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CYP450 enzymes

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https://www.readbyqxmd.com/read/30311401/role-of-betaine-in-liver-injury-induced-by-the-exposure-to-ionizing-radiation
#1
Shereen M Shedid, Nadia Abdel-Magied, Helen N Saada
Oxidative stress, apoptosis, and fibrosis may play a major role in the development of radiation-induced liver damage. Betaine, a native compound widely present in beetroot, was reported to possess hepato-protective properties. The objective of this study was to investigate the influence of betaine on radiation-induced liver damage. Animals were exposed to 9 Gy applied in 3 doses of 3 Gy/wk. Betaine (400 mg/kg/d), was orally supplemented to rats after the first radiation dose, and daily during the irradiation period...
October 11, 2018: Environmental Toxicology
https://www.readbyqxmd.com/read/30308298/atrazine-exposure-triggers-common-carp-neutrophil-apoptosis-via-the-cyp450s-ros-pathway
#2
Shengchen Wang, Qiaojian Zhang, Shufang Zheng, Menghao Chen, Fuqing Zhao, Shiwen Xu
Due to the excessive pursuit of crop yields and the abuse of herbicides, water pollution caused by atrazine (ATR) has become one of the most severe environmental issues threatening the health of fish and aquatic animals. However, no detailed report has been conducted on the mechanisms of ATR immunotoxicity in fish neutrophils. To investigate these mechanism, we exposed peripheral blood neutrophils to 25 μg/ml atrazine for 1, 2, and 3 h. The results showed that ATR induced the mRNA expression of CYPs enzymes (CYP1A1, CYP1B1, CYP1C and CYP3A138), which increased the ROS levels, and inhibited the SOD and CAT activities, GSH content and spurred the accumulation of MDA...
October 8, 2018: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/30306496/effect-of-95-ethanol-khat-extract-and-cathinone-on-in-vitro-human-recombinant-cytochrome-p450-cyp-2c9-cyp2d6-and-cyp3a4-activity
#3
Sharoen Yu Ming Lim, Athira Rafhana Binti Azidin, Yee Tze Ung, Mustafa Al-Shagga, Mohammed Abdullah Alshawsh, Zahurin Mohamed, Chin Eng Ong, Yan Pan
BACKGROUND AND OBJECTIVE: A significant number of people worldwide consume khat on daily basis. Long term of khat chewing has shown negative impact on several organ systems. It is likely that these people are co-administered khat preparations and conventional medication, which may lead to khat-drug interactions. This study aimed to reveal the inhibitory potencies of khat ethanol extract (KEE) and its major active ingredient (cathinone) on human cytochrome P450 (CYP) 2C9, CYP2D6, and CYP3A4 enzymes activities, which are collectively responsible for metabolizing 70-80% clinically used drugs...
October 10, 2018: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/30288071/alterations-in-the-gene-expression-of-drug-and-arachidonic-acid-metabolizing-cyp450-in-the-livers-of-controlled-and-uncontrolled-insulin-dependent-diabetic-mice
#4
Yazun Bashir Jarrar, Luay Al-Essa, Abdulhasib Kilani, Mariam Hasan, Walid Al-Qerem
Background: Diabetic patients have lower capacity to metabolize drugs in comparison to normal people. Therefore, the present study aimed to investigate the alterations in gene expression of drug and arachidonic acid metabolizing cytochrome p450s (cyp450s) in the livers of controlled (CDM) and uncontrolled (UDM) insulin-dependent diabetic mice. Methods: Balb/c mice were treated with single dose of streptozocin (240 mg/kg) to induce diabetes and compared with control group, which was treated with citric buffer (pH =4...
2018: Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy
https://www.readbyqxmd.com/read/30268044/a-cytochrome-p450-monooxygenase-responsible-for-the-c-22-hydroxylation-step-in-the-paris-polyphylla-steroidal-saponin-biosynthesis-pathway
#5
Yan Yin, Linhui Gao, Xianan Zhang, Wei Gao
Polyphyllins are the major steroidal saponin components of Paris polyphylla, the main source plant of the common Chinese herbal medicine Paridis Rhizoma with strong pharmacological activity and extremely high economic value and great market prospects. However, the production of polyphyllins in plants is limited, and their biosynthesis pathway has not been reported. The downstream hydroxylation step was particularly unclear. To clarify the enzymes and intermediates involved in the downstream steps of polyphyllin biosynthesis, we performed a comparative transcriptome analysis and discovered a cytochrome P450 gene that encodes a protein with monooxygenase activity...
September 26, 2018: Phytochemistry
https://www.readbyqxmd.com/read/30253212/in-vitro-effect-of-mpeg-2k-pcl-x-micelles-on-rat-liver-cytochrome-p450-enzymes
#6
Lihui Qiu, Qian Li, Jiangeng Huang, Qi Wu, Kun Tu, Ya Wu, Xin Zhang, Junyi Qian, Ran Zhang, Gao Li, Minghui Sun, Luqin Si
The present study was aimed to evaluate the effects of amphiphilic copolymer micelles on six major hepatic cytochrome P450 (CYP) isoforms. A series of mPEG2k -PCLx polymeric micelles (mPEG2k -PCL2k , mPEG2k -PCL3.5k , mPEG2k -PCL5k and mPEG2k -PCL10k ) ranging from 20 to 100 nm were prepared to investigate the inhibitory or inductive activities by in vitro incubations of rat liver microsomes and primary rat hepatocytes. Inhibition of these polymeric micelles on CYP1A2, CYP2B1, CYP2C6, CYP2C11, CYP2D2 and CYP3A1/2 isoenzymes were observed above their critical micelle concentrations (>10 μg·mL-1 ) and in a concentration-dependent manner...
September 22, 2018: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/30233359/potential-metabolic-drug-drug-interaction-of-citrus-aurantium-l-rutaceae-evaluating-by-its-effect-on-3-cyp450
#7
Lu Zhou, Man Cui, Linlin Zhao, Dongsheng Wang, Tao Tang, Wenbo Wang, Sheng Wang, Huiyong Huang, Xinjian Qiu
Aim: Fructus aurantii (FA) is widely used in clinic as an expectorant and digestant herb in traditional Chinese medicine and proven to have a variety of pharmacological functions. FA is close to grapefruit either by botanical taxonomy or by their same components (flavonoids, etc.) and grapefruit has been proven to cause drug-drug interaction when co-administrated with CYP3A4 substrates. Besides, FA contains many compounds, such as flavonoids, which have been reported to impact the expressions of CYP450. However, the effect of FA on CYP450, whose change may affect drug safety and clinical efficacy attributed to drug-drug interaction, still remains unknown...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/30219678/metabolism-of-liver-cyp450-and-ultrastructural-changes-after-long-term-administration-of-aspirin-and-ibuprofen
#8
Congcong Wen, Zaishou Zhuang, Huanchun Song, Shuhua Tong, Xianchuan Wang, Yijing Lin, Haichao Zhan, Zhibin Chen, Lufeng Hu
Worldwide, aspirin and ibuprofen are the most commonly used non-steroidal anti-inflammatory drugs (NSAIDs). Some adverse reactions, including gastrointestinal reactions, have been concerned extensively. Nevertheless, the mechanism of liver injury remains unclear. In the present study, we focused on the metabolism of liver cytochrome P450 (CYP450) and ultrastructural morphology of liver cells. A total of thirty rats were divided into three groups of 10. Rats in the aspirin and ibuprofen groups were given enteric-coated aspirin (15 mg/kg) and ibuprofen (15 mg/kg), respectively by gavage for four weeks...
September 13, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/30218550/effect-of-glucocorticoids-on-androgen-biosynthesis-in-the-testes-of-the-toad-rhinella-arenarum-amphibia-anura
#9
Silvia Cristina Czuchlej, María Clara Volonteri, Eleonora Regueira, Nora Raquel Ceballos
In rat Leydig cells, glucocorticoids (GCs) inhibit testosterone production through the interaction with the glucocorticoid receptor (GR). However, the sensitivity of those cells to GCs is regulated by the enzyme 11β-hydroxysteroid dehydrogenase Type 1 (11β-HSD1). In the testes of the toad Rhinella arenarum, the presence of an 11β-HSD similar to type 2 and a cytosolic GR has also been described. However, there is a lack of information regarding the effects of GCs on amphibian testicular steroidogenesis. In this study, the effects of corticosterone on androgen production, and the activity of two steroidogenic enzymes in toad testes were reported...
September 15, 2018: Journal of Experimental Zoology. Part A, Ecological and Integrative Physiology
https://www.readbyqxmd.com/read/30215338/hepatic-flavin-containing-monooxygenase-and-aldehyde-oxidase-activities-in-male-domestic-pigs-at-different-ages
#10
Steven X Hu
BACKGROUND: Age has significant impact on activities of hepatic metabolizing enzymes in humans and animals. Flavin-containing monooxygenase (FMO) and aldehyde oxidase are two important hepatic enzymes. Understanding of impact of age on these two enzymes is still limited. This work was to investigate growth impact on hepatic FMO and AO activities in domestic male pigs. METHODS: Porcine liver microsomes and cytosol were prepared from the livers of male domestic pigs at ages of 1 day, 2, 5, 10 and 20 weeks...
September 13, 2018: Drug Metabolism Letters
https://www.readbyqxmd.com/read/30198716/near-infrared-photoactivatable-nitric-oxide-donors-with-integrated-photoacoustic-monitoring
#11
Effie Y Zhou, Hailey J Knox, Christopher J Reinhardt, Gina Partipilo, Mark J Nilges, Jefferson Chan
Photoacoustic (PA) tomography is a noninvasive technology that utilizes near-infrared (NIR) excitation and ultrasonic detection to image biological tissue at centimeter depths. While several activatable small-molecule PA sensors have been developed for various analytes, the use of PA molecules for deep-tissue analyte delivery and monitoring remains an underexplored area of research. Herein, we describe the synthesis, characterization, and in vivo validation of photoNOD-1 and photoNOD-2, the first organic, NIR-photocontrolled nitric oxide (NO) donors that incorporate a PA readout of analyte release...
September 19, 2018: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/30188556/fundamental-concepts-of-azole-compounds-and-triazole-antifungals-a-beginner-s-review
#12
REVIEW
Nelson Martínez-Matías, José R Rodríguez-Medina
Azoles are the most widely used drugs in antifungal therapy. They have a wide spectrum of activity against pathogenic fungi that are clinically relevant. However, they have been associated with adverse reactions and toxicity, both of which can be significant in patients. Compared to diazoles, triazoles discriminate better between their intended molecular target, the fungal CYP51 enzyme, and several enzymes of the human CYP450 system. Over the years, this superior discrimination has led to the favoring of triazoles over diazoles in the treatment of systemic mycoses...
September 2018: Puerto Rico Health Sciences Journal
https://www.readbyqxmd.com/read/30129421/genetic-polymorphisms-of-cytochrome-p450-2c9-enzyme-in-patients-with-type-2-diabetes-mellitus-in-turkmen-and-fars-ethnic-groups
#13
Mina Rabiee, Abdoljalal Marjani, Safoura Khajeniazi, Mohammad Mojerloo
BACKGROUND: Cytochrome P450 2C9 (CYP450 2C9) has an important role in metabolic processes. Mutations in CYP450 2C9 genes may affect the catalytic activity of this enzyme. The aim of the present study is to assess the genetic polymorphisms of Cytochrome P450 (2C9) enzyme in Turkmen and Fars ethnic groups with type 2 diabetes compared with controls. METHODS: A total of 336 Turkmen and 336 Fars type 2 diabetic patients and 336 healthy Turkmen and Fars individuals were included in this study...
August 21, 2018: Endocrine, Metabolic & Immune Disorders Drug Targets
https://www.readbyqxmd.com/read/30119852/a-novel-integrated-action-crossing-method-for-drug-drug-interaction-prediction-in-non-communicable-diseases
#14
Sathien Hunta, Thongchai Yooyativong, Nattapol Aunsri
BACKGROUND AND OBJECTIVE: Drug-drug interaction (DDI) is one of the main causes of toxicity and treatment inefficacy. This work focuses on non-communicable diseases (NCDs), the non-transmissible and long-lasting diseases since they are the leading cause of death globally. Drugs that are used in NCDs increase the probability of DDIs as a result of long time usage. This work proposes an Integrated Action Crossing (IAC) method that is effective in predicting the NCDs DDIs based on pharmacokinetic (PK) mechanism...
September 2018: Computer Methods and Programs in Biomedicine
https://www.readbyqxmd.com/read/30117405/in-vitro-drug-drug-interaction-potential-of-sulfoxide-and-or-sulfone-metabolites-of-albendazole-triclabendazole-aldicarb-methiocarb-montelukast-and-ziprasidone
#15
Poonam Giri, Lakshmikant Gupta, Sneha Naidu, Vipul Joshi, Nirmal Patel, Shyamkumar Giri, Nuggehally R Srinivas
BACKGROUND: The use of poly-pharmacy in the present day clinical therapy has made identification of clinical drug-drug interaction risk an important aspect of drug development process. Although many drugs can be metabolized to sulfoxide and/or sulfone metabolites, seldom is known on the CYP inhibition potential and/or the metabolic fate for such metabolites. OBJECTIVE: The key objectives were: a) to evaluate the in vitro CYP inhibition potential of select parent drugs with sulfoxide/sulfone metabolites; b) to assess the in vitro metabolic fate of the same panel of parent drugs and metabolites...
August 16, 2018: Drug Metabolism Letters
https://www.readbyqxmd.com/read/30115643/microfluidic-cell-culture-platforms-to-capture-hepatic-physiology-and-complex-cellular-interactions
#16
Shyam Sundhar Bale, Jeffrey T Borenstein
Animal models such as rats and primates provide body-wide information for drug and metabolite responses, including organ-specific toxicity and any unforeseen side effects on other organs. While effective in the drug screening process, their translatability to humans is limited due to the lack of high concordance and correlation between enzymatic mechanisms, cellular mechanisms and resulting toxicities. A significant mode of failure for safety prediction in drug screening is hepatotoxicity, resulting in ~30% of all safety-related drug failures and withdrawals from the market...
August 16, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/30114747/the-silk-gland-damage-and-the-transcriptional-response-to-detoxifying-enzymes-related-genes-of-bombyx-mori-under-phoxim-exposure
#17
Xiaoyu Cheng, Jiahuan Hu, Jinxin Li, Jian Chen, Hui Wang, Tingting Mao, Bin Xue, Bing Li
Silk gland is a major organ of Bombyx mori for the synthesis and secretion of silk protein. Phoxim exposure can be toxic to B. mori and causes a decrease of fibroin synthesis, finally affecting the silk production in industry. To study the mechanism of metabolism and detoxification of silk gland under phoxim exposure, we measured the residual quantity of phoxim in silk gland and hemolymph after phoxim exposure, and the detoxifying enzymes-related genes and enzyme activity were also investigated. Results indicated that the residual amount of phoxim existed up to 24 h in silk gland compared with that in hemolymph, suggesting that phoxim can accumulate in the silk glands within a certain time course...
October 2018: Chemosphere
https://www.readbyqxmd.com/read/30105921/clinical-implications-of-selective-serotonin-reuptake-inhibitors-selective-serotonin-norepinephrine-reuptake-inhibitors-pharmacogenetics-during-pregnancy-and-lactation
#18
Gideon Koren, Asher Ornoy
Depression occurs during pregnancy in 3.9-12.8% of the women. The different serotonin reuptake inhibitors (SRIs) are metabolized in the liver by CYP450 enzymes. CYP2D6 metabolizes paroxetine, fluoxetine, duloxetine and venlafaxine, while CYP2C19 deactivates citalopram and escitalopram. Polymorphisms in these enzymes change the metabolic clearance and levels of these drugs. Higher metabolism of most SRIs in late pregnancy results in lower maternal levels, which could result in decreased efficacy. Very few studies have addressed the potential interaction between pregnancy-induced increase in 2D6 metabolism and specific genotypes of the women, suggesting that ultra-rapid and extensive metabolizers exhibit lower serum concentrations than the other slower genotypes...
September 1, 2018: Pharmacogenomics
https://www.readbyqxmd.com/read/30100346/effects-and-mechanisms-of-sub-chronic-exposure-to-copper-nanoparticles-on-renal-cytochrome-p450-enzymes-in-rats
#19
Min Xu, Huaqiao Tang, XueRong Zhou, Helin Chen, Qi Dong, Yuanli Zhang, Gang Ye, Fei Shi, Cheng Lv, Bo Jing, Changliang He, Ling Zhao, Yinglun Li
Copper nanoparticles (Cu NPs) have widespread application because of their special physicochemical characteristics, however we need to more clearly study the toxicity mechanism of Cu NPs to ensure its safe use in pharmaceutical and animal feed. Thus, the aim of this study was to evaluate the effects and mechanisms of sub-chronic exposure to Cu NPs on renal CYP450 s of rats. In this study, we investigated the effects of Cu NPs on renal oxidative stress, cytokines and histopathology of rats. We found that Cu NPs (200 mg/kg) significantly disordered the function and structure of the kidney and caused a dose-dependent increase in oxidative stress and cytokines, which significantly decreased the levels of mRNA, protein, and activity of CYP450 s...
August 7, 2018: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/30090532/effects-of-ambient-pm-2-5-and-9-nitroanthracene-on-dna-damage-and-repair-oxidative-stress-and-metabolic-enzymes-in-the-lungs-of-rats
#20
Ruijin Li, Lifang Zhao, Li Zhang, Minghui Chen, Jing Shi, Chuan Dong, Zongwei Cai
Ambient fine particulate matter (PM2.5 ) is a complex mixture associated with lung cancer risk. PM2.5 -bound nitro-polycyclic aromatic hydrocarbons (NPAHs) have been demonstrated to possess mutagenicity and carcinogenicity. Previous studies showed that PM2.5 induced DNA damage, whereas there is little knowledge of whether 9-nitroanthracene (9-NA), a typical compound of NPAHs in PM2.5 , causes DNA damage. Also, the regulating mechanisms of PM2.5 and 9-NA in DNA damage and repair are not yet fully established...
September 1, 2017: Toxicology Research
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