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CYP450 enzymes

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https://read.qxmd.com/read/30877061/effects-of-formaldehyde-on-detoxification-and-immune-responses-in-silver-pomfret-pampus-argenteus
#1
Jiabao Hu, Qijun Le, Yajun Wang, Na Yu, Xiaohuan Cao, Siwen Kuang, Man Zhang, Weiwei Gu, Yibo Sun, Yang Yang, Shanliang Xu, Xiaojun Yan
Formaldehyde can effectively control ectoparasites in the silver pomfret (Pampus argenteus). However, there is limited information on the effects of formaldehyde treatment at a molecular level in the fish. In the present study, transcriptome profiling was conducted to investigate the effects of formaldehyde treatment (80 mg/L, bath for 1 h every day for three consecutive days) on the liver and kidney of silver pomfret. A total of 617959982 clean reads were obtained and assembled into 265760 unigenes with an N50 length of 1507 bp, and the assembled unigenes were all annotated by alignment with public databases...
March 12, 2019: Fish & Shellfish Immunology
https://read.qxmd.com/read/30865484/cytotoxicity-of-safrole-in-heparg-cells-studies-on-the-role-of-cyp1a2-mediated-ortho-quinone-metabolic-activation
#2
Linlin Hu, Hua Shao, Jie He, Lingjun Zhong, Yifan Song, Fei Wu
Safrole is a natural compound categorized as a group 2B carcinogen extracted from sassafras oil or certain other essential oils. The hepatotoxicity of safrole has always been highly concerned. So the purpose of this study was to evaluate the role of cytochrome P450 (CYP450)-mediated reactive metabolites (RMs) formation and its induced cytotoxicity in HepaRG cells. Safrole belongs to the methylenedioxyphenyl structure which could be activated to RMs. Two metabolites (M1, M2) and three new glutathione conjugates (M3-M5) of safrole ortho-oquinone RMs were found in HepaRG cells...
March 13, 2019: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://read.qxmd.com/read/30864366/evaluation-of-correlation-between-the-pharmacogenetic-profiles-of-risperidone-treated-psychiatry-patients-with-plasma-and-urine-concentration-of-risperidone-and-its-active-moiety-9-oh-risperidone-determined-with-optimized-bioanalytical-lc-method
#3
Ana Filipce, Zorica Naumovska, Aleksandra Kapedanovska Nestorovska, Zoran Sterjev, Katerina Brezovska, Jasmina Tonic-Ribarska, Aleksandra Grozdanova, Ljubica Suturkova, Marija Raleva
Atypical antipsychotic risperidone is widely used first-line monotherapy in schizophrenia and combined therapy in bipolar disorders. Therapeutic plasma concentrations of risperidone and its active moiety are directly influenced by genetic variations in metabolic CYP450 enzymes (CYP2D6 and CYP3A4/5) and transporter (ABCB1) protein and additional environmental factors. Since active metabolite 9-OH risperidone has a greater percentage of the pharmacologically active fraction and is equipotent to the parent drug risperidone, it is assumed that it contributes significantly to therapeutic and adverse effects...
December 1, 2018: Prilozi (Makedonska Akademija Na Naukite i Umetnostite. Oddelenie za Medicinski Nauki)
https://read.qxmd.com/read/30838457/selective-serotonin-reuptake-inhibitors
#4
Dee Lochmann, Tara Richardson
The first antidepressants were created by chance but brought the idea that central serotonin agonism produced an antidepressant effect. SSRIs were the first class of psychotropic medications to be rationally designed, meaning that researchers intended to utilize a specific mechanism of action while avoiding adverse effects. In this way, SSRIs were created to be safer and more tolerable than previous antidepressants. SSRIs share many similarities, but differ in terms of pharmacokinetics and effects on CYP450 enzymes, which is detailed in this chapter...
March 6, 2019: Handbook of Experimental Pharmacology
https://read.qxmd.com/read/30809922/pharmacogenetic-variants-in-bipolar-disorder-with-elevated-treatment-resistance-and-intolerance-towards-a-personalised-pattern-of-care
#5
Cecilia Casetta, Cristina Montrasio, Stefania Cheli, Sara Baldelli, Ivonne Bianchi, Emilio Clementi, Orsola Gambini, Armando D'Agostino
BACKGROUND: Clinical psychiatry has recently begun to promote a personalised approach to care that can offer the best patient-tailored treatment in terms of efficacy and tolerability. Although still in its infancy, pharmacogenetic profiling is one of the most promising tools in a comprehensive, individualized assessment of the patient. CASE REPORT: We present the case of a woman with treatment-resistant Bipolar Disorder, whose life has been ravaged by continuous hospitalizations for severe manic and depressive episodes...
February 27, 2019: Bipolar Disorders
https://read.qxmd.com/read/30804010/cyp79d73-participates-in-biosynthesis-of-floral-scent-compound-2-phenylethanol-in-plumeria-rubra
#6
Savitha Dhandapani, Jingjing Jin, Vishweshwaran Sridhar, Nam-Hai Chua, In-Cheol Jang
Plumeria (Plumeria rubra), well-known for its brightly colored and fragrant flowers, emits a number of floral volatile organic compounds (VOCs). Plumeria flowers emit a total of 43 VOCs including nine phenylpropanoids/benzenoids, such as 2-phenylethanol (2PE), benzaldehyde, 2-phenylacetaldehyde (PAld), (E/Z)-phenylacetaldoxime (PAOx), benzyl nitrile (BN), and 2-phenylnitroethane (PN). To identify genes and pathways involved in the production of the major compound 2PE, we analyzed the plumeria floral transcriptome and found a highly expressed, flower-specific gene encoding a cytochrome P450 (CYP450) family 79D protein (PrCYP79D73), which catalyzed the formation of (E/Z)-PAOx...
February 25, 2019: Plant Physiology
https://read.qxmd.com/read/30800683/influences-of-corydalis-decumbens-on-the-activities-of-cyp450-enzymes-in-rats-with-a-cocktail-approach
#7
Chen Cheng, Jianchang Qian, Zhe Wang, Wanshu Li, Chengke Huang, Mengchun Chen, Yaoyao Dong, Lejing Lian, Wei Sun
Corydalis decumbens , a Traditional Chinese Medicine, has been widely used for the alternative and/or complementary therapy of hypertension, arrhythmias rheumatoid arthritis, sciatica, stroke, hemiplegia, paraplegia, and vascular embolism. The aim of this study was to determinate the potential effects of Corydalis decumbens on the five cytochrome P450 (CYP) enzyme activities (CYP1A2, CYP3A4, CYP2C9, CYP2C19, and CYP2D6) by cocktail approach. To evaluate whether concurrent use of Corydalis decumbens interferes with the effect of several prescription drugs, saline (control group) or Corydalis decumbens (XTW group) were administrated via gavage for 7 successive days...
2019: BioMed Research International
https://read.qxmd.com/read/30772481/tenacigenin-b-ester-derivatives-from-marsdenia-tenacissima-actively-inhibited-cyp3a4-and-enhanced-in-vivo-antitumor-activity-of-paclitaxel
#8
Bin Xie, Yuan-Yuan Lu, Zhuo-Hui Luo, Zhao Qu, Chun-Ge Zheng, Xin-An Huang, Hong-Yan Zhou, Ying-Jie Hu, Xiao-Ling Shen
ETHNOPHARMACOLOGICAL RELEVANCE: Marsdenia tenacissima (Roxb.) Wight et Arn is a vine distributed in southwest area of China and used in folk medicine for treatment of tumors. Recent decades of studies on this plant reveal its synergistic effects with certain anticancer drugs in cancer therapy. In our previous study, an extract ETA which contains total aglycones made from M. tenacissima significantly enhanced antitumor activity of paclitaxel in tumor-bearing mice. However, the effective constituents inETA and the underlying mechanisms remain unclear...
February 14, 2019: Journal of Ethnopharmacology
https://read.qxmd.com/read/30772286/development-of-caco-2-cells-based-gene-reporter-assays-and-evaluation-of-herb-drug-interactions-involving-cyp3a4-and-cyp2d6-gene-expression
#9
Clarissa Feltrin, Paula Freire Brambila, Cláudia Maria Oliveira Simões
The indiscriminate use of medicinal plants and herbal medicinal products concomitantly with conventional drugs may result in herb-drug interactions that may lead to fluctuations in drug bioavailability, therapeutic failure, and/or toxic effects. CYP450 enzymes play an important role in drug biotransformation and herb-drug interactions. Thus, the aim of this study was to develop and apply Caco-2 cells-based gene reporter assays to study in vitro the potential occurrence of CYP3A4 and CYP2D6 gene expression modulation by standardized extracts of selected medicinal plants...
February 14, 2019: Chemico-biological Interactions
https://read.qxmd.com/read/30767228/berry-transcriptome-insights-into-a-novel-resource-to-understand-development-dependent-secondary-metabolism-in-withania-somnifera-ashwagandha
#10
Sandhya Tripathi, Rajender Singh Sangwan, Bhawana Mishra, Jyoti Singh Jadaun, Neelam Singh Sangwan
Withania somnifera (Ashwagandha) is considered as Rasayana in Indian systems of medicine. This study reports a novel transcriptome of W. somnifera berries, with high depth, quality and coverage. Assembled and annotated transcripts for nearly all genes related with the withanolide biosynthetic pathway was obtained. Tissue-wide gene expression analysis reflected almost similar definitions for terpenoid pathway in leaf, root and berry tissues with relatively higher abundance of transcripts linked with steroid, phenylpropanoid metabolism as well as flavonoid metabolism in berry The metabolome map generated from the data embodied transcripts from 143 metabolic pathways connected together and mediated collectively by about 1792 unique enzyme functions specific to berry, leaf and root tissues, respectively...
February 15, 2019: Physiologia Plantarum
https://read.qxmd.com/read/30766584/resistance-status-to-deltamethrin-pyrethroid-of-culex-pipiens-pipiens-diptera-culicidae-collected-from-three-districts-of-tunisia
#11
Ahmed Tabbabi, Jabeur Daaboub, Raja Ben Cheikh, Ali Laamari, Mohamed Feriani, Chokri Boubaker, Ibtissem Ben Jha, Hassen Ben Cheikh
Objectives: The aim of the present study was to determine the susceptibility status of Culex pipiens pipiens populations against deltamehtrin insecticide. Methods: Larvae of Culex pipiens pipiens were collected from three breeding places in Northern and Southern Tunisia between 2003 and 2005. Early third and late fourth instars were tested against deltamethrin pyrethroid insecticide. Cross-resistance with DDT resistance was evaluated in studied samples to estimate the role of target site insensitivity and two synergists including piperonyl butoxide (Pb) and S,S,S-tributyl phosphorotrithioate (DEF) were used to estimate the role of detoxification enzymes...
December 2018: African Health Sciences
https://read.qxmd.com/read/30734611/evaluation-of-the-impact-of-waterpipe-tobacco-smoke-exposure-on-the-activity-and-expression-of-rat-hepatic-cyp450-a-pharmacokinetic-study
#12
Osama Y Alshogran, Leen S Magarbeh, Karem H Alzoubi, Mohammad I Saleh, Omar F Khabour
Waterpipe smoke contains many toxic constituents that can alter drug pharmacokinetics. This study assessed the effect of waterpipe smoke exposure on the activity and expression of CYP450 enzymes in rats. Animals (n = 10/group) were exposed to either waterpipe smoke or side-stream cigarette smoke for 1 h/day (6 days/week) for 31 days, or fresh air (control). An intragastric cocktail solution containing three probe drugs, phenacetin, chlorzoxazone and testosterone was administered to assess the activity of CYP1A2, CYP2E1 and CYP3A, respectively...
February 8, 2019: Inhalation Toxicology
https://read.qxmd.com/read/30719367/polypharmacy-leading-to-priapism-in-hiv-patient-with-schizoaffective-disorder-a-cyp450-cascade
#13
Vinod Sharma, Aditi Sharma
With increasing trend of polypharmacy, there are higher chances of drug-drug interactions leading to adverse effects, especially in psychiatric patients with co-morbid chronic medical problems. This case demonstrates a schizoaffective 30-year-old male on highly active antiretroviral therapy (HAART) who reported an incident of priapism potentially caused by an interaction between previously prescribed atypical antipsychotic, trazodone, norepinephrine dopamine reuptake inhibitor (NDRI), HAART, and newly added selective serotonin reuptake inhibitor (SSRI)...
2019: Case Reports in Psychiatry
https://read.qxmd.com/read/30713251/mouse-pharmacokinetics-and-in-vitro-metabolism-of-%C3%A2-cremastranone
#14
Eun-Yeong Kim, Bit Lee, Seung-Yong Seo, Kiho Lee
The objective of this study was to characterize pharmacokinetics and metabolism of (±)-cremastranone (CMT) in mouse. Plasma concentrations of CMT following a single oral dose (10 mg/kg) were all below quantitation limit throughout 24-h time course, indicating poor oral bioavailability. Its plasma levels declined rapidly, with a half-life (t1/2 ) of 1.5 ± 0.3 min following a single intravenous dose (5 mg/kg). They were below the quantitation limit after 15 min post-dosing. CMT showed a high plasma clearance (CLp ) of 7...
2019: Biological & Pharmaceutical Bulletin
https://read.qxmd.com/read/30702301/fixed-dose-combination-formulations-multi-layered-platforms-designed-for-the-management-of-cardiovascular-disease
#15
Gavin P Andrews, Shu Li, Ammar Almajaan, Tao Yu, Luigi Martini, Anne Marie Healy, David S Jones
Hyperlipidaemia is considered as one of the main risk factors associated with cardiovascular diseases (CVDs). Among different lipid-lowering agents used to manage hyperlipidaemia, statins are highly prescribed for management of hyperlipidaemia with simvastatin being one of the most common. Simvastatin is susceptible to extensive metabolism by CYP450 3A4 and 3A5 which are expressed both in the liver and the gastrointestinal tract. Nevertheless, the localization of these enzymes is site dependent with lower concentration at the distal/proximal regions of the small intestine/colon...
January 31, 2019: Molecular Pharmaceutics
https://read.qxmd.com/read/30699381/evaluation-of-diclofenac-biodegradation-by-the-ascomycete-fungus-penicillium-oxalicum-at-flask-and-bench-bioreactor-scales
#16
Dario Rafael Olicón-Hernández, R Lucero Camacho-Morales, Clementina Pozo, Jesús González-López, Elisabet Aranda
Diclofenac (DFC) is a common anti-inflammatory drug, and has attracted the significant attention due to its massive use around the world and its environmental impact. In this work, we describe for the first time the use of Penicillium oxalicum, an ascomycetes fungus, for the biotransformation of DFC at flask and bench bioreactor scales. We present a complete study of the role of enzymes, metabolic pathway, acute toxicity assays and comparison between free and immobilised biomass. Pellets of P. oxalicum degraded 100 μM of DFC within 24 h, and the activity of CYP450 enzymes was key for the elimination of the drug...
January 22, 2019: Science of the Total Environment
https://read.qxmd.com/read/30690186/atipamezole-is-a-promising-non-discriminative-inhibitor-against-pan-cyp450-including-diclofenac-4-hydroxylation-a-comparison-with-abt-for-drug-adme-optimization-and-mechanism-study
#17
Zheng Li, Yunxia Zhang, You Gao, Yanan Xiang, Wenpeng Zhang, Chuang Lu, Xiaomei Zhuang
1-aminobenzotriazole (ABT) is a known P450 enzyme non-selective inactivator that serves as a tool for assessing P450-mediated metabolism. However, many findings demonstrated that ABT was ineffective with human CYP2C9. A profound pan-CYP450 inhibitor is desired avoid the risk of incomplete inhibition of P450, especially CYP2C9. Atipamezole is commonly used to recover animals from sedation-anesthesia induced by α2- adrenoceptor agonists. The purpose of this study is to evaluate atipamezole as a non-selective inhibitor of P450 enzymes and compare it with ABT...
January 25, 2019: European Journal of Pharmaceutical Sciences
https://read.qxmd.com/read/30654691/pharmacokinetics-behaviors-of-l-menthol-after-inhalation-and-intravenous-injection-in-rats-and-its-inhibition-effects-on-cyp450-enzymes-in-rat-liver-microsomes
#18
Xiuli Feng, Yan Liu, Xiao Sun, Ang Li, Xiaoyan Jiang, Xiaosong Zhu, Zhongxi Zhao
1. L-menthol, as a kind of monocyclic terpene, is widely used in inhalation formulations, food and tobacco. The purpose of this study was to investigate the pharmacokinetic behavior of l-menthol as well as its influence on the activities of cytochrome P450 enzymes. 2. The pharmacokinetic behaviors of l-menthol after inhalation (50 mg/kg) and intravenous injection (10 mg/kg) were investigated. A rat liver microsomal model was adopted to elucidate the inhibitory effect of l-menthol on CYP1A2, CYP2C11, CYP2D1/2, CYP2D4, CYP2E1, and CYP3A1 using phenacetin, tolbutamide, omeprazole, dextromethorphan, chlorzoxazone and testosterone as probe drugs, respectively...
January 18, 2019: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://read.qxmd.com/read/30634532/metabolic-activation-and-carcinogenesis-of-tobacco-specific-nitrosamine-n-nitrosonornicotine-nnn-a-density-function-theory-and-molecular-docking-study
#19
Tengjiao Fan, Guohui Sun, Lijiao Zhao, Xin Cui, Rugang Zhong
N'-nitrosonornicotine (NNN) is one of the tobacco-specific nitrosamines (TSNAs) that exists widely in smoke and smokeless tobacco products. NNN can induce tumors in various laboratory animal models and has been identified by International Agency for Research on Cancer (IARC) as a human carcinogen. Metabolic activation of NNN is primarily initiated by cytochrome P450 enzymes (CYP450s) via 2'-hydroxylation or 5'-hydroxylation. Subsequently, the hydroxylating intermediates undergo spontaneous decomposition to generate diazohydroxides, which can be further converted to alkyldiazonium ions, followed by attacking DNA to form various DNA damages, such as pyridyloxobutyl (POB)-DNA adducts and pyridyl-N-pyrrolidinyl (py-py)-DNA adducts...
January 9, 2019: International Journal of Environmental Research and Public Health
https://read.qxmd.com/read/30633984/aspergillus-flavus-link-toxins-reduces-the-fitness-of-dengue-vector-aedes-aegypti-linn-and-their-non-target-toxicity-against-aquatic-predator
#20
Prabhakaran Vasantha-Srinivasan, Sengodan Karthi, Muthiah Chellappandian, Athirstam Ponsankar, Annamalai Thanigaivel, Sengottayan Senthil-Nathan, Devarajan Chandramohan, Raja Ganesan
Mosquito that accountable for dispersal of dengue fever is Aedes aegypti Linn. and considered to be a chief vector for dengue especially in South Asian countries. Aspergillus flavus is considered to be wild growing green yellow colonies and synthesis highly regulating aflatoxins (B1, B2, G1 and G2) as a secondary metabolite. Mycotoxins of A. flavus showed its efficacy against III and IV instars of Ae. aegypti with more than 90% mortality at the prominent dosage of 2 × 108 conidia/ml. The proximate lethal concentrations (LC50 and LC90 ) of mycotoxins against third and fourth instars was 2 × 105 and 2 × 107 respectively...
January 8, 2019: Microbial Pathogenesis
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