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https://www.readbyqxmd.com/read/28934153/inhibitory-effect-of-selaginellins-from-selaginella-tamariscina-beauv-spring-against-cytochrome-p450-and-uridine-5-diphosphoglucuronosyltransferase-isoforms-on-human-liver-microsomes
#1
Jae-Kyung Heo, Phi-Hung Nguyen, Won Cheol Kim, Nguyen Minh Phuc, Kwang-Hyeon Liu
Selaginella tamariscina (Beauv.) has been used for traditional herbal medicine for treatment of cancer, hepatitis, and diabetes in the Orient. Numerous bioactive compounds including alkaloids, flavonoids, lignans, and selaginellins have been identified in this medicinal plant. Among them, selaginellins having a quinone methide unit and an alkylphenol moiety have been known to possess anticancer, antidiabetic, and neuroprotective activity. Although there have been studies on the biological activities of selaginellins, their modulatory potential of cytochrome P450 (P450) and uridine 5'-diphosphoglucuronosyltransferase (UGT) activities have not been previously evaluated...
September 21, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28924552/schisandra-sphenanthera-extract-wuzhi-tablet-protects-against-chronic-binge-and-acute-alcohol-induced-liver-injury-by-regulating-the-nrf2-are-pathway-in-mice
#2
Xuezhen Zeng, Xi Li, Chenshu Xu, Fulin Jiang, Yufei Mo, Xiaomei Fan, Yaoting Li, Yiming Jiang, Dongshun Li, Min Huang, Huichang Bi
Alcohol abuse leads to alcoholic liver disease and no effective therapy is currently available. Wuzhi Tablet (WZ), a preparation of extract from Schisandra sphenanthera that is a traditional hepato-protective herb, exerted a significant protective effect against acetaminophen-induced liver injury in our recent studies, but whether WZ can alleviate alcohol-induced toxicity remains unclear. This study aimed to investigate the contribution of WZ to alcohol-induced liver injury by using chronic-binge and acute models of alcohol feeding...
September 2017: Acta Pharmaceutica Sinica. B
https://www.readbyqxmd.com/read/28918601/effects-of-phoxim-induced-hepatotoxicity-on-sd-rats-and-the-protection-of-vitamin-e
#3
Jing Zhang, Wentao Song, Yuecheng Sun, Anshan Shan
Currently, public pay more attention to the adverse effect of organophosphate pesticides on human and animal health and on the environment in developing nations. Vitamin E may protect the hepatocyte and increase the function of liver. The study was to investigate the effects of phoxim-induced hepatotoxicity on Sprague Dawley (SD) rats and the protection of vitamin E. SD rats received by gavage 180 mg kg(-1) (per body weight) of phoxim, 200 mg kg(-1) (per body weight) of vitamin E, and phoxim + vitamin E...
September 16, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/28904078/towards-a-systems-approach-to-human-cytochrome-p450-ensemble-interactions-between-cyp2d6-and-cyp2e1-and-their-functional-consequences
#4
Dmitri R Davydov, Nadezhda Y Davydova, John T Rodgers, Thomas H Rushmore, Jeffrey P Jones
Functional cross-talk among human drug-metabolizing cytochromes P450 through their association is a topic of emerging importance. Here we studied the interactions of human CYP2D6, a major metabolizer of psychoactive drugs, with one of the most prevalent human P450 enzymes, ethanol-inducible CYP2E1. Detection of P450-P450 interactions was accomplished through luminescence resonance energy transfer (LRET) between labeled proteins incorporated into human liver microsomes and the microsomes of insect cells containing NADPH-cytochrome P450 reductase...
September 13, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28900877/genetic-polymorphisms-of-slco1b1-cyp2e1-and-ugt1a1-and-susceptibility-to-anti-tuberculosis-drug-induced-hepatotoxicity-a-chinese-population-based-prospective-case-control-study
#5
Qin Sun, Hai-Peng Liu, Rui-Juan Zheng, Peng Wang, Zhi-Bin Liu, Wei Sha, He-Ping Xiao
BACKGROUND: Drug transporters and drug-metabolizing enzymes have been linked to drug-induced hepatotoxicity. Solute carrier organic anion transporter family member 1B1 (SLCO1B1), cytochrome P450 2E1 (CYP2E1), and UDP glucuronosyltransferase 1A1 (UGT1A1) were selected as candidate genes to explore their association with susceptibility to anti-tuberculosis drug-induced hepatotoxicity (ATDH). METHODS: Thirty-four tag single nucleotide polymorphisms (tagSNPs) in SLCO1B1, CYP2E1, and UGT1A1 with 10-kb expansion up- and down-stream were genotyped in 461 patients with ATDH and 466 patients without ATDH in a prospective 1:1 matched case-control study...
September 12, 2017: Clinical Drug Investigation
https://www.readbyqxmd.com/read/28895652/quantitative-proteomics-and-targeted-fatty-acids-analysis-reveal-the-damage-of-triptolide-in-liver-and-kidney
#6
Menglin Li, Ting Hu, Cai Tie, Liang Qu, Hao Zheng, Jinlan Zhang
Triptolide (TP), the major active component in Tripterygium wilfordii Hook. f., is widely used for the treatment of rheumatoid arthritis and autoimmune disease. However, organ toxicity, especially hepatotoxicity and nephrotoxicity, limits its clinical application. To fully understand the mechanism underlying TP toxicity, iTRAQ-based 2D-LC-MS/MS proteomics was used to detect differentially expressed proteins in the livers and kidneys of mice administered the LD50 dose of TP. Functional annotation revealed that multiple pathways are involved in TP toxicity, including acute-phase response signaling, the antigen presentation pathway, FXR/RXR activation, LPS/IL-1-mediated inhibition of RXR function and EIF2 signaling...
September 12, 2017: Proteomics
https://www.readbyqxmd.com/read/28890346/hepatoprotective-effects-of-methyl-ferulic-acid-on-alcohol-induced-liver-oxidative-injury-in-mice-by-inhibiting-the-nox4-ros-mapk-pathway
#7
Chen Li, Li Li, Cheng-Fang Yang, Yu-Juan Zhong, Dan Wu, Lin Shi, Li Chen, Yong-Wen Li
AIMS: The present study aimed to investigate the hepatoprotective effects of Methyl ferulic acid (MFA) against oxidative stress and apoptosis as well as inflammation in mice with liver injury induced by alcohol and its underlying mechanisms. METHODS: C57BL/6 mice were divided into a control group,a model group, and Methyl ferulic acid with high dosage (20 mg/kg), moderate dosage (10 mg/kg) and low dosage (5 mg/kg) groups. The general condition and organ index of each group were investigated...
September 7, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28882082/changes-in-hepatic-phase-i-and-phase-ii-biotransformation-enzyme-expression-and-glutathione-levels-following-atrazine-exposure-in-female-rats
#8
Arthur D Zimmerman, Charles B Breckenridge, Kun D Yi, Pragati Sawhney Coder, Desiree Wanders, Robert L Judd, Chad D Foradori
1. To determine the effects of repeated atrazine (ATR) treatment on hepatic phase I and II enzymes, adult female rats were treated with vehicle or 100mg/kg of ATR for 1, 2, 3 or 4 days. Glutathione-s-transferases (GST) mRNA expression, protein levels (mu, pi, alpha, omega), and activity (cytosolic and microsomal), along with bioavailable glutathione (GSH) were assayed. 2. GST expression, concentrations, and activity were increased, along with GSH levels, in animals treated with ATR for 3 and 4 days. 3. A subsequent study was performed with animals treated with vehicle, 6...
September 8, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/28872689/metabolic-interactions-between-acetaminophen-paracetamol-and-two-flavonoids-luteolin-and-quercetin-through-in-vitro-inhibition-studies
#9
Lei Cao, Awewura Kwara, David J Greenblatt
OBJECTIVES: Excessive exposure to acetaminophen (APAP, paracetamol) can cause liver injury through formation of a reactive metabolite that depletes hepatic glutathione and causes hepatocellular oxidative stress and damage. Generation of this metabolite is mediated by Cytochrome-P450 (CYP) isoforms, mainly CYP2E1. A number of naturally occurring flavonoids can mitigate APAP-induced hepatotoxicity in experimental animal models. Our objective was to determine the mechanism of these protective effects and to evaluate possible human applicability...
September 5, 2017: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/28867436/effects-of-diosmetin-on-nine-cytochrome-p450-isoforms-ugts-and-three-drug-transporters-in-vitro
#10
Jun-Jun Chen, Jing-Xian Zhang, Xiang-Qi Zhang, Mei-Juan Qi, Mei-Zhi Shi, Jiao Yang, Ke-Zhi Zhang, Cheng Guo, Yong-Long Han
Diosmetin (3', 5, 7-trihydroxy-4'-methoxyflavone), a natural flavonoid from traditional Chinese herbs, has been used in various medicinal products because of its anticancer, antimicrobial, antioxidant, estrogenic and anti-inflammatory activity. However, flavonoids could affect the metabolic enzymes and cause drug-drug interactions (DDI), reducing the efficacy of co-administered drugs and potentially resulting in serious adverse reactions. To evaluate its potential to interact with co-administered drugs, the IC50 value of phase I cytochrome P450 enzymes (CYPs), phase II UDP-glucuronyltransferases (UGTs) and hepatic uptake transporters (organic cation transporters (OCTs), organic anion transporter polypeptides (OATPs) and Na(+)-taurocholate cotransporting polypeptides (NTCPs)) were examined in vitro by LC-MS/MS...
September 1, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28864499/ethanol-metabolism-by-alcohol-dehydrogenase-or-cytochrome-p450-2e1-differentially-impairs-hepatic-protein-trafficking-and-growth-hormone-signaling
#11
Erin E Doody, Jennifer L Groebner, Jetta R Walker, Brittnee M Frizol, Dean J Tuma, David J Fernandez, Pamela L Tuma
The liver metabolizes alcohol using alcohol dehydrogenase (ADH) and cytochrome P450 2E1 (CYP2E1). Both enzymes metabolize ethanol into acetaldehyde, but CYP2E1 activity also results in the production of reactive oxygen species (ROS) that promote oxidative stress. We have previously shown that microtubules are hyperacetylated in ethanol-treated polarized, hepatic WIF-B cells and livers from ethanol fed rats. We have also shown that enhanced protein acetylation correlates with impaired clathrin-mediated endocytosis, constitutive secretion and nuclear translocation and that the defects are likely mediated by acetaldehyde...
September 1, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28843596/cytochrome-p450-2e1-is-involved-in-aging-related-kidney-damage-in-mice-through-increased-nitroxidative-stress
#12
Mohamed A Abdelmegeed, Youngshim Choi, Seung-Kwoon Ha, Byoung-Joon Song
The aim of this study was to investigate the role of cytochrome P450-2E1 (CYP2E1) in aging-dependent kidney damage since it is poorly understood. Young (7 weeks) and aged female (16-17 months old) wild-type (WT) and Cyp2e1-null mice were used. Kidney histology showed that aged WT mice exhibited typical signs of kidney aging such as cell vacuolation, inflammatory cell infiltration, cellular apoptosis, glomerulonephropathy, and fibrosis, along with significantly elevated levels of renal TNF-α and serum creatinine than all other groups...
August 24, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28838263/evaluation-of-oxidative-stress-via-protein-expression-of-glutathion-s-transferase-and-cytochrome-p450-cyp450-isoenzymes-in-psoriasis-vulgaris-patients-treated-with-methotrexate
#13
Ozge Akbulak, Ayse Serap Karadag, Necmettin Akdeniz, Seyma Ozkanli, Emin Ozlu, Ebru Zemheri, Serpil Oguztuzun
INTRODUCTION: Oxidative stress is the imbalance between oxidant-antioxidant systems and may play a major role in the psoriasis pathogenesis. Cytochrome (CYP) is a family of enzymes which are responsible for the metabolism of various endogenous and exogenous substances such as drug metabolism. Most importantly, the antioxidant system is the Glutathione- S transferases (GST) which decrease oxidative stress by reducing oxidative products. AIM: We aimed to evaluate the expressions of isoenzymes of GST and CYP families and the beneficial role of metotrexate (MTX) in this process...
August 24, 2017: Cutaneous and Ocular Toxicology
https://www.readbyqxmd.com/read/28835442/cyp-mediated-sulfoximine-de-imination-of-azd6738
#14
Barry C Jones, Roshini Markandu, Chungang Gu, Graeme Scarfe
In hepatic S9 and human liver microsomes (HLM) the sulfoximine moiety of the ATR inhibitor AZD6738 is metabolised to its corresponding sulfoxide (AZ8982) and sulfone (AZ0002). The initial de-imination to AZ8982 is nominally a reductive reaction but in HLM required NADPH and was inhibited by 1-aminobenzotriazole (ABT) at 1mM. Studies in a panel of 11 recombinant cytochrome P450s (CYPs) - CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1 CYP2J2, CYP3A4 and CYP3A5 - confirmed that the de-imination was an oxidative process, mediated largely by CYP2C8 with some CYP2J2 involvement, whilst the subsequent oxidation to the sulfone was carried out largely by CYP2J2, CYP3A4 and CYP3A5...
August 23, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28832650/fructose-diet-alleviates-acetaminophen-induced-hepatotoxicity-in-mice
#15
Sungjoon Cho, Ashutosh Tripathi, George Chlipala, Stefan Green, Hyunwoo Lee, Eugene B Chang, Hyunyoung Jeong
Acetaminophen (APAP) is a commonly used analgesic and antipyretic that can cause hepatotoxicity due to production of toxic metabolites via cytochrome P450 (Cyp) 1a2 and Cyp2e1. Previous studies have shown conflicting effects of fructose (the major component in Western diet) on the susceptibility to APAP-induced hepatotoxicity. To evaluate the role of fructose-supplemented diet in modulating the extent of APAP-induced liver injury, male C57BL/6J mice were given 30% (w/v) fructose in water (or regular water) for 8 weeks, followed by oral administration of APAP...
2017: PloS One
https://www.readbyqxmd.com/read/28827732/genetic-predisposition-to-lung-cancer-comprehensive-literature-integration-meta-analysis-and-multiple-evidence-assessment-of-candidate-gene-association-studies
#16
Junjun Wang, Qingyun Liu, Shuai Yuan, Weijia Xie, Yuan Liu, Ying Xiang, Na Wu, Long Wu, Xiangyu Ma, Tongjian Cai, Yao Zhang, Zhifu Sun, Yafei Li
More than 1000 candidate-gene association studies on genetic susceptibility to lung cancer have been published over the last two decades but with few consensuses for the likely culprits. We conducted a comprehensive review, meta-analysis and evidence strength evaluation of published candidate-gene association studies in lung cancer up to November 1, 2015. The epidemiological credibility of cumulative evidence was assessed using the Venice criteria. A total of 1018 publications with 2910 genetic variants in 754 different genes or chromosomal loci were eligible for inclusion...
August 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28807506/altered-vulnerability-to-asthma-at-various-levels-of-ambient-benzo-a-pyrene-by-ctla4-stat4-and-cyp2e1-polymorphisms
#17
Hyunok Choi, Nana Tabashidze, Pavel Rossner, Miroslav Dostal, Anna Pastorkova, Sek Won Kong, Hans Gmuender, Radim J Sram
BACKGROUND: Within fossil- and solid-fuel dependent geographic locations, mechanisms of air pollution-induced asthma remains unknown. In particular, sources of greater genetic susceptibility to airborne carcinogen, namely, benzo[a]pyrene (B[a]P) has never been investigated beyond that of a few well known genes. OBJECTIVES: To deepen our understanding on how the genotypic variations within the candidate genes contribute to the variability in the children's susceptibility to ambient B[a]P on doctor-diagnosed asthma...
August 11, 2017: Environmental Pollution
https://www.readbyqxmd.com/read/28805741/alcohol-and-cancer-mechanisms-and-therapies
#18
REVIEW
Anuradha Ratna, Pranoti Mandrekar
Several scientific and clinical studies have shown an association between chronic alcohol consumption and the occurrence of cancer in humans. The mechanism for alcohol-induced carcinogenesis has not been fully understood, although plausible events include genotoxic effects of acetaldehyde, cytochrome P450 2E1 (CYP2E1)-mediated generation of reactive oxygen species, aberrant metabolism of folate and retinoids, increased estrogen, and genetic polymorphisms. Here, we summarize the impact of alcohol drinking on the risk of cancer development and potential underlying molecular mechanisms...
August 14, 2017: Biomolecules
https://www.readbyqxmd.com/read/28803882/changes-in-coumarin-kinetics-and-subcellular-localization-of-cyp2e1-contribute-to-bile-duct-damage-and-reduce-hepatocellular-damage-after-repeated-administration-of-coumarin-in-rats
#19
Yasuhiro Tanaka, Wataru Fujii, Hisako Hori, Yoshinori Kitagawa, Kiyokazu Ozaki
Coumarin exhibits different hepatotoxicity in rats depending on the administration frequency. To investigate the underlying mechanisms for the differences, we administered coumarin to rats as a single dose or repeatedly for 4 weeks. We found large increases in blood levels of liver enzymes and noticeable centrilobular hepatic necrosis after a single dose of coumarin. After repeated administration, enzyme levels mildly increased, while those of γ-GTP and total bilirubin significantly increased, suggesting bile duct damage...
August 10, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28803762/apigenin-protects-against-alcohol-induced-liver-injury-in-mice-by-regulating-hepatic-cyp2e1-mediated-oxidative-stress-and-ppar%C3%AE-mediated-lipogenic-gene-expression
#20
Feng Wang, Jin-Cheng Liu, Rui-Jun Zhou, Xi Zhao, Mei Liu, Hua Ye, Mei-Lin Xie
Alcohol is a major cause of liver injury, and there are currently no ideal pharmacological reagents that can prevent or reverse this disease. Apigenin is one of the most common flavonoids present in numerous plants and has many beneficial effects. But whether or not apigenin may protect against alcohol-induced liver injury remains unknown. Our aim was to examine the effect and potential mechanisms. The experimental mice were given 56% erguotou wine or simultaneously given apigenin 150-300 mg/kg by gavage for 30 days...
August 10, 2017: Chemico-biological Interactions
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