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1.
Rev. Bras. Saúde Mater. Infant. (Online) ; 20(2): 467-471, Apr.-June 2020. tab
Article in English | LILACS, SES-SP | ID: biblio-1136441

ABSTRACT

Abstract Objectives: the present study aimed to evaluate the association between the rs1799998 polymorphism of the CYP11B2 gene and the susceptibility to preeclampsia (PE) in a Brazilian population. Methods: the study group comprised 61 women who were diagnosed with PE. The control group included 116 women who did not show changes in their blood pressure levels during their pregnancies. The rs1799998 polymorphism of the CYP11B2 gene was amplified by allele-specific polymerase chain reaction (PCR). A multiple logistic regression analysis was performed using the SNPStat program to evaluate the risk of the CYP11B2 gene rs1799998 polymorphism contributing to PE. Results: the PE group had the following genotypes: 1.64% CC, 91.80% CT, and 6.56% TT. In the control group, the observed genotypic frequencies were: 11% CC, 73% CT, and 16% TT. The genotypic frequency distribution did not fit the Hardy Weinberg Equilibrium (HWE) in either study group. The multiple logistic regression analysis showed a statistically significant difference for the rs1799998 polymorphism in the recessive model. Conclusion: the results suggest an association between the recessive model of C/C genotype of the rs1799998 polymorphism of the CYP11B2 gene and susceptibility to PE.


Resumo Objetivos: avaliar a associação entre o polimorfismo rs1799998 do gene CYP11B2 e a suscetibilidade à PE em uma população brasileira. Métodos: participaram desse estudo 61 mulheres com PE e 116 mulheres normotensas. O polimorfismo rs1799998 do gene CYP11B2 foi amplificado por PCR alelo-específica. O risco do polimorfismo rs1799998 do gene CYP11B2 contribuir com a PE foi avaliado pela análise de regressão logística múltipla. Resultados: as frequências genotípicas observadas foram 1.64% CC, 91.80% CT e 6.56% TT no grupo PE e 11%CC, 73%CT e 16%TT grupo controle. A distribuição da frequência genotípica não estava em Equilíbrio de Hardy Weinberg em nenhum dos grupos estudados. A análise de regressão logística múltipla demonstrou diferença estatisticamente significativa para o polimorfismo rs1799998 no modelo recessivo. Conclusão: o presente trabalho sugere associação do genótipo C/C no modelo recessivo, do polimorfismo rs1799998 do gene CYP11B2 com a suscetibilidade a PE.


Subject(s)
Humans , Female , Pregnancy , Polymorphism, Genetic , Pre-Eclampsia/genetics , Cytochrome P-450 CYP11B2 , Cytochrome P-450 Enzyme System , Brazil , Genetic Markers , Logistic Models , Genetic Predisposition to Disease , Genetic Profile
2.
Article in Chinese | WPRIM | ID: wpr-828429

ABSTRACT

In this study, based on the transcriptome database of suspension cells of Arnebia euchroma, we explored two candidate cytochrome P450 enzyme genes that might relate to the shikonin biosynthesis downstream pathway when CYP76B74 sequence was referenced. We constructed interference-type hairy roots of candidate genes and cultured them. We measured the fresh weight, dry weight, total naphthoquinone content, shikonin and its derivatives content and expression levels of key enzyme genes involved in shikonin biosynthesis pathway. The effects of candidate genes on the growth and shikonin production of A. euchroma hairy roots were discussed, and the possible regulatory mechanisms that candidate genes affected shikonin synthesis were discussed. Through local Blast and phylogenetic analysis, two candidate CYP450 genes(CYP76B75 and CYP76B100) with high homology to CYP76B74 in A. euchroma were screened, and corresponding interference hairy roots were constructed. Compared with the control(RNAi-control), the fresh weight of CYP76B75 interfered hairy root(RNAi-CYP76B75) and CYP76B100 interfered hairy root(RNAi-CYP76B100) were significantly reduced, while dry weight were not affected, so the dry rate increased significantly. Except for β-acetoxyisovalerylalkannin, which is high in three groups of hairy roots, the contents of shikonin, deoxyshikonin, acetylshikonin, β,β'-dimethacrylicalkannin, β-hydroxyisovalerylshikonin,β-hydroxyisovalerylshikonin, isobutyrylshikonin and total naphthoquinones showed a consistent pattern: RNAi-CYP76B75>RNAi-CYP76B100>RNAi-control. Among them, the synthesis of β-hydroxyisovalerylshikonin was most significantly promoted by interfering with the expression of CYP76B75. The content of β-hydroxyisovalerylshikonin in RNAi-CYP76B75 was 11.7 times that of RNAi-control. RESULTS:: of real-time qPCR analysis showed that compared to RNAi-control, the expression levels of AePGT gene in RNAi-CYP76B75 and RNAi-CYP76B100 were not changed significantly, and the expression levels of CYP76B74 and AeHMGR were up-regulated. In addition, the expression level of CYP76B100 in RNAi-CYP76B75 was down-regulated, whereas in RNAi-CYP76B100, the expression of CYP76B75 was significantly up-regulated. Therefore, this study confirmed that when the expression of CYP76B75 and CYP76B100 were interrupted, the growth of hairy roots were suppressed, but the synthesis of shikonin were promoted. They might increase the shikonin biosynthesis by up-regulating the expression of CYP76B74 in the hairy roots of A. euchroma.


Subject(s)
Boraginaceae , Genetics , Cytochrome P-450 Enzyme System , Naphthoquinones , Phylogeny , Plant Roots , RNA , RNA Interference
3.
Chinese Journal of Biotechnology ; (12): 1346-1355, 2020.
Article in Chinese | WPRIM | ID: wpr-826842

ABSTRACT

Cytochrome P450 monooxygenases as powerful biocatalysts catalyze a wide range of chemical reactions to facilitate exogenous substances metabolism and biosynthesis of natural products. In order to explore new catalytic reactions and increase the number of P450 biocatalysts used in synthetic biology, a new self-sufficient cytochrome P450 monooxygenase (P450(VpMO)), belongs to CYP116B class, was mined from Variovorax paradoxus S110 genome and expressed in Escherichia coli. Based on characterization of the enzymatic properties, it shows that the optimal pH and temperature for P450(VpMO) reaction activity are 8.0 and 45 °C, respectively. P450(VpMO) is relatively stable at temperatures below 35 °C. The Km and kcat of P450(VpMO) toward 4-Methoxyacetophenone are 0.458 mmol/L and 2.438 min⁻¹, respectively. Importantly, P450(VpMO) was able to catalyze the demethylation reaction for a range of substrates containing methoxy group. Its demethylation reactivity is reasonably better than other P450s belongs to CYP116B class, particularly, for 4-methoxyacetophenone with a great conversion efficiency at 91%, showing that P450(VpMO) could be used as a great biocatalyst candidate for further analysis.


Subject(s)
Catalysis , Comamonadaceae , Genetics , Cytochrome P-450 Enzyme System , Genetics , Metabolism , Gene Expression , Synthetic Biology
4.
Braz. j. infect. dis ; 23(6): 381-387, Nov.-Dec. 2019. tab, graf
Article in English | LILACS | ID: biblio-1089317

ABSTRACT

ABSTRACT Setting: Treatment of tuberculosis (TB) can result in Drug-Induced Liver Injury (DILI) since hepatotoxic metabolites are formed during the biotransformation of isoniazid (INH).DILI can be related to the genetic profile of the patient. Single nucleotide polymorphisms in the CYP2E1 gene and GSTM1 and GSTT1 deletion polymorphisms have been associated with adverse events caused by INH. Objective: To characterize the genetic polymorphisms of CYP2E1, GSTT1 and GSTM1 in TB carriers. Design: This is an observational prospective cohort study of 45 patients undergoing treatment of TB. PCR-RFLP and multiplex-PCR were used. Results: The distribution of genotypic frequency in the promoter region (CYP2E1 gene) was: 98% wild genotype and 2% heterozygous. Intronic region: 78% wild genotype; 20% heterozygous and 2% homozygous variant. GST enzyme genes: 24% Null GSTM1 and 22% Null GSTT1. Patients with any variant allele of the CYP2E1 gene were grouped in the statistical analyses. Conclusion: Patients with the CYP2E1 variant genotype or Null GSTT1 showed higher risk of presenting DILI (p = 0.09; OR: 4.57; 95% CI: 0.75-27.6). Individuals with both genotypes had no increased risk compared to individuals with one genotype.


Subject(s)
Humans , Male , Female , Adolescent , Adult , Middle Aged , Aged , Aged, 80 and over , Young Adult , Tuberculosis, Pulmonary/drug therapy , Genetic Predisposition to Disease/genetics , Chemical and Drug Induced Liver Injury/genetics , Antitubercular Agents/adverse effects , Polymorphism, Genetic , Tuberculosis, Pulmonary/enzymology , Prospective Studies , Cytochrome P-450 CYP2E1 , Cytochrome P-450 Enzyme System/genetics , Chemical and Drug Induced Liver Injury/enzymology , Cytochrome P450 Family 2 , Genotype , Liver/drug effects , Liver/enzymology , Antitubercular Agents/therapeutic use
5.
Article in Chinese | WPRIM | ID: wpr-773677

ABSTRACT

Cytochrome P450 family is a kind of biocatalyst widely existing in nature. It has many functions such as catalyzing the biosynthesis of plant secondary metabolites and regulating phytoremediation. Based on the analysis of proteome data of Tripterygium wilfordii,the CYP450 gene of T. wilfordii was preliminarily analyzed and predicted by various bioinformatics methods. The results showed that after the expression of T. wilfordii suspension cells was induced by methyl jasmonate,the proteomic data of T. wilfordii were obtained and analyzed,and 10 CYP450 proteins of T. wilfordii were finally screened out. By analyzing the phylogenetic tree constructed with CYP450 gene of Arabidopsis family,the 10 CYP450 proteins were clustered into 6 different CYP450 families. The physical and chemical properties of CYP450 proteins in different families were different. The secondary structure of CYP450 proteins was mainly composed of irregular curls. Eight subcellular localization results of CYP450 proteins were chloroplasts and the rest were plastids. Subsequently,the conserved domains( heme active sites) shared by CYP450 genes were found by analyzing the results of multiple sequence alignment. Finally,by analyzing the transcriptome data of T. wilfordii,the expression distribution of T. wilfordii in different tissues was preliminarily confirmed,which verified its correlation with the biosynthesis of active components of T. wilfordii,and provided important genetic resources for the analysis of biosynthesis pathway of active components of T. wilfordii.


Subject(s)
Computational Biology , Cytochrome P-450 Enzyme System , Chemistry , Phylogeny , Plant Proteins , Chemistry , Proteomics , Tissue Distribution , Tripterygium
6.
Article in Chinese | WPRIM | ID: wpr-773236

ABSTRACT

Tanshinones are abietane-type norditerpenoid quinones that make up the main bioactive ingredients of traditional Chinese medicine Salvia miltiorrhiza. Cytochrome CYP450 plays an important role in the post-structural modification of tanshinone biosynthesis pathway. Long non-coding RNA( lncRNA) have been defined as transcripts longer than 200 nucleotides,which have been functionally characterized in regulating the growth and development,secondary metabolism and stress of medicinal plants. In this study,we perform a comprehensive identification of lncRNAs in response to tanshinone metabolism induced by yeast extract( YE) and Ag~+ S. miltiorrhiza hairy roots. Deep RNA sequencing was used to identify a set of different 8 942 lncRNAs,of which 6 755 were intergenic lncRNAs. We predicted a total of 1 115 814 lncRNA-coding gene pairs,including 122 lncRNA-coding gene as cis pairs. The correlation analysis between lncRNA and CYP450 related to tanshinone biosynthesis was carried out and a total of 16 249 lncRNA-CYP450 target gene pairs were identified. Further analysis with functional known CYP76 AH1,CYP76 AH3 and CYP76 AK1 involved in tanshinone biosynthesis,we also identified a set of 216 target genes. These candidate genes will be the important target in the downstream regulation mechanism analysis of the tanshinone biosynthesis pathway.


Subject(s)
Cytochrome P-450 Enzyme System , Genetics , Abietanes , Gene Expression Regulation, Plant , Plant Roots , RNA, Long Noncoding , Genetics , RNA, Plant , Genetics , Salvia miltiorrhiza , Genetics
7.
Article in English | WPRIM | ID: wpr-776900

ABSTRACT

Anemone flaccida Fr. Schmidt is a perennial medicinal herb that contains pentacyclic triterpenoid saponins as the major bioactive constituents. In China, the rhizomes are used as treatments for a variety of ailments including arthritis. However, yields of the saponins are low, and little is known about the plant's genetic background or phytohormonal responsiveness. Using one-quarter of the 454 pyrosequencing information from the Roche GS FLX Titanium platform, we performed a transcriptomic analysis to identify 157 genes putatively encoding 26 enzymes involved in the synthesis of the bioactive compounds. It was revealed that there are two biosynthetic pathways of triterpene saponins in A. flaccida. One pathway depends on β-amyrin synthase and is similar to that found in other plants. The second, subsidiary ("backburner") pathway is catalyzed by camelliol C synthase and yields β-amyrin as minor byproduct. Both pathways used cytochrome P450-dependent monooxygenases (CYPs) and family 1 uridine diphosphate glycosyltransferases (UGTs) to modify the triterpenoid backbone. The expression of CYPs and UGTs were quite different in roots treated with the phytohormones methyl jasmonate, salicylic acid and indole-3-acetic acid. This study provides the first large-scale transcriptional dataset for the biosynthetic pathways of triterpene saponins and their phytohormonal responsiveness in the genus Anemone.


Subject(s)
Anemone , Genetics , Metabolism , Biosynthetic Pathways , Genetics , Cytochrome P-450 Enzyme System , Genetics , Metabolism , Gene Expression Profiling , Gene Expression Regulation, Plant , Glycosyltransferases , Genetics , Metabolism , Oleanolic Acid , Metabolism , Plant Growth Regulators , Pharmacology , Plant Proteins , Genetics , Metabolism , Plants, Medicinal , Rhizome , Genetics , Metabolism , Saponins , Metabolism , Triterpenes , Metabolism
8.
Article in Chinese | WPRIM | ID: wpr-776751

ABSTRACT

OBJECTIVE@#To explore the genetic basis for a child affected with multiple malformations.@*METHODS@#Genomic DNA was extracted from peripheral blood samples from the child and her parents. Tro whole exome sequencing and bioinformatics analysis were carried out. Suspicted mutations were verified by PCR and Sanger sequencing.@*RESULTS@#The patient, a 2-year-old girl, presented with multiple malformations including dysmorphism, skeletal malformations and ambigulous genitalia. Through genetic testing, she was diagnosed with Antley-Bixler syndrome caused by compound heterozygous mutations of the POR gene (c.919G>T and c.1615G>A), which were derived from her mother and father, respectively.@*CONCLUSION@#The compound heterozygous mutations of the POR gene probably underlie the Antley-Bixler syndrome in this patient.


Subject(s)
Abnormalities, Multiple , Genetics , Antley-Bixler Syndrome Phenotype , Genetics , Child, Preschool , Cytochrome P-450 Enzyme System , Genetics , Female , Humans , Mutation , Whole Exome Sequencing
9.
Gut and Liver ; : 450-460, 2019.
Article in English | WPRIM | ID: wpr-763854

ABSTRACT

BACKGROUND/AIMS: For the clinical application of stem cell therapy, functional enhancement is needed to increase the survival rate and the engraftment rate. The purpose of this study was to investigate functional enhancement of the paracrine effect using stem cells and hepatocyte-like cells and to minimize stem cell homing by using a scaffold system in a liver disease model. METHODS: A microporator was used to overexpress Foxa2 in adipose tissue-derived stem cells (ADSCs), which were cultured in a poly(lactic-co-glycolic acid) (PLGA) scaffold. Later, the ADSCs were cultured in hepatic differentiation medium for 2 weeks by a 3-step method. For in vivo experiments, Foxa2-overexpressing ADSCs were loaded in the scaffold, cultured in hepatic differentiation medium and later were implanted in the dorsa of nude mice subjected to acute liver injury (thioacetamide intraperitoneal injection). RESULTS: Foxa2-overexpressing ADSCs showed greater increases in hepatocyte-specific gene markers (alpha fetoprotein [AFP], cytokeratin 18 [CK18], and albumin), cytoplasmic glycogen storage, and cytochrome P450 expression than cells that underwent the conventional differentiation method. In vivo experiments using the nude mouse model showed that 2 weeks after scaffold implantation, the mRNA expression of AFP, CK18, dipeptidyl peptidase 4 (CD26), and connexin 32 (CX32) was higher in the Foxa2-overexpressing ADSCs group than in the ADSCs group. The Foxa2-overexpressing ADSCs scaffold treatment group showed attenuated liver injury without stem cell homing in the thioacetamide-induced acute liver injury model. CONCLUSIONS: Foxa2-overexpressing ADSCs applied in a scaffold system enhanced hepatocyte-like differentiation and attenuated acute liver damage in an acute liver injury model without homing effects.


Subject(s)
Animals , Cytochrome P-450 Enzyme System , Cytoplasm , Dipeptidyl Peptidase 4 , Fetal Proteins , Glycogen , Keratin-18 , Liver Diseases , Liver Failure, Acute , Liver , Mesenchymal Stem Cells , Methods , Mice , Mice, Nude , RNA, Messenger , Stem Cells , Survival Rate
10.
Article in English | WPRIM | ID: wpr-763043

ABSTRACT

Human cytochrome P450 2C9 is a highly polymorphic enzyme that is required for drug and xenobiotic metabolism. Here, we studied eleven P450 2C9 genetic variants—including three novel variants F69S, L310V, and Q324X—that were clinically identified in Korean patients. P450 2C9 variant enzymes were expressed in Escherichia coli and their bicistronic membrane fractions were prepared The CO-binding spectra were obtained for nine enzyme variants, indicating P450 holoenzymes, but not for the M02 (L90P) variant. The M11 (Q324X) variant could not be expressed due to an early nonsense mutation. LC-MS/MS analysis was performed to measure the catalytic activities of the P450 2C9 variants, using diclofenac as a substrate. Steady-state kinetic analysis revealed that the catalytic efficiency of all nine P450 2C9 variants was lower than that of the wild type P450 2C9 enzyme. The M05 (R150L) and M06 (P279T) variants showed high k(cat) values; however, their K(m) values were also high. As the M01 (F69S), M03 (R124Q), M04 (R125H), M08 (I359L), M09 (I359T), and M10 (A477T) variants exhibited higher K(m) and lower k(cat) values than that of the wild type enzyme, their catalytic efficiency decreased by approximately 50-fold compared to the wild type enzyme. Furthermore, the novel variant M07 (L310V) showed lower k(cat) and K(m) values than the wild type enzyme, which resulted in its decreased (80%) catalytic efficiency. The X-ray crystal structure of P450 2C9 revealed the presence of mutations in the residues surrounding the substrate-binding cavity. Functional characterization of these genetic variants can help understand the pharmacogenetic outcomes.


Subject(s)
Codon, Nonsense , Cytochrome P-450 Enzyme System , Cytochromes , Diclofenac , Escherichia coli , Holoenzymes , Humans , Membranes , Metabolism , Pharmacogenetics
11.
Braz. j. microbiol ; 49(4): 749-756, Oct.-Dec. 2018. tab, graf
Article in English | LILACS | ID: biblio-974295

ABSTRACT

ABSTRACT Pyrene and benzo[a]pyrene (BaP) are high molecular weight polycyclic aromatic hydrocarbons (PAHs) recalcitrant to microbial attack. Although studies related to the microbial degradation of PAHs have been carried out in the last decades, little is known about degradation of these environmental pollutants by fungi from marine origin. Therefore, this study aimed to select one PAHs degrader among three marine-derived basidiomycete fungi and to study its pyrene detoxification/degradation. Marasmiellus sp. CBMAI 1062 showed higher levels of pyrene and BaP degradation and was subjected to studies related to pyrene degradation optimization using experimental design, acute toxicity, organic carbon removal (TOC), and metabolite evaluation. The experimental design resulted in an efficient pyrene degradation, reducing the experiment time while the PAH concentration applied in the assays was increased. The selected fungus was able to degrade almost 100% of pyrene (0.08 mg mL-1) after 48 h of incubation under saline condition, without generating toxic compounds and with a TOC reduction of 17%. Intermediate metabolites of pyrene degradation were identified, suggesting that the fungus degraded the compound via the cytochrome P450 system and epoxide hydrolases. These results highlight the relevance of marine-derived fungi in the field of PAH bioremediation, adding value to the blue biotechnology.


Subject(s)
Polycyclic Aromatic Hydrocarbons/metabolism , Seawater/microbiology , Basidiomycota/metabolism , Phylogeny , Polycyclic Aromatic Hydrocarbons/chemistry , Pyrenes/metabolism , Pyrenes/chemistry , Basidiomycota/isolation & purification , Basidiomycota/classification , Basidiomycota/genetics , Benzo(a)pyrene/metabolism , Benzo(a)pyrene/chemistry , Biodegradation, Environmental , Fungal Proteins/genetics , Fungal Proteins/metabolism , Cytochrome P-450 Enzyme System/genetics , Cytochrome P-450 Enzyme System/metabolism
13.
Electron. j. biotechnol ; 32: 35-40, Mar. 2018. ilus, tab
Article in English | LILACS | ID: biblio-1022620

ABSTRACT

Background: Poor reproductive efficiency of river buffalos hampers the production capabilities of animals. Buffalos are mainly considered poor breeders owing to the constrained expression of estrus behavior. Failure to display heat signs is an indication of improper functionality of signaling peptides to trigger on a series of behavioral changes, which can be detectable by breeders for timely insemination of females. This might cause an animal to be a repeat breeder. Genomic variations underlying synthesis of signaling peptides can be a useful marker to select superior animals with better reproductive efficiency. In this context, the current study was designed to analyze the CYP19A1 gene in Nili-Ravi buffalo. Results: A total of 97 animals were selected and were divided into two groups on the basis of their heat score. PCR amplification and sequencing of the amplicons were performed using the specific sets of primer, and then, sequences were analyzed for novel variants. A total of 11 polymorphic sites were identified illustrating phenotypic variation in the heat score. Most of the loci were found homologous. Single Nucleotide Polymorphisms (SNPs) were analyzed for association with silent estrus. A three-dimensional protein model was also generated to locate the position of exonic SNPs. Conclusion: This study illustrated that polymorphic sites in the CYP19A1 gene provided potential markers for selection of buffalos with better estrus behavior.


Subject(s)
Animals , Female , Pregnancy , Estrus/genetics , Buffaloes/genetics , Aromatase/genetics , Cytochrome P-450 Enzyme System/genetics , Pakistan , Selection, Genetic , Breeding , Polymerase Chain Reaction , Polymorphism, Single Nucleotide , Intracellular Signaling Peptides and Proteins , Insemination
14.
Rev. méd. Minas Gerais ; 28: [1-9], jan.-dez. 2018.
Article in Portuguese | LILACS | ID: biblio-967878

ABSTRACT

Medicamentos com atividade sobre a mesma família de enzimas do citocromo P450 (CYP450), quando administrados concomitantemente, podem interagir entre si e afetar o clearance sistêmico de um dos fármacos, resultando em redução da efetividade ou aumento da toxicidade do medicamento afetado. O presente estudo tem como objetivo determinar a prevalência de uso de medicamentos com atividade sobre isoenzimas do CYP450 por pacientes idosos em domicílio. Trata-se de um estudo transversal, retrospectivo, descritivo, realizado em hospital público geral de ensino de Belo Horizonte, Minas Gerais. Foram incluídos no estudo 190 pacientes com 60 anos ou mais, internados de janeiro a dezembro de 2010 na enfermaria de clínica médica do hospital e em uso domiciliar de medicamentos com registro no prontuário. Os fármacos com atividade sobre as isoenzimas da família CYP450 foram classificados em indutores, inibidores ou substratos segundo literatura especializada. Dentre os 190 idosos incluídos na investigação, 99 (52,1%) eram do sexo feminino. A mediana da idade foi 69,5 e intervalo interquartil (IQR)12. Foi observado que 172 pacientes (90,5%) utilizaram algum fármaco com atividade sobre CYP450. Em relação aos fármacos utilizados, verificouse que 94 (59,1 %) exerciam atividade sobre enzimas do CYP450, o que implica em alto potencial para ocorrência de interações medicamentosas. Fica evidente a importância da informação acerca da atividade dos fármacos sobre o CYP450, para subsidiar as decisões clínicas em relação à farmacoterapia do idoso, contribuindo assim para maior segurança e efetividade no uso dos medicamentos. (AU)


Drugs that act on the same family of CYP450 enzymes, when administered concurrently, may interact among themselves and affect the systemic clearance of one of the drugs, reducing the effectiveness or increasing the toxicity of the affected medication. The present study aims to determine the prevalence use of drugs by elderly patients at home with activity on CYP450 isoenzymes. This is a cross-sectional, retrospective, descriptive study executed at a general public teaching hospital in Belo Horizonte, Minas Gerais. A hundred ninety patients with 60 years or older, admitted to internal medicine ward of the hospital from January to December 2010 and who had medical records of medicine used at home were included in the study. Drugs with activity on CYP450 isoenzymes family were classified into inducers, inhibitors or substrates according specialized literature. Among the 190 elderly included in the investigation, 99 (52.1%) were from the female gender. The median age was of 69.5 and interquartile range (IQR) 12. It was observed that 172 patients (90.5%) used any drug with activity on CYP450. Concerning the drugs used, it was found that 94 (59.1%) had activity on CYP450 enzymes, what implicates in a high potential to the occurrence of drugdrug interactions. It becomes evident the importance of information about the activity of drugs on CYP450, to subsidize the clinical decisions concerning the geriatric pharmacotherapy, therefore contributing to a higher security and effectiveness in the medications usage. (AU)


Subject(s)
Humans , Male , Female , Aged , Aged, 80 and over , Pharmacologic Actions , Cytochrome P-450 Enzyme System , Biopharmaceutics , Pharmacokinetics , Pharmaceutical Preparations , Frail Elderly , Drug Therapy
15.
Article in Chinese | WPRIM | ID: wpr-775340

ABSTRACT

This study was carried out to investigate the effect of oral administration of Dendrobium huoshanense on the expressions and activities of hepatic microsomal cytochrome P450s in mice, and to provide a reference for the evaluation of drug-drug interactions between D. huoshanense and clinical drugs. The C57BL/6 mice were randomly divided into blank control group, D. huoshanense low dose group (crude drug 1.25 g·kg⁻¹), D. huoshanense high dose group (crude drug 7.5 g·kg⁻¹), and phenobarbital positive control group (0.08 g·kg⁻¹). Each group was intragastrically administered with drugs for 2 weeks. The mice were sacrificed and their liver microsomes were prepared. The expressions of major subtypes of P450 enzyme were determined by Western blot and the probe drugs were used to detect the enzyme activities of P450 subtypes with protein expression changes. Western blot analysis showed that the protein expressions of CYP1A1, CYP1A2 and CYP2B in liver tissues were up-regulated in D. huoshanense-treated group. In vitro enzyme activity tests showed that there were no significant difference in metabolism of 7-ethoxyresorufin (a probe drug for CYP1A1) and bupropion (a probe drug for CYP2B) between D. huoshanense group and control group. The metabolism of phenacetin (a probe drug for CYP1A2) showed a statistical difference in rate Vmax, and it was significantly increased by approximately 20% in D. huoshanense group as compared with the blank control group, and the clearance CLint in treated group was also increased by about 32%. Therefore, oral administration of D. huoshanense had no effects on the activities of most hepatic P450 enzymes in mice, with no drug-drug interaction related to the P450 enzyme system in most clinical drugs theoretically. However, oral administration of D. huoshanense may accelerate the metabolism of CYP1A2-catalyzed drugs, which needs to be considered in clinical practice.


Subject(s)
Animals , Cytochrome P-450 CYP1A1 , Metabolism , Cytochrome P-450 CYP1A2 , Metabolism , Cytochrome P-450 Enzyme System , Metabolism , Dendrobium , Chemistry , Drugs, Chinese Herbal , Pharmacology , Mice , Mice, Inbred C57BL , Microsomes, Liver , Random Allocation
16.
Article in Chinese | WPRIM | ID: wpr-771727

ABSTRACT

This study aimed to investigate the effect and mechanism of ophiopogonin D (OP-D) on Ang Ⅱ-induced HUVECs apoptosis, in order to provide a reliable basis for the safety and efficacy of traditional Chinese medicines. The effect of Ang Ⅱ on survival and total proteins content of HUVECs were measured by MTT and Western blotting. The effect of OP-D on Ang Ⅱ-induced lactate dehydrogenase (LDH) release rate in HUVECs was measured by enzyme standard instrument. The effects of OP-D and 11,12-EET on phosphorylation of JNK/c-Jun induced by Ang Ⅱ were measured by Western blot and RT-PCR with the help of JNK specific inhibitor SP600125 and CYP450 isozymes selective inhibitor 6-(2-propargyloxyphenyl) hexanoic acid (PPOH). The cell apoptosis was assayed by flow cytometry. According to the results, different doses of Ang Ⅱ had no significant effect on cell survival; treatment with Ang Ⅱ at 1×10⁻⁶ mol·L⁻¹ could increase the release of LDH (<0.001). The phosphorylation of JNK and c-Jun could be inhibited by the pre-treatment with SP600125, 11,12-EET and OP-D. Pre-treatment with OP-D could significantly reduce the release of LDH induced by Ang Ⅱ stimulation, decrease the expression of caspase-3, and diminish the apoptosis of cells. The protective effect of OP-D was suppressed, when being pretreated with PPOH. The experimental results showed that the apoptosis of HUVECs induced by Ang Ⅱ may be associated with JNK/c-Jun signaling pathway. OP-D-mediated CYP2J2 expression increased 11,12-EET levels, and could remarkably resist Ang Ⅱ-induced injury and apoptosis of cells, which is associated with the maintenance of endothelium homeostasis.


Subject(s)
Angiotensin II , Apoptosis , Arachidonic Acids , Metabolism , Cells, Cultured , Cytochrome P-450 Enzyme System , Metabolism , Human Umbilical Vein Endothelial Cells , Cell Biology , Humans , Phosphorylation , Saponins , Pharmacology , Signal Transduction , Spirostans , Pharmacology
17.
Article in Chinese | WPRIM | ID: wpr-771553

ABSTRACT

Schisandra chinensis is a commonly used hepatoprotective medicine in clinic. Previous studies have showed that Schisandrae Chinensis Fructus has dual effects on the activity of CYPs. Short-term administration of Schisandrae Chinensis Fructus may inhibit CYP450s activity, while long-term administration may up-regulate CYP activity. High CYP450s activity level may increase the frequency of reactive metabolites-induced liver injury. It remains unclear how long-term administration of Schisandrae Chinensis Fructus may affect acetaminophen-induced acute hepatotoxicity. After oral administration of Schisandrae Chinensis Fructus extract (0.5-2.0 g·kg⁻¹) for 21 d, the activity of CYPs, Nrf2, HO-1, GST expressions, SOD and GST activity as well as glutathione level of SD rats were up-regulated. Besides, Schisandrae Chinensis Fructus extract ameliorated APAP (500 mg·kg⁻¹)-induced acute hepatotoxicity in a dose-dependent manner, as evidenced by decrease in ALT, AST, and MDA level and increase in GSH level (<0.05). What's more, the liver histopathology was alleviated, and cleaved caspase-3 expression was decreased. Besides, the increase of N-acetyl-p-benzoquinoneimine-GSH (reactive metabolite of acetaminophen) formation was observed in Schisandrae Chinensis Fructus extract groups. In conclusion, the present study indicated that the effects of Schisandrae Chinensis Fructuson acetaminophen-induced hepatotoxicity may rely on the Nrf2 signal pathway activation, and less depends on the increase in CYP450s activity.


Subject(s)
Acetaminophen , Animals , Chemical and Drug Induced Liver Injury , Cytochrome P-450 Enzyme System , Drugs, Chinese Herbal , Liver , NF-E2-Related Factor 2 , Rats , Rats, Sprague-Dawley
18.
Acta Physiologica Sinica ; (6): 591-599, 2018.
Article in English | WPRIM | ID: wpr-777226

ABSTRACT

Kidney diseases are important causes of mortality world widely. Renal microvascular dysfunction plays a pivotal role in the development of kidney diseases. Pharmacological and biochemical tools have been used to conduct detailed studies on the metabolization of arachidonic acid by cytochrome P450 (CYP450) in renal microvasculature. CYP450 epoxygenase metabolites epoxyeicosatrienoic acids (EETs) are mainly produced in renal microvessels. EETs exhibit renoprotective effects through vasodilation, anti-hypertension, anti-apoptosis and anti-inflammation, and were reported as therapeutic targets of renal diseases. However, the ability of the kidney in generating EETs is reduced in renal diseases. Recently, the studies from transgenic animal overexpressing CYP450 epoxygenases and application of soluble epoxide hydrolase inhibitors revealed that increasing of EETs exhibits renoprotective effects in vivo. The present review focuses on the protective mechanisms of EETs in kidney physiology and diseases.


Subject(s)
Animals , Animals, Genetically Modified , Arachidonic Acid , Metabolism , Cytochrome P-450 Enzyme System , Physiology , Disease Models, Animal , Humans , Inflammation , Kidney , Physiology , Kidney Diseases , Vasodilation
19.
Article in Chinese | WPRIM | ID: wpr-776424

ABSTRACT

To investigate the effects of the expression of flavonoid 3' hydroxylase gene ( and active ingredients in under flooding stress, we cloned F3'H from Hangju (temporarily named ) and conducted bioinformatics analysis. During the flower bud differentiation stage, we flooded the and then used the Real-time PCR to detect the relative expression of ; Finally, active ingredients of the inflorescence were measured by HPLC.The sequencing results showed that 1 562 bp sequence was acquired with the largest open reading frame of 1 527 bp, which encoded 508 amino acids. The phylogenetic tree found that was highly homologous to other species of Compositae. Real-time PCR results showed that had a significant response to flooding stress and had the highest expression level after flooding for 24 h, which was about 9 times as that of the control group. The results of HPLC showed that luteolin and luteoloside, the downstream products catalyzed by the F3'H, were significantly higher than those in the control group. It was also found that the contents of chlorogenic acid and 3,5- acid were also significantly higher than those of the control group. Therefore, regulates the synthesis of downstream products by regulating the expression of in the flavonoid synthesis pathway under flooding stress, thereby responding to flooding stress. The flooding stress during flower bud differentiation can significantly enhance the accumulation of active ingredients.


Subject(s)
Chrysanthemum , Genetics , Cloning, Molecular , Cytochrome P-450 Enzyme System , Genetics , Floods , Gene Expression Regulation, Plant , Glucosides , Luteolin , Phylogeny , Plant Proteins , Genetics , Stress, Physiological
20.
Article in Chinese | WPRIM | ID: wpr-687959

ABSTRACT

Antley-Bixler syndrome (ABS) is a rare childhood disorder affecting skeletal development. Some patients may also have genital anomalies and impaired steroidogenesis. Diagnostic criteria for ABS has not been fully established, though craniosynostosis, midface hypoplasia and elbow synostosis are minimum requirements. The etiology of ABS is complex, which included autosomal dominant form caused by FGFR2 gene mutations, autosomal recessive form caused by POR gene mutations, and high oral dose of fluconazole during pregnancy. Patients may die from dyspnea due to upper respiratory tract obstruction. This review summarizes research progress on the clinical features, etiology, differential diagnosis, treatment and prevention of ABS.


Subject(s)
Animals , Antley-Bixler Syndrome Phenotype , Diagnosis , Genetics , Therapeutics , Cytochrome P-450 Enzyme System , Genetics , Diagnosis, Differential , Fetus , Fluconazole , Humans , Receptor, Fibroblast Growth Factor, Type 2 , Genetics
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