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Cytochrome P450

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https://www.readbyqxmd.com/read/28737969/high-hydrostatic-pressure-extract-of-ginger-exerts-antistress-effects-in-immobilization-stressed-rats
#1
Sohee Moon, Mak-Soon Lee, Sunyoon Jung, Bori Kang, Seog-Young Kim, Seonyoung Park, Hye-Yeon Son, Chong-Tai Kim, Young-Hee Jo, In-Hwan Kim, Young Soon Kim, Yangha Kim
Stress contributes to physiological changes such as weight loss and hormonal imbalances. The aim of the present study was to investigate antistress effects of high hydrostatic pressure extract of ginger (HPG) in immobilization-stressed rats. Male Sprague-Dawley rats (n = 24) were divided into three groups as follows: control (C), immobilization stress (2 h daily, for 2 weeks) (S), and immobilization stress (2 h daily, for 2 weeks) plus oral administration of HPG (150 mg/kg body weight/day) (S+G). Immobilization stress reduced the body weight gain and thymus weight by 50...
July 24, 2017: Journal of Medicinal Food
https://www.readbyqxmd.com/read/28737724/time-dependent-inhibition-of-cyp2c8-and-cyp2c19-by-hedera-helix-extracts-a-traditional-respiratory-herbal-medicine
#2
Shaheed Ur Rehman, In Sook Kim, Min Sun Choi, Seung Hyun Kim, Yonghui Zhang, Hye Hyun Yoo
The extract of Hedera helix L. (Araliaceae), a well-known folk medicine, has been popularly used to treat respiratory problems, worldwide. It is very likely that this herbal extract is taken in combination with conventional drugs. The present study aimed to evaluate the effects of H. helix extract on cytochrome P450 (CYP) enzyme-mediated metabolism to predict the potential for herb-drug interactions. A cocktail probe assay was used to measure the inhibitory effect of CYP. H. helix extracts were incubated with pooled human liver microsomes or CYP isozymes with CYP-specific substrates, and the formation of specific metabolites was investigated to measure the inhibitory effects...
July 24, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28737453/the-metabolism-and-drug-drug-interaction-potential-of-the-selective-prostacyclin-receptor-agonist-selexipag
#3
Carmela Gnerre, Jérôme Segrestaa, Swen Seeland, Päivi Äänismaa, Thomas Pfeifer, Stephane Delahaye, Ruben de Kanter, Tomohiko Ichikawa, Tetsuhiro Yamada, Alexander Treiber
- The metabolism of selexipag has been studied in vivo in man and the main excreted metabolites were identified. Also, metabolites circulating in human plasma have been structurally identified and quantified. - The main metabolic pathway of selexipag in man is the formation of the active metabolite ACT-333679. Other metabolic pathways include oxidation and dealkylation reactions. All primary metabolites undergo subsequent hydrolysis of the sulphonamide moiety to their corresponding acids. ACT-333679 undergoes conjugation with glucuronic acid and aromatic hydroxylation to P10, the main metabolite detected in human faeces...
July 24, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/28736287/novel-approach-for-selective-reduction-of-nnn-in-cigarette-tobacco-filler-and-mainstream-smoke
#4
M Lusso, I Gunduz, A Kondylis, G Jaccard, L Ruffieux, F Gadani, K Lion, A Adams, W Morris, T Danielson, U Warek, J Strickland
Research conducted during past decades to reduce the level of the tobacco specific nitrosamine N-nitrosonornicotine (NNN) and its precursor nornicotine in tobacco yielded identification of three tobacco genes encoding for cytochrome P450 nicotine demethylases converting nicotine to nornicotine. We carried out trials to investigate the effect of using tobaccos containing three non-functional nicotine demethylase genes on the selective reduction of NNN in cigarette tobacco filler and mainstream smoke. Our results indicate that the presence of non-functional alleles of the three genes reduces the level of nornicotine and NNN in Burley tobacco by 70% compared to the level observed in currently available low converter (LC) Burley tobacco varieties...
July 20, 2017: Regulatory Toxicology and Pharmacology: RTP
https://www.readbyqxmd.com/read/28736226/rapid-effects-of-the-aromatase-inhibitor-fadrozole-on-steroid-production-and-gene-expression-in-the-ovary-of-female-fathead-minnows-pimephales-promelas
#5
Anthony L Schroeder, Gerald T Ankley, Tanwir Habib, Natalia Garcia-Reyero, Barbara L Escalon, Kathleen M Jensen, Michael D Kahl, Elizabeth J Durhan, Elizabeth A Makynen, Jenna E Cavallin, Dalma Martinovic-Weigelt, Edward J Perkins, Daniel L Villeneuve
Cytochrome P450 aromatase catalyzes conversion of C19 androgens to C18 estrogens and is critical for normal reproduction in female vertebrates. Fadrozole is a model aromatase inhibitor that has been shown to suppress estrogen production in the ovaries of fish. However, little is known about the early impacts of aromatase inhibition on steroid production and gene expression in fish. Adult female fathead minnows (Pimephales promelas) were exposed via water to 0, 5, or 50 µg fadrozole/L for a time-course of 0...
July 20, 2017: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/28736028/association-between-tacrolimus-pharmacokinetics-and-cytochrome-p450-3a5-and-multidrug-resistance-protein-1-exon-21-polymorphisms
#6
M Soda, M Fujitani, R Michiuchi, A Shibayama, K Kanamori, S Yoshikuni, Y Ohno, T Tsuchiya, A Suzuki, K Horie, T Deguchi, Y Itoh, K Kitaichi
BACKGROUND: Individual differences in the pharmacokinetics (PK) of tacrolimus (TAC), an immunosuppressive drug, are reportedly associated with single-nucleotide polymorphisms (SNPs) of cytochrome P450 (CYP) 3A5 and multidrug resistance protein 1 (MDR1). We determined the effect of SNPs in CYP3A5 and MDR1 exons 21 and 26 on TAC PK parameters. METHODS: Thirty-eight Japanese patients who underwent renal transplantation were genotyped for CYP3A5 and exons 21 and 26 of MDR1 with the use of polymerase chain reaction-restriction fragment length polymorphism analysis...
July 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28734978/insights-into-the-functional-properties-of-the-marneral-oxidase-cyp71a16-from-arabidopsis-thaliana
#7
Sarah Kranz-Finger, Osama Mahmoud, Esther Ricklefs, Nikolas Ditz, Patrick J Bakkes, Vlada B Urlacher
The Arabidopsis thaliana gene encoding CYP71A16 is part of the gene cluster for the biosynthesis and modification of the triterpenoid marneral. Previous investigations of A. thaliana have revealed that CYP71A16 oxidizes marneral, while it also can accept marnerol as substrate. The aim of the present study was to investigate functional properties of CYP71A16 in vitro. For this purpose, heterologous expression of a N-terminally modified version of CYP71A16 was established in Escherichia coli, which yielded up to 50mg·L(-1) recombinant enzyme...
July 19, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28734977/modulation-of-the-interaction-between-human-p450-3a4-and-b-megaterium-reductase-via-engineered-loops
#8
Silvia Castrignanò, Serena D'Avino, Giovanna Di Nardo, Gianluca Catucci, Sheila J Sadeghi, Gianfranco Gilardi
Chimerogenesis involving cytochromes P450 is a successful approach to generate catalytically self-sufficient enzymes. However, the connection between the different functional modules should allow a certain degree of flexibility in order to obtain functional and catalytically efficient proteins. We previously applied the molecular Lego approach to develop a chimeric P450 3A4 enzyme linked to the reductase domain of P450 BM3 (BMR). Three constructs were designed with the connecting loop containing no glycine, 3 glycine or 5 glycine residues and showed a different catalytic activity and coupling efficiency...
July 19, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28734960/pharmacokinetic-interactions-of-curcuminoids-with-conventional-drugs-a-review
#9
REVIEW
Roodabeh Bahramsoltani, Roja Rahimi, Mohammad Hosein Farzaei
ETHNOPHARMACOLOGICAL RELEVANCE: Herb-drug interactions are of great concern in health practices. Curcumin is a natural polyphenol extracted from turmeric, a spice widely used all over the world. Curcumin is clinically used due to its acceptable safety profile and therapeutic efficacy. AIM OF THE STUDY: Current paper aims to highlight the effect of curcumin on concomitantly used drugs. METHODS: Electronic databases including PubMed, Scopus and Science Direct were searched with the keywords "curcumin" in the title/abstract and "drug interaction," "drug metabolism," "cytochrome," "P-glycoprotein" and "P450" in the whole text...
July 19, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28734877/enzymatic-and-free-radical-formation-of-cis-and-trans-epoxyeicosatrienoic-acids-in-vitro-and-in-vivo
#10
Theresa Aliwarga, Brianne S Raccor, Rozenn N Lemaitre, Nona Sotoodehnia, Sina A Gharib, Libin Xu, Rheem A Totah
Epoxyeicosatrienoic acids (EETs) are metabolites of arachidonic acid (AA) oxidation that have important cardioprotective and signaling properties. AA is an ω -6 polyunsaturated fatty acid (PUFA) that is prone to autoxidation. Although hydroperoxides and isoprostanes are major autoxidation products of AA, EETs are also formed from the largely overlooked peroxyl radical addition mechanism. While autoxidation yields both cis- and trans-EETs, cytochrome P450 (CYP) epoxygenases have been shown to exclusively catalyze the formation of all regioisomer cis-EETs, on each of the double bonds...
July 19, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28732807/pharmacology-and-toxicology-of-%C3%AE-and-%C3%AE-asarone-a-review-of-preclinical-evidence
#11
REVIEW
Ranjithkumar Chellian, Vijayapandi Pandy, Zahurin Mohamed
BACKGROUND: Asarone is one of the most researched phytochemicals and is mainly present in the Acorus species and Guatteria gaumeri Greenman. In preclinical studies, both α- and β-asarone have been reported to have numerous pharmacological activities and at the same time, many studies have also revealed the toxicity of α- and β-asarone. PURPOSE: The purpose of this comprehensive review is to compile and analyze the information related to the pharmacokinetic, pharmacological, and toxicological studies reported on α- and β-asarone using preclinical in vitro and in vivo models...
August 15, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/28731962/polymorphisms-in-cytochrome-p450-oxidoreductase-and-its-effect-on-drug-metabolism-and-efficacy
#12
Liang Gong, Cong-Min Zhang, Jin-Feng Lv, Hong-Hao Zhou, Lan Fan
Cytochrome P450 oxidoreductase (POR) has played a potential role in the metabolism of drugs and steroids by supplying electrons to microsomal cytochrome P450 (CYP) enzymes. More than 200 different POR mutations and polymorphisms causing more than 130 amino acid changes in the POR protein have been reported since 2004. A503V is a common amino acid sequence variant encoded by POR*28, whereas A287P and R457H are the most common disease-causing mutations in Europeans and Asians, respectively. Polymorphisms in the POR gene can affect POR activity, CYP-mediated drug metabolism activities, and the efficacy of several clinically used drugs...
July 20, 2017: Pharmacogenetics and Genomics
https://www.readbyqxmd.com/read/28731262/nephroprotective-effects-of-anthocyanin-from-the-fruits-of-panax-ginseng-gfa-on-cisplatin-induced-acute-kidney-injury-in-mice
#13
Zhen-Lan Qi, Zi Wang, Wei Li, Jin-Gang Hou, Ying Liu, Xin-Dian Li, Hui-Ping Li, Ying-Ping Wang
Cisplatin is an effective anticancer chemotherapeutic agent, but the use of cisplatin in the clinic is severely limited by side effects. Nephrotoxicity is a major factor that contributes to the side effects of cisplatin chemotherapy. The aim of this research was to survey the nephroprotective effects of anthocyanin from the fruits of Panax ginseng (GFA) in a murine model of cisplatin-induced acute kidney injury. We observed that pretreatment with GFA attenuated cisplatin-induced elevations in blood urea nitrogen and creatinine levels and histopathological injury induced by cisplatin...
July 21, 2017: Phytotherapy Research: PTR
https://www.readbyqxmd.com/read/28730856/in-vitro-drug-drug-interactions-of-budesonide-inhibition-and-induction-of-transporters-and-cytochrome-p450-enzymes
#14
Nancy Chen, Donghui Cui, Qing Wang, Zhiming Wen, Richard D Finkelman, Devin Welty
1. Budesonide is a glucocorticoid used in the treatment of several respiratory and gastrointestinal inflammatory diseases. Glucocorticoids have been demonstrated to induce cytochrome P450 (CYP) 3A and the efflux transporter P-glycoprotein (P-gp). This study aimed to evaluate the potential of budesonide to act as a perpetrator or a victim of transporter- or CYP-mediated drug-drug interactions (DDIs). 2. In vitro studies were conducted for P-gp, breast cancer resistance protein and organic anion and cation transporters (OATP1B1, OATP1B3, OAT1, OAT3, OCT2) in transporter-transfected cells...
July 21, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/28730412/gns4-a-novel-allele-of-dwarf11-regulates-grain-number-and-grain-size-in-a-high-yield-rice-variety
#15
Yong Zhou, Yajun Tao, Jinyan Zhu, Jun Miao, Jun Liu, Yanhua Liu, Chuandeng Yi, Zefeng Yang, Zhiyun Gong, Guohua Liang
BACKGROUND: Rice plays an extremely important role in food safety because it feeds more than half of the world's population. Rice grain yield depends on biomass and the harvest index. An important strategy to break through the rice grain yield ceiling is to increase the biological yield. Therefore, genes associated with organ size are important targets for rice breeding. RESULTS: We characterized a rice mutant gns4 (grain number and size on chromosome 4) with reduced organ size, fewer grains per panicle, and smaller grains compared with those of WT...
December 2017: Rice
https://www.readbyqxmd.com/read/28730410/engineering-of-the-cytochrome-p450-monooxygenase-system-for-benzyl-maltol-hydroxylation
#16
Iori Kozono, Kousuke Mihara, Kazuyuki Minagawa, Makoto Hibi, Jun Ogawa
Maltol derivatives are utilized in a variety of fields due to their metal-chelating abilities, and modification of the 2-methyl side chain is known to effectively expand their functional diversity. In the present study, microbial enzymes were screened for hydroxylating activity towards the 2-methyl group in a maltol derivative, 3-benzyloxy-2-methyl-4-pyrone (BMAL). Novosphingobium sp. SB32149 was found to have the ability to convert BMAL into 3-benzyloxy-2-hydroxymethyl-4-pyrone (BMAL-OH). The enzymes responsible, a cytochrome P450 monooxygenase (P450nov), a ferredoxin (FDXnov), and a ferredoxin reductase (FDRnov), were identified in the SB32149 strain...
July 20, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28726984/physiology-and-endocrinology-symposium-alterations-in-uteroplacental-hemodynamics-during-melatonin-supplementation-in-sheep-and-cattle
#17
C O Lemley, K A Vonnahme
Compromised placental function can result in fetal growth restriction which is associated with greater risk of neonatal morbidity and mortality. Large increases in transplacental nutrient and waste exchange, which support the exponential increase in fetal growth during the last half of gestation, are dependent primarily on the rapid growth and vascularization of the uteroplacenta. The amplitude of melatonin secretion has been associated with improved oxidative status and altered cardiovascular function in several mammalian species; however, melatonin mediated alterations of uteroplacental capacity in sheep and cattle are lacking...
May 2017: Journal of Animal Science
https://www.readbyqxmd.com/read/28726718/inhibitory-effects-of-trapping-agents-of-sulfur-drug-reactive-intermediates-against-major-human-cytochrome-p450-isoforms
#18
Jasleen K Sodhi, Erlie Marie Delarosa, Jason S Halladay, James P Driscoll, Teresa Mulder, Patrick M Dansette, S Cyrus Khojasteh
In some cases, the formation of reactive species from the metabolism of xenobiotics has been linked to toxicity and therefore it is imperative to detect potential bioactivation for candidate drugs during drug discovery. Reactive species can covalently bind to trapping agents in in vitro incubations of compound with human liver microsomes (HLM) fortified with β-nicotinamide adenine dinucleotide phosphate (NADPH), resulting in a stable conjugate of trapping agent and reactive species, thereby facilitating analytical detection and providing evidence of short-lived reactive metabolites...
July 20, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28725042/global-deregulation-of-ginseng-products-may-be-a-safety-hazard-to-warfarin-takers-solid-evidence-of-ginseng-warfarin-interaction
#19
Haiyan Dong, Ji Ma, Tao Li, Yingying Xiao, Ning Zheng, Jian Liu, Yu Gao, Jingwei Shao, Lee Jia
Recent global deregulation of ginseng as the table food raises our concern about the possible ginseng-warfarin interaction that could be life-threatening to patients who take warfarin for preventing fatal strokes and thromboembolism while using ginseng products for bioenergy recovery. Here we show that quality-control ginsenosides, extracted from ginseng and containing its major active ingredients, produce dose- and time-dependent antagonism in rats against warfarin's anti-coagulation assessed by INR and rat thrombosis model...
July 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28725025/an-atypical-case-of-spg56-cyp2u1-related-spastic-paraplegia-presenting-with-delayed-myelination
#20
Gaku Minase, Satoko Miyatake, Shin Nabatame, Hiroshi Arai, Eriko Koshimizu, Takeshi Mizuguchi, Mitsuko Nakashima, Noriko Miyake, Hirotomo Saitsu, Toshinobu Miyamoto, Kazuo Sengoku, Naomichi Matsumoto
Hereditary spastic paraplegia (HSP) is a neurological disorder characterized by a progressive spasticity and muscle weakness of the lower limbs. It is divided into two subtypes, uncomplicated and complicated forms. Biallelic mutations in the cytochrome P450 2U1 gene (CYP2U1) are associated with spastic paraplegia type 56 (SPG56), manifesting both uncomplicated and complicated HSP. Accompanying clinical features include intellectual disability, dystonia, cerebellar ataxia, subclinical peripheral neuropathy, visual impairment, as well as abnormalities in brain magnetic resonance imaging...
July 20, 2017: Journal of Human Genetics
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