Article
Pharmacology & Pharmacy
Nouf Alshammari, Devaraj Venkatapura Chandrashekar, Mamunur Rashid, Reza Mehvar
Summary: This study found that rat brain mitochondria contain substantial amounts of CYP3A, which may have an impact on the pharmacology or toxicology of centrally acting xenobiotic and endogenous substrates.
FUNDAMENTAL & CLINICAL PHARMACOLOGY
(2023)
Review
Pharmacology & Pharmacy
Laura Molenaar-Kuijsten, Dorieke E. M. Van Balen, Jos H. Beijnen, Neeltje Steeghs, Alwin D. R. Huitema
Summary: Many oral anticancer drugs are metabolized by CYP3A. Recommendations for dealing with DDIs of these drugs when only data from strong CYP3A inhibitors or inducers is available have been provided. If data from moderate or weak inhibitors/inducers is not available, a change in exposure of 50% compared with strong inhibitors/inducers can be assumed.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Toxicology
Viktoriia Burkina, Galia Zamaratskaia, Sidika Sakalli, Pham Thai Giang, Vladimir Zlabek, Martin Kroyer Rasmussen
Summary: Rainbow trout piscine cytochrome P450 (CYP) enzymes are important for the metabolism of xenobiotics. Different tissues show varied mRNA expression and activity levels of CYP1A and CYP3A-like enzymes, with the intestine having the main expression site for CYP3A27 and CYP3A45. Exposure to beta-naphthoflavone significantly increases CYP activity, while ketoconazole inhibits BFCOD activity by 50-98% in all tissues. Further research is needed to identify all responsible CYP isoforms and their modes of regulation.
TOXICOLOGY LETTERS
(2021)
Article
Engineering, Electrical & Electronic
David C. Ferrier, Janice Kiely, Richard Luxton
Summary: This study presents an enzyme-based electrochemical biosensor for detecting propofol concentrations in total intravenous anesthesia. The sensor demonstrates high sensitivity and good specificity, making it a promising tool for real-time monitoring during the maintenance phase of anesthesia.
IEEE SENSORS JOURNAL
(2021)
Article
Pharmacology & Pharmacy
Vladimir Mishin, Diane E. Heck, Yi-Hua Jan, Jason R. Richardson, Jeffrey D. Laskin
Summary: A characteristic of cytochrome P450 (CYP) enzymes is their ability to produce H2O2, which can lead to cellular oxidative stress and tissue damage. This study aimed to determine if specific form inhibitors could differentiate between the monooxygenase and NADPH oxidase activities of CYP enzymes. The findings suggest that form-specific inhibitors can effectively distinguish these two activities.
TOXICOLOGY AND APPLIED PHARMACOLOGY
(2022)
Article
Pharmacology & Pharmacy
Jiao Luo, Mengyue Xie, Yufei Hou, Wanli Ma, Yuan Jin, Jing Chen, Chuanhai Li, Kunming Zhao, Ningning Chen, Lin Xu, Yanan Ji, Qianqian Zhang, Yuxin Zheng, Dianke Yu
Summary: The study investigated the regulation of CYP expression by miRNA in alcoholic hepatitis. It revealed that miR-148a promotes CYP2B6 expression by increasing mRNA stability, and identified HNF4A as a liver-specific transcription factor of miR-148a. These findings enhance understanding of dysregulated drug metabolism in AH patients and highlight an unconventional mechanism for epigenetic regulation of CYP gene expression.
BIOCHEMICAL PHARMACOLOGY
(2021)
Article
Multidisciplinary Sciences
Katalin Mango, Adam Ferenc Kiss, Ferenc Fekete, Reka Erdos, Katalin Monostory
Summary: The CYP2B6 enzyme is a major catalyst for the metabolism of several important drugs, and its function varies greatly among individuals due to both genetic and non-genetic factors. A study found that hepatic CYP2B6 activity is strongly correlated with CYP2B6 mRNA expression, and that both genetic and non-genetic factors can contribute to a mismatch between CYP2B6 genotype and phenotype.
SCIENTIFIC REPORTS
(2022)
Article
Biochemistry & Molecular Biology
Amira Hussain, Declan P. Naughton, James Barker
Summary: This study examined the inhibitory potency of ibuprofen, remdesivir, and omeprazole on cytochrome P450 enzymes using rat liver microsomes in vitro. The results showed that ibuprofen acts as a non-competitive inhibitor, while remdesivir exhibits a mixed inhibition pattern, and omeprazole inhibits enzyme activity uncompetitively.
Article
Biochemistry & Molecular Biology
Lei Hou, Yingying Zhao, Shiyu Zhao, Xuexia Zhang, Xia Yao, Jianjun Yang, Ziteng Wang, Shuaibing Liu
Summary: This study systematically characterized the UGTs enzymes involved in the formation of M4 and the inhibitory effects of ciprofol and its metabolite M4 on P450s enzymes. In vitro-in vivo extrapolation and PBPK simulations were performed to predict potential drug-drug interactions caused by ciprofol.
CHEMICO-BIOLOGICAL INTERACTIONS
(2024)
Article
Environmental Sciences
Jia-Yue Wang, Jing-Xin Li, Jing Ning, Xiao-Kui Huo, Zhen-Long Yu, Yan Tian, Bao-Jing Zhang, Yan Wang, Deng Sa, Ya-Chen Li, Xia Lv, Xiao-Chi Ma
Summary: This study investigates the oxidative metabolism of Dimethomorph (DMM) mediated by the human cytochrome P450 enzyme (CYP) and its toxicological effects. The study reveals that DMM is mainly metabolized through a two-step oxidation process mediated by CYP3A, and can cause mechanism-based inactivation (MBI) of CYP3A. Additionally, other common fungicides can inhibit the metabolism of DMM, leading to increased exposure to DMM in vivo.
SCIENCE OF THE TOTAL ENVIRONMENT
(2022)
Article
Medicine, Research & Experimental
Line Skute Braten, Magnus Ingelman-Sundberg, Marin M. Jukic, Espen Molden, Marianne Kristiansen Kringen
Summary: The study highlights the significant role of CYP2C19 and CYP2B6 gene variants in sertraline response, indicating the potential for more accurate dosing decisions in clinical practice.
CTS-CLINICAL AND TRANSLATIONAL SCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Amira Hussain, Declan P. Naughton, James Barker
Summary: The combination therapy of aspirin and dexamethasone for COVID-19 has gained global attention. This study used HPLC to evaluate the in vitro inhibition of CYP3A2 enzyme activity by aspirin and validated an efficient HPLC method. The results showed that aspirin competitively inhibits CYP3A2 activity with minimal risk.
Article
Plant Sciences
Saneesh Kumar, Patrick J. Bouic, Bernd Rosenkranz
Summary: The study evaluated the effects of Withania somnifera root extracts on cytochromes P450, finding that they may cause clinically significant herb-drug interactions by affecting the metabolism pathway of drugs such as rifampicin.
JOURNAL OF ETHNOPHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Arianna Giorgetti, Sara Amurri, Giulia Fazio, Carla Bini, Laura Anniballi, Filippo Pirani, Guido Pelletti, Susi Pelotti
Summary: In toxicogenetics, an integrative approach to predict phenotype based on post-mortem genotyping of drug-metabolizing enzymes can explain the cause of death and manner of death. However, concomitant drug use may lead to phenoconversion, resulting in a mismatch between genotype and observed metabolic profile. This study evaluated the phenoconversion of CYP2D6, CYP2C9, CYP2C19, and CYP2B6 drug-metabolizing enzymes in autopsy cases. Results showed a high rate of phenoconversion for all enzymes, with increased frequency of poor and intermediate metabolizers after phenoconversion. No association was found between phenotypes and cause/manner of death, indicating the need for further research in the post-mortem setting.
Article
Chemistry, Medicinal
Longqiang Li, Zhou Lu, Guixia Liu, Yun Tang, Weihua Li
Summary: In this study, conventional machine learning and deep learning models were developed to predict CYP2B6 inhibitors and substrates. The best CYP2B6 inhibitor model achieved AUC values of 0.95 and 0.75 with 10-fold cross-validation and the test set, respectively. The best CYP2B6 substrate model produced AUC values of 0.93 and 0.90 with 10-fold cross-validation and the test set, respectively. The models were validated using external validation sets and several significant substructural fragments relevant to CYP2B6 inhibitors and substrates were identified.
CHEMICAL RESEARCH IN TOXICOLOGY
(2023)