Article
Pharmacology & Pharmacy
Marlies Oorts, Pieter Van Brantegem, Neel Deferm, Sagnik Chatterjee, Erwin Dreesen, Axelle Cooreman, Mathieu Vinken, Lysiane Richert, Pieter Annaert
Summary: Bosentan was evaluated at therapeutically relevant concentrations (2.5-25 μM) in sandwich-cultured human hepatocytes. It altered bile salt disposition and inhibited canalicular secretion of glycochenodeoxycholic acid (GCDCA). Within 24 hours, bosentan caused a shift from canalicular to sinusoidal efflux of GCDCA. These results also indicated reduced GCDCA formation. This study confirmed a direct effect of bosentan on chenodeoxycholic acid conjugation with glycine in liver S9 fraction.
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
(2021)
Article
Biochemistry & Molecular Biology
Yung-Te Hou, Chia-Chun Wu, Wen-Ting Wang, Wen-Tse Yang, Ying-Hsiu Liao, Chien-Yu Chen
Summary: In this study, RNA-Seq was used to monitor the maturity and dynamic characteristics of in vitro hepatocyte cultures. The results showed that RNA-Seq can be used to infer the success of in vitro hepatocyte cultures and provide a more comprehensive list of factors related to hepatocyte differentiation. This monitoring system has high potential in medical applications and may also be a novel method for diagnosing liver-related diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Pharmacology & Pharmacy
Taleah Farasyn, Chao Xu, Wei Yue
Summary: The study aimed to develop a novel rat SCH model expressing human OATP1B3 to study the hepatic disposition of OATP1B3 substrates. The results showed that expressing human OATP1B3 in rat SCH significantly increased the cellular accumulation of OATP1B3 substrates without affecting biliary excretion.
JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES
(2021)
Article
Toxicology
Takashi Kitaguchi, Shinichiro Horiuchi, Yukie Kuroda, Katsutoshi Ohno, Kazuhiro Kobayashi, Mitsuru Tanaka, Seiichi Ishidaz
Summary: A simple in vitro culture method using cryopreserved human hepatocytes was developed to generate extended and functional bile canaliculi, and to evaluate the uptake and biliary excretion of compounds. Positive biliary excretion index (BEI) was observed for reported biliary-excreted compounds, while no difference in BEI was seen for a nonbiliary-excreted compound. Additionally, specific food-related compounds with reported biliary transporter involvement exhibited positive BEIs. This in vitro system can be used to predict the biliary excretion of pharmaceutical and food-related compounds.
JOURNAL OF TOXICOLOGICAL SCIENCES
(2023)
Article
Toxicology
Annelies Noorlander, Eric Fabian, Bennard van Ravenzwaay, Ivonne M. C. M. Rietjens
Summary: The study aimed to develop a generic rat PBK model with active biliary excretion using E(2)17βG. The scaling factor for the conversion of in vitro to in vivo parameters was defined based on fit to experimental data, resulting in successful prediction of E(2)17βG levels. This study demonstrates the feasibility of incorporating biliary excretion in a PBK model using primary hepatocytes.
ARCHIVES OF TOXICOLOGY
(2021)
Article
Pharmacology & Pharmacy
Congrong Niu, Bill Smith, Yurong Lai
Summary: This study characterized the gene induction by ligands of CAR and AhR in human hepatocytes, showing distinct effects on metabolizing enzyme and drug transporter genes. Different inducers had varying degrees of effects on specific genes, highlighting the importance of assessing transporter gene inductions alongside metabolizing enzyme genes.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Pharmacology & Pharmacy
Taleah Farasyn, Sonia Pahwa, Chao Xu, Wei Yue
Summary: This study demonstrates that pre-incubation with OATP1B inhibitors potentiates inhibitory effects in physiologically relevant primary human hepatocytes, supporting the rationale of the current US FDA draft guidance. IC50 values after inhibitor-preincubation in transporter-expressing cell lines may be used for DDI prediction for the purpose of mitigating false-negative OATP-mediated DDI prediction.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2021)
Article
Chemistry, Multidisciplinary
Ya-li Wu, Ya-ru Xue, Zi-tao Guo, Zhen-dong Chen, Xin-yu Ge, Da-fang Zhong, Xing-xing Diao
Summary: Furmonertinib has been identified as a potent CYP3A4 inducer, comparable to rifampin, making it a potential positive control for evaluating the induction potential of other drug candidates in preclinical studies. Results from the study show that furmonertinib induced CYP3A4 enzyme activity in a manner similar to rifampin in in vitro experiments.
ACTA PHARMACOLOGICA SINICA
(2022)
Article
Chemistry, Inorganic & Nuclear
Oscar A. Lenis-Rojas, Rui Cabral, Beatriz Carvalho, Sofia Friaes, Catarina Roma-Rodrigues, Jhonathan A. A. Fernandez, Sabela F. Vila, Laura Sanchez, Clara S. B. Gomes, Alexandra R. Fernandes, Beatriz Royo
Summary: A new series of half-sandwich ruthenium(II) compounds bearing 1,2,3-triazole ligands were synthesized and fully characterized. Compounds 1 and 3 showed good cytotoxic activity against ovarian cancer cells with low toxicity both in vitro and in vivo.
INORGANIC CHEMISTRY
(2021)
Article
Cell Biology
Klaudia Sztolsztener, Karolina Konstantynowicz-Nowicka, Anna Pedzinska-Betiuk, Adrian Chabowski
Summary: This study investigated the effects of cannabigerol (CBG) on the composition of extracellular matrix (ECM) in fibrotic liver cells. The results showed that low concentrations of CBG reduced the expression of TGF-beta 1 and inhibited the deposition of collagen, suggesting that CBG may promote fibrosis regression and regeneration.
Article
Integrative & Complementary Medicine
Lachin Mousavi, Elham Zadeh-Hashem, Mehdi Imani
Summary: The current study evaluated the protective effects of luteolin against beta-cyfluthrin-induced toxicity on rat hepatocytes. The results showed that luteolin could significantly reduce the damage caused by beta-cyfluthrin to the liver cells, possibly by attenuating oxidative/nitrosative reactions and increasing antioxidant capacity.
EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Terufumi Yoshida, Tadayoshi Okumura, Yoshiyuki Matsuo, Tetsuya Okuyama, Taku Michiura, Masaki Kaibori, Nodoka Umezaki, Hidemasa Bono, Kiichi Hirota, Mitsugu Sekimoto
Summary: This study investigated the effect of Roxadustat and hypoxia-induced HIF activation on NO production in hepatocytes. It was found that HIF activation inhibited IL-1β-induced iNOS expression and subsequent NO production by suppressing the NF-κB signaling pathway. Additionally, Roxadustat treatment suppressed the expression of pro-inflammatory genes and may have hepatoprotective effects.
NITRIC OXIDE-BIOLOGY AND CHEMISTRY
(2022)
Article
Engineering, Biomedical
Zhengpei Zhang, Farasat Zaman, Tobia Sebastiano Nava, Tim R. J. Aeppli, Elena M. Gutierrez-Farewik, Artem Kulachenko, Lars Savendahl
Summary: To study the potential clinical applications of mechanical loading in modulating bone growth, a portable loading device was developed. The device allows high-precision force control and can have different effects on bone growth. This device enables further preclinical studies exploring the potential clinical applications of mechanical loading.
ANNALS OF BIOMEDICAL ENGINEERING
(2023)
Article
Pharmacology & Pharmacy
AtLee T. D. Watson, Benjamin C. Moeller, Melanie Doyle-Eisele, Edwin Garner, Chad R. Blystone, Jacob D. McDonald, Suramya Waidyanatha
Summary: The study investigated the disposition and metabolism of ethylene glycol 2-ethylhexyl ether (EGEHE) in rats and mice, showing rapid clearance and excretion in both species. EGEHE was well absorbed and distributed in tissues, with liver and kidney containing the highest levels. Metabolism of EGEHE was extensive, with little to no parent compound detected in urine. The study also found no significant dose, species, or sex differences in the disposition and metabolism of EGEHE.
Article
Toxicology
Annelies Noorlander, Sebastiaan Wesseling, Ivonne M. C. M. Rietjens, Bennard van Ravenzwaay
Summary: This study successfully incorporated active renal excretion via OCT2 transporter into a generic rat PBK model to predict the kinetics of MQ in rats using SA7K cells and MQ as the model compound. By applying a scaling factor to correct for differences in OCT2 activity and species variations, the model predictions improved significantly.
TOXICOLOGY LETTERS
(2021)