic exposome of commensalism continuously interacts with other exogenous exposome as well as host sentineling components including the immune and neuroendocrine circuit. The composition and diversity of the microbiome are established on the basis of the luminal environment (physical, chemical and biological exposome) and host surveillance at each part of the gastrointestinal lining. Whereas the chemical exposome derived from nutrients and other xenobiotics can influence the dynamics of microbiome community (the stability, diversity, or resilience), the microbiomes reciprocally alter the bioavailability and activities of the chemical exposome in the mucosa. In particular, xenobiotic metabolites by the gut microbial enzymes can be either beneficial or detrimental to the host health although xenobiotics can alter the composition and diversity of the gut microbiome. The integration of the mucosal crosstalk in the exposome determines the fate of microbiome community and host response to the etiologic factors of disease. Therefore, the network between microbiome and other mucosal exposome would provide new insights into the clinical intervention against the mucosal or systemic disorders via regulation of the gut-associated immunological, metabolic, or neuroendocrine system.

Biotransformation of a Fungicide Ethaboxam by Soil Fungus Cunninghamella elegans

  • PARK, MI-KYUNG;KWANG-HYEON LIU;YOONGHO LIM;YOUN-HYUNG LEE;HOR-GIL HUR;JEONG-HAN KIM
    • Journal of Microbiology and Biotechnology
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    • 제13권1호
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    • pp.43-49
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    • 2003
  • Metabolism of a new fungicide ethaboxam by soil fungi was studied. Among the fungi tested, Cunninghamelia elegans produced metabolites from ethaboxam, which were not found in the control experiments. M5, a major metabolite from ethaboxam was firmly identified as N-deethylated ethaboxam by LC/MS/MS and NMR. N-Deethylated ethaboxam has been found as a single metabolite in in vitro metabolism with rat liver microsomes. Ml was proved to be 4-ethyl-2-(ethylamino)-1,3-thiazole-5-carboxamide (ETC) by comparing with the authentic compound. In addition, M2, M3, and M4, and M6 were tentatively Identified by LC/MS/MS as hydroxylated and methoxylated ethaboxams, respectively. Production of the major metabolite, N-deethylated ethaboxam, by the fungus suggested that C. elegans would be an efficient eukaryotic microbial candidate for evaluating xenobiotic-driven mammalian risk assessment.

cDNA Cloning and Expression of a Cytochrome P450 1A (CYP1A) from the Pale Chub, Zacco platypus

  • Jeon, Hyoung-Joo;Park, Young-Chul;Lee, Wan-Ok;Lee, Jong-Ha;Kim, Jin-Hyoung
    • 생태와환경
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    • 제44권4호
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    • pp.364-372
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    • 2011
  • The pale chub (Zacco platypus) is generally found in Asian countries, such as Korea, Japan, and China. Nevertheless, very little information exists about the genes involved in the metabolism of xenobiotics in this species. This species is useful in monitoring the environmental impact on various pollutants in freshwater as a sentinel fish species. We cloned the full-length cDNA sequence of xenobiotic metabolizing cytochrome P450 1A (CYP1A) gene from Z. platypus and characterized it. Tissue distribution and timedependent induction of CYP1A were studied by real-time RT-PCR. Induction pattern of CYP1A was studied by exposing the fish to an arylhydrocarbon receptor agonist, ${\beta}$-naphthoflavone (BNF). The liver showed the highest level of expression in basal state as well as BNF- treated fish. However, appreciable levels of expression were also recorded in Gill and kidney and the least level of expression was observed in the eye. The results of the time-course study revealed an induction in the liver, brain, and gills after 6 h and 12 h in most of the tissues. This study provides an insight into the xenobiotics metabolizing system of Z. platypus and offers baseline information for further research related to biomarker, stress, and adaptive response of this ecologically important fish species in the freshwater environment.