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Effects of Buyang Huanwu Decoction on antioxidant and drug-metabolizing enzymes in rat liver

Chinese Journal of Natural Medicines 2014年第6期12卷 449-454页

作者： FAN Xing-Hua SHI Wei-Zhou CHENG Yun-Xiang YANG Xiu-Fen Department of Pharmacology College of Pharmacy Guangxi University of Chinese Medicine Department of pharmacy Liuzhou Worker's Hospital

AIM: To study the effect of Buyang Huanwu Decoction(BYHWD) on the antioxidant enzymes and drug-metabolizing enzymes in rat liver. METHOD: Following treatment of rats with BYHWD at 6.42, 12.83, or 25.66 g·kg–1 per day for 15 days, microsomes and cytosols isolated from the liver tissues were prepared by differential centrifugation according to standard procedures. The activities of the antioxidant enzymes and cytochrome b5, NADPH-cytochrome P450 reductase, CYP3 A, CYP2E1, UGT, and GST of the rat livers were determined by UV-Vis spectrophotometer. RESULTS: The activities of ALT, AST, antioxidant enzymes, and the Hepatosomatic Index in serum were not significantly affected. In cytosols, the activity of CAT was significantly increased at the dosage of 12.83 g·kg–1, and all the other antioxidant activities and MDA levels were not affected by this treatment. BYHWD had no effect on cytochrome b5, NADPH-cytochrome P450 reductase, CYP3 A, and UGT. At the highest dose(25.66 g·kg–1), the activity of CYP2E1 was significantly inhibited, and the activities of GST and the level of GSH were increased. CONCLUSION: BYHWD is safe for the liver, and has the functions of detoxification and antioxidant. Patients should be cautioned about the herb-drug interaction of BYHWD and CYP2E1 substrates.

关键词： Buyang Huanwu Decoction Antioxidant drug-metabolizing enzymes

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Emerging role of EPHX1 in chemoresistance of acute myeloid leukemia by regulating drug-metabolizing enzymes and apoptotic signaling

Emerging role of EPHX1 in chemoresistance of acute myeloid l...

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第一届中国临床分子诊断大会

作者：程辉第二军医大学附属长海医院

Microsomal epoxide hyrolase 1（EPHX1） is a critical biotransformation enzyme and participants in both the detoxification and activation of potentially genotoxic epoxides.?In this study, we firstly aimed to investigate the?role of?EPHX1 in the chemoresistance of acute myeloid leukemic cells to aclarubicin（ACM） and mitoxantrone（MIT）. EPHX1 m RNA expression and prognosis was measured in acute myeloid leukemia（AML） patients, and the function of EPHX1 in leukemic cell viability and apoptosis induced by ACM and MIT was also measured. Our results found that EPHX1 high expression is obviously associated with recurrence rate, overall survival and time of obtaining first complete remission in AML patients. EPHX1 silencing promoted ACM and MIT induced decrease in cell viability and cell apoptosis of HL-60, K562 and THP-1, which inhibited by EPHX1 overexpression. EPHX1 reduced the susceptibility of leukemic cells to ACM and MIT by regulating drug-metabolizing enzymes（CYP1 A1, GSTM1 and GSTT1） and apoptotic signaling（Bax, Bcl-2 and Caspase-3）. Moreover, Nrf2 overexpression significantly increased EPHX1 expression and leukemic cell viability and decreased leukemic cell apoptosis. Taken together, we summarized the recent findings about the chemoresistance-promoting role of EPHX1, and the potential of EPHX1 was proposed to counteract drug resistance in leukemia treatment.

关键词： EPHX1 acute myeloid leukemia chemoresistance drug-metabolizing enzymes apoptosis

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Impact of obese levels on hepatic expression of drug-metabolizing enzymes in adult and offspring mice

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中国药理学与毒理学杂志 2019年第10期 777-777页

作者： WANG Pei ZHONG Xiao-bo ZHANG Li-rong School of Basic Medical Sciences Zhengzhou University Department of Pharmaceutical Sciences University of Connecticut

OBJECTIVE To investigate the effect of obese levels on the expression of drug-metabolizing enzymes(DMEs) in the liver of adult and offspring *** C57 BL/6 mice(4-5 weeks) were maintained on either a high-fat diet(HFD, 60 kcal% from fat) or low-fat diet(LFD, 10 kcal% from fat). After 4, 8, or 18 weeks of diet treatment, some mice were sacrificed and liver tissues were collected to study the impact of obese levels on the expression of DMEs in adult mice. The remaining mice were mated and offspring of these mice were sacrificed at different ages(day 5-60 after birth) to assess the consequence of parental obese levels on the ontogenic expression of DMEs in the liver of offspring mice. The m RNA expression of nine DMEs(CYP1 A1, 1 A2, 2 B10, 2 C29,2 E1, 3 A11, 3 A16, UGT1 A1, and SULT1 A1) was determined by RT-q PCR. RESULTS Compared with the LFD groups, the m RNA expression of CYP1 A1 was induced in males fed with a HFD for 18 weeks(18-HD) and in females fed with a HFD for 4 or 8 weeks(4-HD and8-HD, respectively). For CYP1 A2 and 2 E1, the m RNA expression was only elevated in the male 4-HD group and in the female 8-HD group. However, consumption with a HFD only induced the expression of CYP2 B10 in males but not in females. Higher m RNA expression of UGT1 A1 was seen in the male 8-HD and 18-HD groups as well as in the female 8-HD group. Concomitantly, the expression of nuclear receptors, including constitutive androstane receptor(CAR), pregnane X-receptor(PXR),hepatocyte nuclear factor(HNF4α), and peroxisome proliferator-activated receptor α(PPARα), aryl hydrocarbon receptor(Ah R) was found to be increased by a HFD in adult mice. For the offspring, family based HFD consumption tended to induce the expression of most DMEs(eg,CYP1 A1, 1 A2, 2 E1, and UGT1 A1) in the offspring derived from 8-HD groups(O-8-HD mice). Altered ontogeny of CYP1 A2 and 2 E1 by HFD was also observed, which changed from an adolescent-enriched pattern to an adultenriched pattern. Whereas, de

关键词： diet-induced obesity overweight high-fat diet drug-metabolizing enzymes

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Recent advance in SNP identifying methods and individualized medication

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Journal of Chinese Pharmaceutical Sciences 2014年第10期23卷 731-738页

作者：彭锐张洪张英武汉大学人民医院药学部

Polymorphisms associated with genes coding for a variety of drug-metabolizing enzymes （DMEs） and associated transport proteins can influence the drug metabolism rate of individuals, potentially affecting the efficacy of drug and the occurrence of adverse reactions. Single nucleotide polymorphisms （SNPs） are prevalent in all types of genetic variations. Reliable SNP genotyping provides excellent markers for detecting genetic polymolphisms, genetic disorders, and resistance of pathogen to drug, which are needed for the genetic diagnosis of disease and subtle genetic factors. With a large number of SNP genotyping studies being conducted, a lot of novel SNP identifying methods have been developed. Several SNP genotyping methods and techniques have been introduced for clinical test. These include TaqMan drug metabolism genotyping assays, pH-sensing semiconductor system, high-resolution melting curve analysis （HRM） of polymerase chain reaction （PCR） amplicons, novel multiplexed electrochemical biosensor with non-fouling surface, DNA hybridization detection using less than 10-nm gap silicon nanogap structure, tetra-primer ARMS-PCR method, acoustic detection of DNA conformation in genetic assays combined with PCR, microbeads-mass spectrometry （MEMS）-based approach, and liquid chromatography-electrospray ionization mass spectrometry. Personalized medicine has changed the conventional ways of using drugs according to experiences. It focuses on making the individualized pattern for each individual based on their own characteristics. Lots of researchers are using the analysis of clinical samples to explain the relationship between the drug adverse reactions and genetic polymorphisms. But it takes a long time from collecting the blood samples for DNA extraction and genotyping to getting results on the side effect of drug through clinical study. Therefore, it is desirable to develop improved in vitro methods to study the drug metabolizing-enzymes and transport protein genetic po

关键词： Single nucleotide polymorphism Genotyping drug-metabolizing enzymes Transporters Pharmacogenomics

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