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Cytochrome P-450

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https://www.readbyqxmd.com/read/29038839/hepatotoxic-combination-effects-of-three-azole-fungicides-in-a-broad-dose-range
#1
T Heise, F Schmidt, C Knebel, S Rieke, W Haider, I Geburek, L Niemann, P Marx-Stoelting
Single active substances of pesticides are thoroughly examined for their toxicity before approval. In this context, the liver is frequently found to be the main target organ. Since consumers are generally exposed to multiple residues of different active substances via the diet, it is important to analyse combinations of active substances for potential mixture effects. For the (tri-)azoles, a group of agricultural fungicides and antifungal drugs, combination effects on the liver are likely because of a similar mode of action...
October 16, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28992765/phenotyping-of-cyp-4501a2-activity-by-total-overnight-salivary-caffeine-assessment-tosca-in-patients-on-warfarin-treatment-a-cross-sectional-study
#2
Giovanni Tarantino, Domenico Capone, Paola Contaldi, Adriana Gianno, Mosca Teresa, Antonella Tufano
Warfarin is an oral anticoagulant, commonly used for primary and secondary prevention of venous and arterial thromboembolic events. The drug is characterized by narrow therapeutic index, widespread individual variability in clinical response, and high rates of adverse events, particularly bleeding complications. For these reasons, a close monitoring of the dosage, using the frequent assessment of coagulation status by means of International Normalized Ratio value, is mandatory. Warfarin is metabolized by hepatic cytochrome P-450...
January 1, 2017: Clinical and Applied Thrombosis/hemostasis
https://www.readbyqxmd.com/read/28986745/nutritional-and-metabolic-stressors-on-ovine-oocyte-development-and-granulosa-cell-functions-in-vitro
#3
S Nandi, S K Tripathi, P S P Gupta, S Mondal
The present study was undertaken to study the effect of ammonia, urea, non-esterified fatty acid (NEFA), and β-hydroxybutyric acid (β-OHB) on oocyte development and granulosa cell (GC) growth parameter of ovine (Ovis aries). Ovine oocytes were matured in vitro in the presence of different concentration of ammonia, urea, NEFA, and β-OHB for 24 h, in vitro inseminated and evaluated for cleavage and blastocyst yield. Same concentrations of ammonia, urea, NEFA, and β-OHB were examined on growth parameters and hormone secretion activity of granulosa cells in vitro...
October 6, 2017: Cell Stress & Chaperones
https://www.readbyqxmd.com/read/28962866/in-vitro-metabolism-of-4-5-dimethoxycanthin-6-one-by-human-liver-microsomes-and-its-inhibition-on-human-cyp1a2
#4
Xiaolei Miao, Jiaojiao You, Junjun Wang, Yong Chen
AIMS: P. quassioides is a traditional Chinese medicine used for the treatment of gastroenteritis, snakebite, infection and hypertension in China. 4, 5-dimethoxycanthin-6-one is one of the main active canthinone alkaloid isolated from P. quassioides. The aim of this work was to identify the cytochrome P (CYP) 450 enzymes responsible for the metabolism of 4, 5-dimethoxycanthin-6-one (DCO) and to evaluate the inhibitory effect of DCO on CYP activity in human liver microsomes (HLM) in vitro...
September 26, 2017: Life Sciences
https://www.readbyqxmd.com/read/28951593/microrna-regulation-of-cyp-1a2-cyp3a4-and-cyp2e1-expression-in-acetaminophen-toxicity
#5
Pritmohinder Gill, Sudeepa Bhattacharyya, Sandra McCullough, Lynda Letzig, Prasun J Mishra, Chunqiao Luo, Harsh Dweep, Laura James
MicroRNAs (miRNAs) that regulate the cytochrome P-450 isoforms involved in acetaminophen (APAP) toxicity were examined in HepaRG cells treated with APAP (20 mM). In-vitro studies found that APAP protein adducts were increased at 1 h, followed by ALT increases at 12 and 24 h. CYP1A2, CYP3A4 and CYP2E1 mRNA levels were decreased, while miRNAs were increased for miR-122-5p, miR-378a-5p, miR-27b-3p at 6 h and miR-125b-5p at 12 h and miR-27b-3p at 24 h. Putative miRNA binding sites on the 3'UTRs of the CYPs were identified in-silico...
September 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28945341/biocompatible-60-70-fullerenols-potent-defense-against-oxidative-injury-induced-by-reduplicative-chemotherapy
#6
Yue Zhou, Jie Li, Haijun Ma, Mingming Zhen, Jun Guo, Liping Wang, Li Jiang, Chunying Shu, Chunru Wang
Chemotherapy as a conventional cancer treatment suffers from critical systemic side effects, which is generally considered as the consequence of reactive oxygen species (ROS). Fullerenes have been widely studied for their excellent performance in radicals scavenging. In the present study, we report a solid-liquid reaction to synthesize fullerenols and their application as ROS scavengers in chemotherapy protection. The solid-liquid reaction is carried out without catalyst and suitable for mass production. The novel [60]/[70] fullerenols show a high stability in water, and the [70] fullerenols (C70-OH) exhibit radical scavenging capability superior to that of [60] fullerenols (C60-OH) in chemotherapy protection...
October 18, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28892923/atorvastatin-induced-adverse-drug-reactions-among-south-indian-tamils
#7
Chandrasekaran Indumathi, Natarajan Anusha, Kolar Vishwanath Vinod, Satheesh Santhosh, Steven Aibor Dkhar
INTRODUCTION: Atorvastatin is the most widely used statin world-over. Although atorvastatin is beneficial in reducing cardiovascular morbidity and mortality, they are associated with Adverse Drug Reactions (ADRs) which are under-recognized as well as under-reported. There is no data on safety of atorvastatin in ethnic populations like South Indian Tamils and hence the need for this study. AIM: To report the Adverse Events (AEs) associated with atorvastatin use, their causality and severity in dyslipidemic south Indian Tamils...
July 2017: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28780894/gene-therapy-for-hypertension
#8
Ludovit Paulis, Heinrich Franke, Fedor Simko
The control of hypertension and the resulting cardiovascular events is still insufficient. Thus, the search for novel means for blood pressure (BP) reduction remains worth further clinical and research attention. The advances in vector and construct design sketch the use of gene therapy in hypertension. Areas covered: We have searched for studies using gene therapy in hypertension reporting BP outcomes. We have identified 63 experimental studies demonstrating feasible targeting of the classical and new renin-angiotensin-aldosterone system, β1-adrenergic receptor, NO-cGMP axis, endothelin, natriuretic peptides, kallikrein system, cytochrome P-450 hydroxylase, oncogenes, growth factors, interleukins, angiopoietin-1, adrenomedullin or Klotho in small rodents...
August 17, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28780396/mobile-phone-1800mhz-radiation-impairs-female-reproduction-in-mice-mus-musculus-through-stress-induced-inhibition-of-ovarian-and-uterine-activity
#9
Saba Shahin, Surya Pal Singh, Chandra Mohini Chaturvedi
Present study investigated the long-term effects of mobile phone (1800MHz) radiation in stand-by, dialing and receiving modes on the female reproductive function (ovarian and uterine histo-architecture, and steroidogenesis) and stress responses (oxidative and nitrosative stress). We observed that mobile phone radiation induces significant elevation in ROS, NO, lipid peroxidation, total carbonyl content and serum corticosterone coupled with significant decrease in antioxidant enzymes in hypothalamus, ovary and uterus of mice...
August 2, 2017: Reproductive Toxicology
https://www.readbyqxmd.com/read/28744683/sources-and-toxicities-of-phenolic-polychlorinated-biphenyls-oh-pcbs
#10
Kiran Dhakal, Gopi S Gadupudi, Hans-Joachim Lehmler, Gabriele Ludewig, Michael W Duffel, Larry W Robertson
Polychlorinated biphenyls (PCBs), a group of 209 congeners that differ in the number and position of chlorines on the biphenyl ring, are anthropogenic chemicals that belong to the persistent organic pollutants (POPs). For many years, PCBs have been a topic of interest because of their biomagnification in the food chain and their environmental persistence. PCBs with fewer chlorine atoms, however, are less persistent and more susceptible to metabolic attack, giving rise to chemicals characterized by the addition of one or more hydroxyl groups to the chlorinated biphenyl skeleton, collectively known as hydroxylated PCBs (OH-PCBs)...
July 25, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/28744217/the-association-of-combined-gstm1-and-cyp2c9-genotype-status-with-the-occurrence-of-hemorrhagic-cystitis-in-pediatric-patients-receiving-myeloablative-conditioning-regimen-prior-to-allogeneic-hematopoietic-stem-cell-transplantation
#11
Chakradhara Rao S Uppugunduri, Flavia Storelli, Vid Mlakar, Patricia Huezo-Diaz Curtis, Aziz Rezgui, Yves Théorêt, Denis Marino, Fabienne Doffey-Lazeyras, Yves Chalandon, Peter Bader, Youssef Daali, Henrique Bittencourt, Maja Krajinovic, Marc Ansari
Hemorrhagic cystitis (HC) is one of the complications of busulfan-cyclophosphamide (BU-CY) conditioning regimen during allogeneic hematopoietic stem cell transplantation (HSCT) in children. Identifying children at high risk of developing HC in a HSCT setting could facilitate the evaluation and implementation of effective prophylactic measures. In this retrospective analysis genotyping of selected candidate gene variants was performed in 72 children and plasma Sulfolane (Su, water soluble metabolite of BU) levels were measured in 39 children following treatment with BU-CY regimen...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28731686/pyrethroid-insecticide-cypermethrin-accelerates-pubertal-onset-in-male-mice-via-disrupting-hypothalamic-pituitary-gonadal-axis
#12
Xiaoqing Ye, Feixue Li, Jianyun Zhang, Huihui Ma, Dapeng Ji, Xin Huang, Thomas E Curry, Weiping Liu, Jing Liu
Pyrethroids, a class of insecticides that are widely used worldwide, have been identified as endocrine-disrupting chemicals (EDCs). Our recent epidemiological study reported on an association of increased pyrethroids exposure with elevated gonadotropins levels and earlier pubertal development in Chinese boys. In this study, we further investigated the effects of cypermethrin (CP), one of the most ubiquitous pyrethroid insecticides, on hypothalamic-pituitary-gonadal (HPG) axis and pubertal onset in male animal models...
August 8, 2017: Environmental Science & Technology
https://www.readbyqxmd.com/read/28652425/evaluation-of-biological-activity-of-mastic-extracts-based-on-chemotherapeutic-indices
#13
Ryuichiro Suzuki, Hiroshi Sakagami, Shigeru Amano, Kunihiko Fukuchi, Katsuyoshi Sunaga, Taisei Kanamoto, Shigemi Terakubo, Hideki Nakashima, Yoshiaki Shirataki, Mineko Tomomura, Yoshiko Masuda, Satoshi Yokose, Akito Tomomura, Hirofumi Watanabe, Masaki Okawara, Yoshiharu Matahira
BACKGROUND: Most previous mastic investigators have not considered its potent cytotoxicity that may significantly affect the interpretation of obtained data. In the present study, we re-evaluated several biological activities of mastic extracts, based on chemotherapeutic indexes. MATERIALS AND METHODS: Pulverized mastic gum was extracted with n-hexane and then with ethyl acetate or independently with methanol or n-butanol. Tumor specificity (TS) of the extracts was determined by their cytotoxicity against human malignant and non-malignant cells...
July 2017: In Vivo
https://www.readbyqxmd.com/read/28628909/nonalcoholic-fatty-liver-disease-impairs-the-cytochrome-p-450-dependent-metabolism-of-%C3%AE-tocopherol-vitamin-e
#14
Desirée Bartolini, Pierangelo Torquato, Carolina Barola, Angelo Russo, Chiara Rychlicki, Danilo Giusepponi, Guido Bellezza, Angelo Sidoni, Roberta Galarini, Gianluca Svegliati-Baroni, Francesco Galli
This study aims to investigate in in vivo and in vitro models of nonalcoholic fatty liver disease (NAFLD) the enzymatic metabolism of α-tocopherol (vitamin E) and its relationship to vitamin E-responsive genes with key role in the lipid metabolism and detoxification of the liver. The experimental models included mice fed a high-fat diet combined or not with fructose (HFD+F) and HepG2 human hepatocarcinoma cells treated with the lipogenic agents palmitate, oleate or fructose. CYP4F2 protein, a cytochrome P-450 isoform with proposed α-tocopherol ω-hydroxylase activity, decreased in HFD and even more in HFD+F mice liver; this finding was associated with increased hepatic levels of α-tocopherol and decreased formation of the corresponding long-chain metabolites α-13-hydroxy and α-13-carboxy chromanols...
June 7, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28617523/electrochemical-characterization-of-geobacter-lovleyi-identifies-limitations-of-microbial-fuel-cell-performance-in-constructed-wetlands
#15
Clara Corbella, Rebecca P Steidl, Jaume Puigagut, Gemma Reguera
Power generation in microbial fuel cells implemented in constructed wetlands (CW-MFCs) is low despite the enrichment of anode electricigens most closely related to Geobacter lovleyi. Using the model representative G. lovleyi strain SZ, we show that acetate, but not formate or lactate, can be oxidized efficiently but growth is limited by the high sensitivity of the bacterium to oxygen. Acetate and highly reducing conditions also supported the growth of anode biofilms but only at optimal anode potentials (450 mV vs...
June 2017: International Microbiology: the Official Journal of the Spanish Society for Microbiology
https://www.readbyqxmd.com/read/28603032/%C3%AE-2-adrenergic-receptor-mediated-in-vitro-regulation-of-human-hepatic-drug-transporter-expression-by-epinephrine
#16
Abdullah Mayati, Amélie Moreau, Claire Denizot, Bruno Stieger, Yannick Parmentier, Olivier Fardel
The catecholamine epinephrine is known to repress expression of hepatic drug metabolizing enzymes such as cytochromes P-450. The present study was designed to determine whether epinephrine may also target expression of main hepatic drug transporters, that play a major role in liver detoxification and are commonly coordinately regulated with drug detoxifying enzymes. Treatment of primary human hepatocytes with 10μM epinephrine for 24h repressed mRNA expression of various transporters, such as the sinusoidal influx transporters NTCP, OATP1B1, OATP2B1, OAT2, OAT7 and OCT1 and the efflux transporters MRP2, MRP3 and BSEP, whereas it induced that of MDR1, but failed to alter that of BCRP...
August 30, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28571502/liver-toxicity-mechanisms-of-herbs-commonly-used-in-latin-america
#17
Sofía López-Gil, Natalia Nuño-Lámbarri, Norberto Chávez-Tapia, Misael Uribe, Varenka J Barbero-Becerra
Mexico owns approximately 4500 medicinal plants species, a great diversity that position it at the second place after China. According to the Mexican health department, 90% of common population consumes them to treat various diseases. Additionally, herbal remedies in Latin America (LA) are considered a common practice, but the frequency of use and the liver damage related to its consumption is still unknown. Despite the high prevalence and indiscriminate herbal consumption, the exact mechanism of hepatotoxicity and adverse effects is not fully clarified and is still questioned...
July 4, 2017: Drug Metabolism Reviews
https://www.readbyqxmd.com/read/28541669/effects-of-polychlorinated-biphenyls-pcbs-and-their-hydroxylated-metabolites-oh-pcbs-on-arabidopsis-thaliana
#18
Srishty Subramanian, Jerald L Schnoor, Benoit Van Aken
Plants metabolize polychlorinated biphenyls (PCBs) into hydroxylated derivatives (OH-PCBs), which are sometimes more toxic than the parent PCBs. The objective of this research was to compare the toxicity of a suite of PCBs and OH-PCBs toward the model plant, Arabidopsis thaliana. While parent PCBs and higher-chlorinated OH-PCBs exhibited a low or nondetectable toxicity, lower-chlorinated OH-PCBs significantly inhibited the germination rate and plant growth, with inhibition concentration 50% (IC50) ranging from 1...
June 20, 2017: Environmental Science & Technology
https://www.readbyqxmd.com/read/28513969/effect-of-steady-state-faldaprevir-on-pharmacokinetics-of-atorvastatin-or-rosuvastatin-in-healthy-volunteers-a-prospective-open-label-fixed-sequence-crossover-study
#19
Fenglei Huang, Kristell Marzin, Rüdiger Koenen, Klaus Peter Kammerer, Natalja Strelkowa, Mabrouk Elgadi, Anne-Marie Quinson, Sebastian Haertter
Faldaprevir (FDV) is a potent, orally administered inhibitor of hepatitis C virus protease. It inhibits multiple cytochrome P-450 enzymes and multiple membrane transporters. The objective of this study was to evaluate the effect of steady-state faldaprevir on the pharmacokinetics (PK) of a single dose of atorvastatin or rosuvastatin. In this single-center, open-label, fixed-sequence crossover study, 33 healthy adult male and female volunteers were given either atorvastatin 10 mg (n = 16) or rosuvastatin 10 mg (n = 17) on day 1...
May 17, 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28513222/the-contribution-of-cyp2c-gene-subfamily-involved-in-epoxygenase-pathway-of-arachidonic-acids-metabolism-to-hypertension-susceptibility-in-russian-population
#20
Alexey Polonikov, Marina Bykanova, Irina Ponomarenko, Svetlana Sirotina, Anna Bocharova, Kseniya Vagaytseva, Vadim Stepanov, Mikhail Churnosov, Olga Bushueva, Maria Solodilova, Yaroslav Shvetsov, Vladimir Ivanov
Numerous studies demonstrated an importance of cytochrome P-450 epoxygenase pathway of arachidonic acids metabolism for the pathogenesis of essential hypertension (EH). The present study was designed to investigate whether common single-nucleotide polymorphisms (SNP) of CYP2C gene subfamily such as CYP2C8 (rs7909236 and rs1934953), CYP2C9 (rs9332242), and CYP2C19 (rs4244285) are associated with susceptibility to EH in Russian population. A total of 816 unrelated Russian individuals comprising 425 EH patients and 391 normotensive controls were included into the study...
2017: Clinical and Experimental Hypertension: CHE
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