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https://www.readbyqxmd.com/read/28632894/flavonoids-as-modulators-of-metabolic-enzymes-and-drug-transporters
#1
REVIEW
Anca Miron, Ana Clara Aprotosoaie, Adriana Trifan, Jianbo Xiao
Flavonoids, natural compounds found in plants and in plant-derived foods and beverages, have been extensively studied with regard to their capacity to modulate metabolic enzymes and drug transporters. In vitro, flavonoids predominantly inhibit the major phase I drug-metabolizing enzyme CYP450 3A4 and the enzymes responsible for the bioactivation of procarcinogens (CYP1 enzymes) and upregulate the enzymes involved in carcinogen detoxification (UDP-glucuronosyltransferases, glutathione S-transferases (GSTs))...
June 20, 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/28627888/investigation-of-drug-induced-hepatotoxicity-and-its-remediation-pathway-with-reaction-based-fluorescent-probes
#2
Dan Cheng, Wang Xu, Lin Yuan, Xiao-Bing Zhang
Drug-induced liver injury (DILI) is considered a serious problem related to public health, due to its unpredictability and acute response. The level of peroxynitrite (ONOO-) generated in liver has long been regarded as a biomarker for the prediction and measurement of DILI. Herein we present two reaction based fluorescent probes (Naph-ONOO- and Rhod-ONOO-) for ONOO- through a novel and universally applicable mechanism: ONOO- mediated deprotection of -keto caged fluorophores. Among them, Rhod-ONOO- can selectively accumulate and react in mitochondria, one of the main sources of ONOO-, with a substantial lower nano-molar sensitivity of 43 nM...
June 19, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28612092/involvement-of-cytochrome-p450-in-cisplatin-treatment-implications-for-toxicity
#3
REVIEW
Júlia Coelho França Quintanilha, Vanessa Marcilio de Sousa, Marília Berlofa Visacri, Laís Sampaio Amaral, Roseane Maria Maia Santos, Tomás Zambrano, Luis Antonio Salazar, Patricia Moriel
PURPOSE: The aim of this study is to evaluate the relationship between the CYP450 enzyme family and cisplatin toxicity. METHODS: This article examined a collection of studies suggesting that CYP450 enzymes may influence cisplatin toxicity. We performed a narrative mini-review. RESULTS: The studies review showed that CYP450 enzymes have an important role in drug-induced hepatotoxicity and nephrotoxicity, mainly CYP2E1 and CYP4A11. The studies also suggested that the cisplatin and CYP2E1 interaction leads to the generation of reactive oxygen species (ROS) and other oxidants resulting in renal injury; and that ROS generated by both the use of cisplatin and by the CYP2E1 increases tissue damage, induces apoptosis, and causes liver failure...
June 13, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28611737/de-novo-biosynthesis-of-apigenin-luteolin-and-eriodictyol-in-the-actinomycete-streptomyces-albus-and-production-improvement-by-feeding-and-spore-conditioning
#4
Laura Marín, Ignacio Gutiérrez-Del-Río, Paula Yagüe, Ángel Manteca, Claudio J Villar, Felipe Lombó
Nutraceutical compounds as plant flavonoids play an important role in prevention and modulation of diverse heath conditions, as they exert interesting antifungal, antibacterial, antioxidant, and antitumor effects. They also possess anti-inflammatory activities in arthritis, cardiovascular disease or neurological diseases, as well as modulatory effects on the CYP450 activity on diverse drugs. Most flavonoids are bioactive molecules of plant origin, but their industrial production is sometimes hindered due to reasons as low concentration in the plant tissues, presence in only some species or as a complex mixture or inactive glycosides in plant vacuolae...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28603633/in-vitro-metabolism-of-exemestane-by-hepatic-cytochrome-p450s-impact-of-nonsynonymous-polymorphisms-on-formation-of-the-active-metabolite-17%C3%AE-dihydroexemestane
#5
Amity Peterson, Zuping Xia, Gang Chen, Philip Lazarus
Exemestane (EXE) is an endocrine therapy commonly used by postmenopausal women with hormone-responsive breast cancer due to its potency in inhibiting aromatase-catalyzed estrogen synthesis. Preliminary in vitro studies sought to identify phase I EXE metabolites and hepatic cytochrome P450s (CYP450s) that participate in EXE biotransformation. Phase I metabolites were identified by incubating EXE with HEK293-overexpressed CYP450s. CYP450s 1A2, 2C8, 2C9, 2C19, 2D6, 3A4, and 3A5 produce 17β-dihydroexemestane (17β-DHE), an active major metabolite, as well as two inactive metabolites...
June 2017: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/28601707/enhancement-of-biocompatibility-and-photoacoustic-contrast-activity-of-metal-clusters
#6
Arijit Bag, Pradip Kr Ghorai
Organometallic carbonyl clusters (OMCC) of group VIII elements are water soluble, bio-compatible and stable high-contrast photoacoustic agents for live cell imaging. But, they have limited application due to weak absorption within 700-1000nm wavelength which is known as the biological window of absorption. In this article, we report that hexa-nuclear iron (Fe6) carbonyl cluster derivatized with sodium thio-propanoate has very good absorption within 700-1600nm wave length. This modeled compound is water soluble and bio-compatible...
May 19, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/28594282/availability-of-cyp2d6-genotyping-results-in-general-practitioner-and-community-pharmacy-medical-records
#7
Mirjam Simoons, Hans Mulder, Robert A Schoevers, Henricus G Ruhé, Eric N van Roon
AIM: To investigate the availability of CYP450-2D6 (CYP2D6) genotyping results in general practitioner (GP) and/or community pharmacy records, and the influence thereof on psychotropic CYP2D6 substrate dosing. MATERIALS & METHODS: Primary outcome was the percentage of patients genotyped for CYP2D6 with their genotype/phenotype registered in GP and/or pharmacy records. Secondary outcome was the number of defined daily doses of psychotropic CYP2D6 substrates prescribed after genotyping...
June 8, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28592191/influence-of-two-variants-of-cyp450-oxidoreductase-on-the-stable-dose-of-acenocoumarol-in-a-spanish-population
#8
Hoi Y Tong, Alberto M Borobia, José Carlos Martínez Ávila, Rubin Lubomirov, Mario Muñoz, María J Blanco Bañares, Rafael Hernández, Carmen Fernández Capitán, Elena Ramírez, Jesús Frías, Antonio J Carcas
AIM: To evaluate the influence of two variants of P450 oxidoreductase (POR), rs2868177 and POR*28, on the stable dosage of acenocoumarol. PATIENTS & METHODS: For this observational, cross-sectional study, patients were undergone stable anticoagulant treatment with acenocoumarol. Univariate and multiple regression analyses were performed to assess the influence of POR polymorphisms. RESULTS: About 340 patients were enrolled. Multiple regression had a coefficient of determination (R(2)) of 51...
June 8, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28580548/development-of-an-eco-friendly-mosquitocidal-agent-from-alangium-salvifolium-against-the-dengue-vector-aedes-aegypti-and-its-biosafety-on-the-aquatic-predator
#9
Annamalai Thanigaivel, Prabhakaran Vasantha-Srinivasan, Edward-Sam Edwin, Athirstam Ponsankar, Selvaraj Selin-Rani, Muthiah Chellappandian, Kandaswamy Kalaivani, Sengottayan Senthil-Nathan, Giovanni Benelli
Plant extracts with their enriched chemical constituents have established potential alternative mosquito control agents. In this research, we developed an eco-friendly mosquitocidal agent from Alangium salvifolium leaves against the dengue and Zika virus vector Aedes aegypti and we investigated its biosafety on the mosquito aquatic predator Toxorhynchites splendens. Results showed that the methanolic extract of A. salvifolium leaves was composed by eight main compounds, with major peak area for hexadecenoic acid (21...
June 4, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/28555194/the-effects-of-formaldehyde-on-cytochrome-p450-isoform-activity-in-rats
#10
Min Xu, Huaqiao Tang, Qian Rong, Yuanli Zhang, Yinglun Li, Ling Zhao, Gang Ye, Fei Shi, Cheng Lv
Formaldehyde (FA) is an occupational and indoor pollutant. Long-term exposure to FA can irritate the respiratory mucosa, with potential carcinogenic effects on the airways. The effects of acute FA poisoning on the activities of CYP450 isoforms CYP1A2, CYP2C11, CYP2E1, and CYP3A2 were assessed by determining changes in the pharmacokinetic parameters of the probe drugs phenacetin, tolbutamide, chlorzoxazone, and testosterone, respectively. Rats were randomly divided into three groups: control, low FA dose (exposure to 110 ppm for 2 h for 3 days), and high FA dose (exposure to 220 ppm for 2 h for 3 days)...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28553308/identification-of-putative-genes-involved-in-limonoids-biosynthesis-in-citrus-by-comparative-transcriptomic-analysis
#11
Fusheng Wang, Mei Wang, Xiaona Liu, Yuanyuan Xu, Shiping Zhu, Wanxia Shen, Xiaochun Zhao
Limonoids produced by citrus are a group of highly bioactive secondary metabolites which provide health benefits for humans. Currently there is a lack of information derived from research on the genetic mechanisms controlling the biosynthesis of limonoids, which has limited the improvement of citrus for high production of limonoids. In this study, the transcriptome sequences of leaves, phloems and seeds of pummelo (Citrus grandis (L.) Osbeck) at different development stages with variances in limonoids contents were used for digital gene expression profiling analysis in order to identify the genes corresponding to the biosynthesis of limonoids...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28545313/effects-of-rosmarinic-acid-on-acetaminophen-induced-hepatotoxicity-in-male-wistar-rats
#12
Parisa Hasanein, Maryam Sharifi
CONTEXT: Drug-induced liver injury is a significant worldwide clinical problem. Rosmarinic acid (RA), a natural phenol, has antioxidant effects. OBJECTIVE: The effects of RA against acetaminophen (N-acetyl-p-amino-phenol (APAP))-induced oxidative damage and hepatotoxicity in rats were investigated. MATERIALS AND METHODS: Male Wistar rats were pretreated with RA (10, 50 and 100 mg/kg, i.g.) for one week. On day 7, rats received APAP (500 mg/kg, i...
December 2017: Pharmaceutical Biology
https://www.readbyqxmd.com/read/28545186/gallium-nanoparticle-mediated-reduction-of-brain-specific-serine-protease-4-in-an-experimental-metastatic-cancer-model
#13
Enas M Moustafa, Marwa Abdelhameed Mohamed, Noura M Thabet
Purpose: Tumor growth and metastasis depend on angiogenesis; therefore, efforts are being made to develop specific angiogenic inhibitors. Gallium (Ga) is the second most common metal ion, after platinum, used in cancer treatment. Its activities are numerous and various. In the present study, we aimed to investigate the effect of Ga on brain metastasis arising from hepatocellular carcinoma (HCC). Materials and methods: Forty experimental rats (divided into 4 groups) received diethylnitrosamine (DEN) at a dose (20 mg/kg...
April 1, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/28542812/modulating-nasal-mucosal-permeation-using-metabolic-saturation-and-enzyme-inhibition-techniques
#14
Varsha Dhamankar, Maureen D Donovan
OBJECTIVE: Presystemic elimination resulting from local enzymatic degradation can play a key role in limiting the bioavailability of intranasally administered drugs. The aim of this study was to evaluate the transfer of a metabolically susceptible drug across the nasal mucosa to illustrate the relative contributions of drug diffusivity and metabolic susceptibility on overall nasal mucosal permeation and to understand the effects of changes in enzymatic activity on the transfer across nasal epithelial and submucosal tissues...
May 23, 2017: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/28528513/the-expansive-role-of-oxylipins-on-platelet-biology
#15
REVIEW
Jennifer Yeung, Megan Hawley, Michael Holinstat
In mammals, three major oxygenases, cyclooxygenases (COXs), lipoxygenases (LOXs), and cytochrome P450 (CYP450), generate an assortment of unique lipid mediators (oxylipins) from polyunsaturated fatty acids (PUFAs) which exhibit pro- or anti-thrombotic activity. Over the years, novel oxylipins generated from the interplay of theoxygenase activity in various cells, such as the specialized pro-resolving mediators (SPMs), have been identified and investigated in inflammatory disease models. Although platelets have been implicated in inflammation, the role and mechanism of these SPMs produced from immune cells on platelet function are still unclear...
June 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/28524079/assembly-of-hepatocyte-spheroids-using-magnetic-3d-cell-culture-for-cyp450-inhibition-induction
#16
Pujan K Desai, Hubert Tseng, Glauco R Souza
There is a significant need for in vitro methods to study drug-induced liver injury that are rapid, reproducible, and scalable for existing high-throughput systems. However, traditional monolayer and suspension cultures of hepatocytes are difficult to handle and risk the loss of phenotype. Generally, three-dimensional (3D) cell culture platforms help recapitulate native liver tissue phenotype, but suffer from technical limitations for high-throughput screening, including scalability, speed, and handling. Here, we developed a novel assay for cytochrome P450 (CYP450) induction/inhibition using magnetic 3D cell culture that overcomes the limitations of other platforms by aggregating magnetized cells with magnetic forces...
May 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28506184/complications-of-psychotropic-and-pain-medications-in-an-ultrarapid-metabolizer-patient-at-the-upper-1-of-cytochrome-p450-cyp450-function-quantified-by-combinatorial-cyp450-genotyping
#17
Gualberto Ruaño, Karen Larsen, Mohan Kocherla, James Samuel Graydon, Jonathan Kost
A 44-year-old Caucasian woman presented with a history of empirical treatment with 20 pain and psychotropic medications, as well as dual comorbidity of intractable pain and depression. A multiple gain-of-function profile in the CYP450 family of cytochrome P450 (CYP450) drug metabolism isoenzymes was discovered. The patient was a homozygote of suprafunctional alleles for both CYP2D6 ((*)35/(*)35) and CYP2C19 ((*)17/(*)17) genes and functional alleles for CYP2C9 ((*)1/(*)1), which account for aggregate drug metabolism function at the upper 1% of the population...
June 2017: Journal of Pain & Palliative Care Pharmacotherapy
https://www.readbyqxmd.com/read/28494548/-the-role-of-cytochrome-p450-in-nonalcoholic-fatty-liver-induced-by-high-fat-diet-a-gene-expression-profile-analysis
#18
Y Liu, F Cheng, Y X Luo, P Hu, H Ren, M L Peng
Objective: To clarify the role of cytochrome P450 in nonalcoholic fatty liver disease (NAFLD) by RNA-Seq and bioinformatics analysis. Methods: A total of 20 male C57BL/6 mice were used. Ten mice were fed with high-fat diet (D12492, 60% kcal fat) for 16 weeks to establish a mouse model of NAFLD, and the other 10 mice were fed with low-fat diet (D12450B, 10% kcal fat) as control group. At the end of the experiment, the body weight, liver weight, and hepatic triglyceride (TG) content were measured. Meanwhile, HE staining and RNA-Seq analysis were performed for the liver tissues...
April 20, 2017: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
https://www.readbyqxmd.com/read/28486989/postnatal-treatment-using-curcumin-supplements-to-amend-the-damage-in-vpa-induced-rodent-models-of-autism
#19
Maha Al-Askar, Ramesa Shafi Bhat, Manar Selim, Laila Al-Ayadhi, Afaf El-Ansary
BACKGROUND: Valproic acid (VPA) is used as a first-line antiepileptic agent and is undergoing clinical trials for use as a treatment for many disorders. Mothers undergoing VPA treatment during early pregnancy reportedly show increased rates of autism among their offspring. The benefits of curcumin supplementation were investigated using an animal model of VPA-induced autism. METHODS: The study was performed using a rodent model of autism by exposing rat fetuses to valproic acid (VPA) on the 12...
May 10, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28473993/salvia-miltiorrhiza-roots-against-cardiovascular-disease-consideration-of-herb-drug-interactions
#20
REVIEW
Feng Chen, Li Li, Dan-Dan Tian
Salvia miltiorrhiza root (Danshen) is widely used in Asia for its cardiovascular benefits and contains both hydrophilic phenolic acids and lipophilic tanshinones, which are believed to be responsible for its therapeutic efficacy. This review summarized the effects of these bioactive components from S. miltiorrhiza roots on pharmacokinetics of comedicated drugs with mechanic insights regarding alterations of protein binding, enzyme activity, and transporter activity based on the published data stemming from both in vitro and in vivo human studies...
2017: BioMed Research International
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