Article
Biochemistry & Molecular Biology
Jiri Vrba, Barbora Papouskova, Katerina Lnenickova, Pavel Kosina, Vladimir Kren, Jitka Ulrichova
Summary: 2,3-Dehydrosilybin A and B are preferentially metabolized through conjugation reactions, with several human UGT and SULT enzymes potentially playing a role in these conjugations.
Article
Pharmacology & Pharmacy
Jingyun Li, Angela L. Chiew, Geoffrey K. Isbister, Stephen B. Duffull
Summary: Insufficient sulfation plays a critical role in shifting paracetamol metabolism towards toxic oxidation pathways, increasing the risk of liver toxicity. Serum inorganic sulfate is proposed as a biomarker for potential paracetamol-induced liver toxicity and a target for treatment.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Yunjiao Wu, Swantje Voller, Elke H. J. Krekels, Daniella W. E. Roofthooft, Sinno H. P. Simons, Dick Tibboel, Robert B. Flint, Catherijne A. J. Knibbe
Summary: This study aimed to quantify the maturation of paracetamol elimination pathways in preterm neonates born below 32 weeks of gestation. The results showed that birthweight and postnatal age were the most important factors affecting paracetamol clearance and its glucuronidation, sulfation, and oxidation. Therefore, dosing based on bodyweight alone will not lead to consistent paracetamol concentrations among preterm neonates.
PHARMACEUTICAL RESEARCH
(2023)
Article
Pharmacology & Pharmacy
Ana Loureiro, Carlos Fernandes-Lopes, Maria Joao Bonifacio, Filipa Sousa, Laszlo E. Kiss, Patricio Soares-da-Silva
Summary: Opicapone is a selective catechol-O-methyltransferase inhibitor that has been authorized for marketing in Europe, Japan, and the United States. This study investigated the metabolism and excretion of Opicapone in rats and found that it is rapidly absorbed, widely distributed in peripheral tissues, metabolized mainly through conjugation pathways, and primarily excreted in feces.
PHARMACOLOGY RESEARCH & PERSPECTIVES
(2022)
Article
Gastroenterology & Hepatology
Pengfei Xu, Yue Xi, Pengcheng Wang, Zigmund Luka, Meishu Xu, Hung-Chun Tung, Jingyuan Wang, Songrong Ren, Dechun Feng, Bin Gao, Aatur D. Singhi, Satdarshan P. Monga, John D. York, Xiaochao Ma, Zhiying Huang, Wen Xie
Summary: This study reveals the important role of PAPSS2 in APAP-induced acute liver failure. PAPSS2 protects liver cells from damage by increasing hepatic antioxidative capacity through the activation of the p53-p2-Nrf2 axis.
Article
Toxicology
Vlasia Kastrinou Lampou, Birk Poller, Felix Huth, Audrey Fischer, Gerd A. Kullak-Ublick, Michael Arand, Heiko S. Schadt, Gian Camenisch
Summary: Bile acid (BA) homeostasis is a complex process involving hydroxylation, glucuronidation, and sulfation reactions. This study investigated the key enzymes in BA metabolism and identified CYP3A4, UGT1A3, UGT2B7, and SULT2A1 as major contributors. The inhibition of these enzymes is considered critical in drug-induced cholestasis and should be considered in preclinical development.
TOXICOLOGY IN VITRO
(2023)
Article
Chemistry, Multidisciplinary
Lu-lu Pan, Yong Yang, Min Hui, Shuo Wang, Cui-yun Li, Hong Zhang, Yan-hua Ding, Li Fu, Xing-xing Diao, Da-fang Zhong
Summary: This study aimed to analyze the pharmacokinetics, metabolism and excretion routes of forsythin in humans, and determine the major enzymes and transporters involved in these processes. The research found that sulfation dominated the metabolism and pharmacokinetics of forsythin, with the sulfate conjugate being excreted mainly in the urine. Sulfotransferase 1A1 and UDP-glucuronosyltransferase 1A8 were identified as the most active hepatic enzymes involved in the formation of specific metabolites.
ACTA PHARMACOLOGICA SINICA
(2021)
Article
Chemistry, Medicinal
Seong-Wook Seo, Dong-Gyun Han, Young Mee Baek, Min Chul Park, Jin-Wook Yoo, Yunjin Jung, Han-Joo Maeng, Heejoon Myung, In-Soo Yoon
Summary: This study comprehensively investigated the oral absorption and intestinal/hepatic metabolism of alizarin. It found that alizarin has low stability in the intestine and low hepatic metabolism, resulting in a low oral bioavailability.
DRUG DEVELOPMENT RESEARCH
(2023)
Article
Medicine, Research & Experimental
Dong-Gyun Han, Seong-Wook Seo, Eugene Choi, Min-Soo Kim, Jin-Wook Yoo, Yunjin Jung, In-Soo Yoon
Summary: Resveratrol, a natural polyphenolic phytoalexin, is a dietary supplement that improves the outcomes of metabolic, cardiovascular, and other age-related diseases due to its diverse pharmacological activities. This study developed a physiologically-based pharmacokinetic (PBPK) model that accurately describes and predicts the systemic exposure profiles of resveratrol in clinical settings, and revealed the significant contributions of gut first-pass metabolism and enterohepatic circulation to the oral bioavailability of resveratrol.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Article
Gastroenterology & Hepatology
Xinran Cai, Sihan Li, Xuemei Zeng, Meishu Xu, Zehua Wang, Aatur D. Singhi, Daolin Tang, Song Li, Nathan A. Yates, Da Yang, Wen Xie
Summary: This study found that the SLC35B2-TPST2 axis of tyrosine sulfation plays a crucial role in the growth and metastasis of pancreatic ductal adenocarcinoma (PDAC). Inhibition of SLC35B2 or TPST2 expression, and pharmacological inhibition of sulfation, can inhibit PDAC cell proliferation and migration. TPST2 deficiency also inhibits tumor growth and metastasis. Mechanistically, integrin beta 4 was identified as a novel substrate of TPST2, and inhibition of sulfation destabilizes integrin beta 4 protein, which may account for the suppression of metastasis.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Hassan Salhab, Declan P. Naughton, James Barker
Summary: This study investigated the inhibitory effect of salicylic acid on UGT2B17 enzyme activity using an in vitro UGT2B17 assay. The assay showed good linearity, recovery, accuracy, reproducibility, and precision, with stable testosterone and testosterone glucuronide levels up to 72 hours. Salicylic acid was found to uncompetitively inhibit UGT2B17 enzyme activity, suggesting minimal potential for drug interactions in humans that are UGT2B17 enzyme substrates.
Article
Agriculture, Multidisciplinary
Kota Taniwa, Kazuma Murakami, Yoshiki Sakaguchi, Naotaka Izuo, Mizuho Hanaki, Nobuaki Sampa, Toshiaki Kume, Takahiko Shimizu, Kazuhiro Irie
Summary: This study detected the conjugated metabolites of green perilla-derived chalcone and taxifolin in the brain, small intestine, and plasma of mice, and found that these metabolites can inhibit the aggregation of Aβ42, which may be beneficial for the treatment of Alzheimer's disease.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2023)
Article
Environmental Sciences
Ana Filipa Nogueira, Bruno Nunes
Summary: The study examined the effects of paracetamol on the polychaete Hediste diversicolor, showing significant impacts on behavior, oxidative stress biomarkers, and anti-inflammatory activity biomarkers. Exposure to paracetamol altered behavior, increased oxidative stress biomarker activities, and inhibited the anti-inflammatory activity biomarker, indicating potential deleterious effects on marine ecosystems and marine invertebrates.
ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH
(2021)
Article
Toxicology
Hisayoshi Omori, Junko Chikamoto, Megumi Nagahara, Maki Hirata, Takeshige Otoi
Summary: This study investigated the variations in bilirubin metabolic function of canine and human hepatocyte spheroids formed in a 3D culture system. The results showed that the inhibitors atazanavir and ritonavir significantly inhibited the formation of bilirubin glucuronides, especially in human hepatocyte spheroids.
TOXICOLOGY IN VITRO
(2023)
Article
Chemistry, Physical
Yanfang Chen, Xiaojie Sui, Tiantong Zhang, Jing Yang, Lei Zhang, You Han
Summary: Understanding the mechanism of ice recrystallization inhibition (IRI) is crucial for designing new antifreeze protein mimetics and reducing IR-related damage. Through quantitative experimental methods and molecular dynamics simulations, we demonstrate that zwitterionic poly(carboxybetaine methacrylate) (PCBMA) can effectively inhibit ice recrystallization. This study uncovers the atomic-level details of the IRI mechanism in zwitterionic antifreeze protein mimetics and offers insights for the development of next-generation antifreeze protein mimetics.
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2023)
Article
Biochemistry & Molecular Biology
Michael W. H. Coughtrie
CHEMICO-BIOLOGICAL INTERACTIONS
(2016)
Article
Substance Abuse
Luis R. Vaz, Paul Aveyard, Sue Cooper, Jo Leonardi-Bee, Tim Coleman
NICOTINE & TOBACCO RESEARCH
(2016)
Article
Biochemistry & Molecular Biology
X. Mao, C. Gauche, M. W. H. Coughtrie, C. Bui, S. Gulberti, F. Merhi-Soussi, N. Ramalanjaona, I. Bertin-Jung, A. Diot, D. Dumas, N. De Freitas Caires, A. M. Thompson, J-C Bourdon, M. Ouzzine, S. Fournel-Gigleux
Article
Pharmacology & Pharmacy
Gurinder Walia, Alexander D. Smith, Zoe Riches, Abby C. Collier, Michael W. H. Coughtrie
Meeting Abstract
Pharmacology & Pharmacy
Zoe Riches, Gurinder Walia, Jacob Berman, Michael Coughtrie, Abby Collier
JOURNAL OF PHARMACOLOGICAL AND TOXICOLOGICAL METHODS
(2017)
Review
Pharmacology & Pharmacy
Yuejian Liu, MichaelW. H. Coughtrie
Article
Biochemistry & Molecular Biology
Katalin Revesz, Blanka Toth, Adam G. Staines, Michael W. H. Coughtrie, Jozsef Mandl, Miklos Csala
Editorial Material
Medicine, General & Internal
Nina Di Pietro, Judy Illes
CANADIAN MEDICAL ASSOCIATION JOURNAL
(2014)
Article
Health Care Sciences & Services
Sue Cooper, Sarah Lewis, James G. Thornton, Neil Marlow, Kim Watts, John Britton, Matthew J. Grainge, Jaspal Taggar, Holly Essex, Steve Parrott, Anne Dickinson, Rachel Whitemore, Tim Coleman
HEALTH TECHNOLOGY ASSESSMENT
(2014)
Article
Medicine, General & Internal
Tim Coleman, Sue Cooper, James G. Thornton, Matthew J. Grainge, Kim Watts, John Britton, Sarah Lewis
NEW ENGLAND JOURNAL OF MEDICINE
(2012)
Article
Pharmacology & Pharmacy
Kanika V. Choughule, Charles W. Locuson, Michael W. H. Coughtrie
Article
Critical Care Medicine
Sue Cooper, Jaspal Taggar, Sarah Lewis, Neil Marlow, Anne Dickinson, Rachel Whitemore, Tim Coleman
LANCET RESPIRATORY MEDICINE
(2014)
Article
Chemistry, Multidisciplinary
Alexander D. Smith, Brent D. G. Page, Abby C. Collier, Michael W. H. Coughtrie
Article
Pharmacology & Pharmacy
Michael J. J. Doerksen, Denny Seo, Alexander D. D. Smith, Robert S. S. Jones, Michael W. H. Coughtrie, Abby C. C. Collier
Summary: In this study, hepatic GST conjugation was investigated in mouse and rat strains compared to humans. The results showed that all mouse strains had higher activities of total cytosolic GST, GST-M, GST-T, and microsomal GST compared to humans, with some strains also having higher GST-P activities. Sex differences were observed in all strains for several GST activities. Similarly, rats exhibited higher activities of GST-M and GST-T compared to humans, with some strains also showing higher activities of GST-P, total cytosolic GST, and microsomal GST. Sex differences were also observed in some strains for certain GST activities. These findings highlight the importance of careful selection of animal models in pre-clinical studies where GSTs are involved in drug metabolism.
Article
Pharmacology & Pharmacy
Sjoerd de Hoogd, Pyry A. J. Valitalo, Albert Dahan, Simone van Kralingen, Michael M. W. Coughtrie, Eric P. A. van Dongen, Bert van Ramshorst, Catherijne A. J. Knibbe
CLINICAL PHARMACOKINETICS
(2017)