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
Food Science & Technology
Takumi Sato, Ryota Shizu, Yoshie Miura, Takuomi Hosaka, Yuichiro Kanno, Takamitsu Sasaki, Kouichi Yoshinari
Summary: This study identified possible direct and indirect activators of rCAR by measuring Cyp2b1 mRNA levels and performing reporter assays. It demonstrated the usefulness of these methods in evaluating rCAR activation by chemicals.
FOOD AND CHEMICAL TOXICOLOGY
(2022)
Article
Gastroenterology & Hepatology
Jianliang Xu, P. Jaya Kausalya, Noemi Van Hul, Matias J. Caldez, Shiyi Xu, Alicia Ghia Min Ong, Wan Lu Woo, Safiah Mohamed Ali, Philipp Kaldis, Walter Hunziker
Summary: The study highlights the crucial role of Tjp2 in maintaining liver tissue barriers and bile transport processes. Deficiency in Tjp2 can lead to the formation of a model for cholestatic liver disease, and certain drugs such as ursodeoxycholic acid and 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene can partially alleviate this damage.
Article
Pharmacology & Pharmacy
Maike Gaehrs, Dieter Schrenk
Summary: NDL-PCBs can suppress UV-induced apoptosis in rat hepatocytes by activating CAR and PXR, and the effects on apoptosis by CAR or PXR activators are specific to CAR or PXR.
Review
Biochemistry & Molecular Biology
Sarah Da Won Bae, Romario Nguyen, Liang Qiao, Jacob George
Summary: CAR is a receptor that is predominantly expressed in the liver and interacts with key signaling pathways related to drug, energy, and bilirubin metabolism. While studies in animal models suggest a potential role of CAR in tumorigenesis, recent research has shown species differences and a possible tumor-suppressive role of CAR in liver cancer in humans. This review highlights the need for further exploration of CAR's role in human diseases, particularly cancers, with a focus on its emerging functions in liver cancer.
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER
(2021)
Review
Toxicology
Tomoya Yamada, Samuel M. Cohen, Brian G. Lake
Summary: Studies have shown that CAR activators in mice and rats can lead to liver tumors, but they do not stimulate increased hepatocellular proliferation in humans. Analysis of available data indicates that the established MOA for rodent liver tumor formation by CAR activators is not plausible for humans.
CRITICAL REVIEWS IN TOXICOLOGY
(2021)
Article
Multidisciplinary Sciences
Melissa M. Heintz, Jazmine A. Eccles, Emily M. Olack, Kristal M. Maner-Smith, Eric A. Ortlund, William S. Baldwin
Summary: In addition to over consumption, multiple factors contribute to obesity and non-alcoholic fatty liver disease (NAFLD). CYP2B6, a human detoxification enzyme, has been found to be associated with obesity. It metabolizes PUFAs, with a preference for ALA metabolism and PUFAs at the 9- and 13-positions. Research using transgenic mice showed that CYP2B6 has an anti-obesity effect, but to a lesser extent compared to Cyp2b in mice. The inhibition of CYP2B6 by xenobiotics or dietary fats can worsen obesity and metabolic disease by disrupting PUFA metabolism and producing key lipid metabolites.
Review
Pathology
Tomoya Yamada
Summary: Research has shown that PB can induce hepatocyte proliferation and tumor formation in mouse models, but in models with human hepatocytes, PB fails to increase human hepatocyte proliferation. This highlights the differences between human and rodent in terms of CAR-mediated liver tumor formation.
JOURNAL OF TOXICOLOGIC PATHOLOGY
(2021)
Review
Pharmacology & Pharmacy
Lesley A. Stanley, C. Roland Wolf
Summary: The use of in vitro models for hepatic metabolism and toxicity assessment is essential for evaluating drug candidates. HepG2 and HepaRG cell lines are commonly used, but HepG2 cells have limitations and lack drug-metabolizing capacity. HepaRG cells are more hepatocyte-like but have variability in data possibly due to complex differentiation protocols. Standardized protocols and validation of P450 regulation mechanisms are needed to utilize HepaRG cells effectively.
DRUG METABOLISM REVIEWS
(2022)
Article
Pharmacology & Pharmacy
David M. Stresser, Jun Sun, Sarah S. Wilson
Summary: An evaluation of an adult intestinal stem cell-derived organoid model for testing P450 induction in the gut was conducted. The results showed that human colon and ileal organoids exhibited different responses to several prototypical inducers compared to hepatocytes, indicating the potential for further development of this model as a physiologically relevant gut induction test system.
DRUG METABOLISM AND DISPOSITION
(2021)
Article
Toxicology
Sabine Gerbal-Chaloin, Philippe Briolotti, Martine Daujat-Chavanieu, Martin Kroyer Rasmussen
Summary: This study investigated the response of primary porcine hepatocytes (PPH) to standard CYP inducers, showing that PPH exhibited similar gene transcription responses to primary human hepatocytes (PHH) in some cases but differed in others.
CURRENT RESEARCH IN TOXICOLOGY
(2021)