• Korean Journal of Pharmacognosy
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• v.34 no.1 s.132
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• pp.86-90
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• 2003

For the determination of inhibiting cytochrome P450(CYP)3A4 activity, an improvement HPLC method was established by using a new internal standard and solvent system. Moreover, CYP3A4 amount for a optimum reaction of enzyme was determined by a comparative study with a variety concentration of enzyme. Using a established method, inhibitory effect of CYP3A4 that is drug metabolizing enzyme Investigated on EtOAc extracts of 5-class spices. As a result of experiment, EtOAc extract of white pepper (Piper nigrum L.) showed strong inhibitory activity. On a continuous experiment, the fraction 2, 4 and 5 of while pepper extract showed remarkable inhibitory activity. Pipeline, a main constituent of pepper was not included in these fraction. It is suggested that major compounds for the inhibitory activity of white pepper may be other ingredient that is not piperine.

• Journal of Preventive Medicine and Public Health
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• v.55 no.3
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• pp.280-288
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• 2022

Objectives: One of the most widely used pesticides today is chlorpyrifos (CPF). Cytochrome P450 (CYP)2B6, the most prominent catalyst in CPF bioactivation, is highly polymorphic. The objective of our study was to evaluate the role of CYP2B6^*6, which contains both 516G>T and 785A>G polymorphisms, in CPF toxicity, as represented by the concentration of 3,5,6-trichloro-2-pyridinol (TCPy), among vegetable farmers in Central Java, Indonesia, where CPF has been commonly used. Methods: A cross-sectional study was conducted among 132 vegetable farmers. Individual socio-demographic and occupational characteristics, as determinants of TCPy levels, were obtained using a structured interviewer-administered questionnaire and subsequently used to estimate the cumulative exposure level (CEL). TCPy levels were detected with liquid chromatography-mass spectrometry. CYP2B6^*6 gene polymorphisms were analyzed using a TaqMan^® SNP Genotyping Assay and Sanger sequencing. Linear regression analysis was performed to analyze the association between TCPy, as a biomarker of CPF exposure, and its determinants. Results: The prevalence of CYP2B6^*6 polymorphisms was 31% for ^*1/^*1, 51% for ^*1/^*6, and 18% for ^*6/^*6. TCPy concentrations were higher among participants with CYP2B6^*1/^*1 than among those with ^*1/^*6 or ^*6/^*6 genotypes. CYP2B6^*6 gene polymorphisms, smoking, CEL, body mass index, and spraying time were retained in the final linear regression model as determinants of TCPy. Conclusions: The results suggest that CYP2B6^*6 gene polymorphisms may play an important role in influencing susceptibility to CPF exposure. CYP2B6^*6 gene polymorphisms together with CEL, smoking habits, body mass index, and spraying time were the determinants of urinary TCPy concentrations, as a biomarker of CPF toxicity.

• Proceedings of the PSK Conference
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• 2003.10a
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• pp.88-88
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• 2003

The syntheses of different types of stilbenoid libraries have been studied recently. In these courses, the screening of the generated natural product-mimic focused libraries led to the identification of the novel lead compounds for human cytochrome P450 (CYP) lAs, melanin production, and sortase A. A library of trans-stilbene derivatives was prepared through a new efficient solution pahse synthetic pathway and their inhibitory activities were evaluated on human cytochrome P450s(CYP) 1A1, 1A2, and 1B1 to find a potent and selective CYP1 inhibitor. (omitted)

• Korean Journal of Fisheries and Aquatic Sciences
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• v.35 no.2
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• pp.179-184
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• 2002

Induction of cytochrome P45O (CYP) and 7-etholqresorufin-O-deethylase (EROD) in the microsome exposed to 3-methylcholan-throne (MC), $\beta$-naphthoflavone (BNF) and phenobarbital-Na (PB) was investigated, Microsome was isolated from digestive gland of clam (Coelomactra antiquata) and then exposed to each chemical in concentration range of 0.1 to 1.0 mM for 7 hours. The CYP content and EROD activity in the microsome exposed to each chemical significantly increased compared to the control group. The overall CYP and EROD induction potency was in order of MC>BNF>PB. The induction response of EROD was two times higher than that of CYP level in the microsome exposed to MC, but the induction response of EROD was slightly higher than that of CYP level in BNF and PB exposure groups.

• Childhood Kidney Diseases
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• v.26 no.1
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• pp.63-67
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• 2022

Nephrocalcinosis often occurs in infants and is caused by excessive calcium or vitamin D supplementation, neonatal primary hyperparathyroidism, and genetic disorders. Idiopathic infantile hypercalcemia (IIH), a rare cause of nephrocalcinosis, results from genetic defects in CYP24A1 or SLC34A1. Mutations in CYP24A1, which encodes 25-hydroxyvitamin D 24-hydroxylase, disrupt active vitamin D degradation. IIH clinically manifests as failure to thrive and hypercalcemia within the first year of life and usually remits spontaneously. Herein, we present a case of IIH wih CYP24A1 mutations. An 11-month-old girl visited our hospital with incidental hypercalcemia. She showed failure to thrive, and her oral intake had decreased over time since the age of 6 months. Her initial serum parathyroid hormone level was low, 25-OH vitamin D and 1,25(OH)₂ vitamin D levels were normal, and renal ultrasonography showed bilateral nephrocalcinosis. Whole-exome sequencing revealed compound heterozygous variants in CYP24A1 (NM_000782.4:c.376C>T [p.Pro126Ser] and c.1310C>A [p.Pro437His]). Although her hypercalcemia and poor oral intake spontaneously resolved in approximately 8 months, we suggested that her nephrocalcinosis and renal function be regularly checked in consideration of potential asymptomatic renal damage. Hypercalcemia caused by IIH should be suspected in infants with severe nephrocalcinosis, especially when presenting with failure to thrive.

• Proceedings of the Korean Society of Toxicology Conference
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• 2002.11b
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• pp.149-150
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• 2002

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is the most potent halogenated aromatic hydrocarbon congener that induces expression of several genes including CYP1A. Exposure to TCDD results in many toxic actions such as carcinogenesis, hepatotoxicity, immune suppression, reproductive toxicity and developmental toxicity.(omitted)

• Archives of Pharmacal Research
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• v.27 no.2
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• pp.239-245
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• 2004

KR-31543, (2S,3R,4S)-6-amino-4-[N-(4-chlorophenyl)-N-(2 -methyl-2H-tetrazol-5-ylmethyl) amino]-3,4-dihydro-2-dimethoxymethyl-3-hydroxy-2-methyl-2H-1-benzopyran, is a new neuroprotective agent for preventing ischemia-reperfusion damage. This study was performed to identify the metabolic pathway of KR-31543 in human liver microsomes and to characterize cytochrome P450 (CYP) enzymes that are involved in the metabolism of KR-31543. Human liver microsomal incubation of KR-31543 in the presence of NADPH resulted in the formation of two metabolites, M1 and M2. M1 was identified as N-(4-chlorophenyl)-N-(2-methyl-2H-tetrazol-5-ylmethyl)amine on the basis of LC/MS/MS analysis with a synthesized authentic standard, and M2 was suggested to be hydroxy-KR-31543. Correlation analysis between the known CYP enzyme activities and the rates of the formation of M 1 and M2 in the 12 human liver microsomes have showed significant correlations with testosterone 6$\beta$-hydroxylase activity (a marker of CYP3A4). Ketoconazole, a selective inhibitor of CYP3A4, and anti-CYP3A4 monoclonal antibodies potently inhibited both N-hydrolysis and hydroxylation of KR-31543 in human liver microsomes. These results provide evidence that CYP3A4 is the major isozyme responsible for the metabolism of KR-31543 to M1 and M2.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.28 no.5
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• pp.364-371
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• 2002

Many chemical compopunds are converted into reactive electrophilic metabolites by the oxidative(Phase I) enzymes, which are mainly cytochrome P-450 enzyme(CYPs). Phase II conjugating enzymes, such as glutathione S-transferase(GST), usually act as inactivation of enzymes. Genetic polymorphisms have been found to be associated with increased susceptibility to cancer of the lung, bladder, breast and colorectal. Many of the polymorphic genes of carcinogen metabolism show considerably different type of cancer among different ethnic groups as well as individuals within the same group. The aim of this study is (1) to establish the frequencies of genetic polymorphisms of GSTM1 and CYP1A1 in Korean oral squamous cell carcinoma(SCC), (2) to associate oral SCC with the risk of these genetic polymorphisms. The genetic polymorphisms of the GSTM1 and the CYP1A1 genes among 50 Korean oral SCC were analyzed using polymerase chain reaction(PCR). The results suggest that the homozygote and the mutant type of CYP1A1 MspI polymorphisms may be associated with genetic susceptibility to oral SCC in Korean. A combination of the GSTM1 null type with the homozygote(m1/m1), and the mutant(m2/m2) type of CYP1A1 MspI polymorphisms showed a relatively high risk of oral SCC in Korean. In the smoking group, the GSTM1 wild genotype may be the high risk factor of oral SCC in Korean. These data coincide with the hypothesis which states that different susceptibility to cancer of genetic polymorphisms exist among different ethnic group and different types of human cancer.

• Bulletin of Food Technology
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• v.12 no.2
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• pp.26-38
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• 1999

조리가공 중 생성되는 주요 발암성 이환방향족아민(heterocyclic aromatic amine)인 Trp-P-1 및 Trp-P-2가 human 및 rat keratinocytes에 대해 나타내는 세포 독성을 colony expansion법의 의해 조사, 비교하였다. 특히 Trp-P-2는 human keratinocytes에 대해서는 독성을 나타내지 않은데 반해 rat keratinocytes(계대수 2-5)에 대해서는 독성을 나타내는 선택성을 나타내었다. 이러한 Trp-P-2의 종(species)간 독성감수성 차이가 대사 효소계 활성이나 mutagenic activation상의 차이에 기인되는지를 살펴본 결과, CYP4501As 및 독성감수성 차이가 크게 나타났던 human 및 rat keratinocytes의 microsome에서 거의 같았다. 이와 같은 결과는 CYP4501A1 및 CYP1B1의 mRNA의 발현정도를 northernblot에 의해 살펴보았던 결과에서도 일치하였다. 반면 Trp-P-2의 대사활성화 및 해독화에 관여하는 효소인 N.O-acetyltransferase(NAT)활성은 rat keratinocytes보다 human keratinocytes에서 높았다. 일반적으로 독성물질의 해독화에 관여하는 glutathione S-transferase(GST) 또한 rat keratinocytes보다 human keratinocytes에서 높게 나타났다. Trp-P-2가 mutagenic metabolite로 활성화되는 정도를 salmonella microsome microsuspension assay로 살펴본 결과, 독성 감수성 차이가 크게 나타났던 human 및 rat keratinocytes간의 활성은 비슷한 것으로 나타났다. DNA 및 단백질 adduct형성능의 경우, human 및 rat keratinocytes간 DNA adduct형성능에는 차이가 없었고, 단백질 adduct형성능의 경우만 Trp-P-2에 대한 독성감수성 정도가 컸던 rat keratinocytes가 다른 세포들에 비해 크게 나타났다. 이상의 결과를 종합해 볼 때, CYP1A- 또는 CYP1B1-관련 마이크로솜 효소활성이나 mutagenic activation은 human 및 rat keratinocytes간에 나타났던 독성 감수성의 차이를 설명할 수 없으며, 해독화에 관여하는 효소활성이 종간 관찰되었던 독성 감수성의 차이에 더 중요한 역할을 하는 것으로 보인다.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6507-6512
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• 2013

The purpose of this study was to evaluate the associations of CYP1A1 genetic polymorphisms with the risk of developing esophageal cancer (EC). A case-control study was carried out in a Chinese population in which 157 hospital based EC cases and 157 population based healthy controls with 1:1 match by age and sex were included. PCR based restriction fragment length polymorphisms (PCR-RFLP) were used to detect genotypes in case and control groups. For the CYP1A1 Ile/Val polymorphism, comparing with wild genotype Ile/Ile, both the heterozygote genotype Ile/Val and the combined variant genotype Ile/Val+Val/Val increased the risk of esophageal cancer (OR: 2.05, 95%CI: 1.19-3.54, OR: 1.86, 95%CI: 1.11-3.12). No significant association was found between the CYP1A1 MspI polymorphism and EC. According to analysis of combined genotypes, the TC/AG combined genotype which contained both variant alleles of these two polymorphisms increased the risk of developing EC (OR: 2.12, 95%CI: 1.16-3.85). Our results suggested that genetic polymorphisms of CYP1A1 may increase the susceptibility to EC.