Review
Biochemistry & Molecular Biology
Sabine Weber, Alexander L. Gerbes
Summary: Drug-induced liver injury (DILI) is a rare but potentially severe adverse drug event, which poses a major challenge for diagnosis in clinical practice and pharmacovigilance. Efforts have been made to establish diagnostic testing methods and biomarkers for safe diagnosis and differentiation from other liver diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Gastroenterology & Hepatology
Xiaoyun Li, Jieting Tang, Yimin Mao
Summary: The epidemiology and aetiology of drug-induced liver injury (DILI) vary across different countries and populations. Antibiotics are the leading cause of DILI in Western countries, while traditional Chinese medicine is the primary cause in Eastern countries. The incidence of hepatotoxicity induced by herbal and dietary supplements is increasing globally. Although several risk factors for DILI have been described, there are no confirmed risk factors for all-cause DILI.
LIVER INTERNATIONAL
(2022)
Review
Pharmacology & Pharmacy
Qihui Shao, Xinyu Mao, Zhixuan Zhou, Cong Huai, Zhiling Li
Summary: At present, most of the studies are mainly limited to CGS and GWAS, and there is still a long way to achieve clinical transformation. DNA methylation could be a new consideration, and ethnic differences and special populations also deserve attention.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Toxicology
Guillermo Quintas, Teresa Martinez-Sena, Isabel Conde, Eugenia Pareja Ibars, Jos Kleinjans, Jose Castell
Summary: DILI, an adverse toxic reaction associated with drug administration, is currently classified based on ALT and ALP values, but lacks accuracy. By integrating metabolomic information, a more accurate evaluation of DILI phenotypes can be achieved.
ARCHIVES OF TOXICOLOGY
(2021)
Article
Medicine, General & Internal
Dina Halegoua-DeMarzio, Victor Navarro, Jawad Ahmad, Bharathi Avula, Huiman Barnhart, A. Sidney Barritt, Herbert L. Bonkovsky, Robert J. Fontana, Marwan S. Ghabril, Jay H. Hoofnagle, Ikhlas A. Khan, David E. Kleiner, Elizabeth Phillips, Andrew Stolz, Raj Vuppalanchi
Summary: This case series study describes the clinical, histological, and HLA associations of turmeric-associated liver injury cases in the US Drug-Induced Liver Injury Network (DILIN). Ten cases of turmeric-associated liver injury were found, predominantly in women and with a strong linkage to HLA-B*35:01. Chemical analysis confirmed the presence of turmeric in all tested products. The study suggests an increasing trend of liver injury due to turmeric in the United States.
AMERICAN JOURNAL OF MEDICINE
(2023)
Review
Pharmacology & Pharmacy
Mirjana Stanic Benic, Lana Nezic, Vesna Vujic-Aleksic, Liliana Mititelu-Tartau
Summary: Many drugs can cause hepatotoxicity, and the treatment of drug-induced liver injury (DILI) is challenging. This study searched various databases to summarize the mechanisms, potential benefits, and adverse reactions of novel therapies for managing DILI. The evidence suggests that MgIG treatment may be effective in normalizing ALT levels, while bicyclol treatment may reduce ALT levels.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Pharmacology & Pharmacy
Anna Licata, Maria Giovanna Minissale, Simona Stankeviciute, Judith Sanabria-Cabrera, Maria Isabel Lucena, Raul J. Andrade, Piero Luigi Almasio
Summary: N-acetylcysteine (NAC) is an effective therapeutic option for acetaminophen (APAP) overdose, improving hepatotoxicity and reducing mortality. The timing of treatment initiation, within 8 to 24 hours after APAP overdose, is crucial for preventing or minimizing liver damage.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Oncology
Camille Houron, Marie Danielou, Olivier Mir, Bernard Fromenty, Gabriel Perlemuter, Cosmin Sebastian Voican
Summary: Multikinase inhibitors (MKI) have revolutionized cancer management, but there is a lack of data on MKI-related liver injury risk and clinical guidelines. Liver toxicity from MKI typically occurs one to two months after treatment initiation, with hepatocellular toxicity being more common. Early detection and monitoring of liver function are crucial for managing MKI-induced liver injury.
CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY
(2021)
Review
Medicine, Research & Experimental
Vicenc Ruiz de Porras, Mariona Figols, Albert Font, Eva Pardina
Summary: Chemotherapy-induced hepatotoxicity is a significant concern in cancer treatment, but curcumin has emerged as a potential strategy to mitigate this adverse effect. By targeting specific molecular mechanisms, curcumin exhibits anti-inflammatory, antioxidant, antifibrotic, and hypolipidemic properties that can help prevent and reduce chemotherapy-induced liver injury. Further clinical investigation is needed to demonstrate the efficacy of bioavailable curcumin formulations as hepatoprotective agents in cancer patients.
Article
Pharmacology & Pharmacy
Marja Driessen, Suzanne van der Plas-Duivesteijn, Anne S. Kienhuis, Evert-Jan van den Brandhof, Marianne Roodbergen, Bob van de Water, Herman P. Spaink, Magnus Palmblad, Leo T. M. van der Ven, Jeroen L. A. Pennings
Summary: The zebrafish embryo is a promising model for studying hepatotoxicity and could potentially reduce the use of rodents in such assessments. Proteomics analysis identified a set of potential protein markers for detecting adverse liver responses.
Article
Toxicology
Fernando Bessone, Antonella Ferrari, Nelia Hernandez, Manuel Mendizabal, Ezequiel Ridruejo, Alina Zerega, Federico Tanno, Maria Virginia Reggiardo, Julio Vorobioff, Hugo Tanno, Marco Arrese, Vinicius Nunes, Martin Tagle, Inmaculada Medina-Caliz, Mercedes Robles-Diaz, Hao Niu, Ismael Alvarez-Alvarez, Camilla Stephens, M. Isabel Lucena, Raul J. Andrade
Summary: In this study, the demographics, clinical characteristics, biochemical features, and outcome of nitrofurantoin-induced liver injury were described. The majority of the cases were women with a mean age of 61 years. Hepatocellular damage was the most common pattern of liver injury, and about half of the patients were asymptomatic. Most patients recovered within six months, but a small number developed nitrofurantoin-induced autoimmune-like hepatitis.
ARCHIVES OF TOXICOLOGY
(2023)
Review
Pharmacology & Pharmacy
Mercedes Robles-Diaz, Lana Nezic, Vesna Vujic-Aleksic, Einar S. Bjornsson
Summary: UDCA may have some benefits in the treatment and prevention of DILI according to available data, but a well designed RCT is needed to draw a firm conclusion on its efficacy in DILI.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Gastroenterology & Hepatology
Yi-Shin Huang, Ting-Tsung Chang, Cheng-Yuan Peng, Gin-Ho Lo, Chao-Wei Hsu, Chi-Tan Hu, Yi-Hsiang Huang
Summary: The study found that herbal and dietary supplements accounted for more than one-fifth of drug-induced liver injuries in Taiwan, and patients with HILI were more severe and had a higher mortality rate compared to those with CILI. Hepatitis B carriers, individuals with elevated baseline liver tests, and users of crude herbs may face a higher risk of HILI-related mortality. Prudent use of HDS is recommended for these high-risk individuals.
HEPATOLOGY INTERNATIONAL
(2021)
Article
Spectroscopy
Zhao Wang, Fan Zhang, Jianhua Xiong, Zhiqiang Mao, Zhihong Liu
Summary: This study developed a two-photon fluorescence probe for peroxynitrite, which can sensitively image ONOO- in mouse liver and demonstrate the potential application in DILI screening.
SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
(2021)
Review
Toxicology
Samantha Korver, Joanne Bowen, Kara Pearson, Raymond J. Gonzalez, Neil French, Kevin Park, Rosalind Jenkins, Christopher Goldring
Summary: DILI is a common adverse effect in drug therapy, with CK18 identified as a potential new biomarker for diagnosing early-stage DILI and providing insights into the mechanism of hepatocellular injury. However, further research is needed to characterize CK18 in preclinical models of DILI, particularly in vivo rat models.
ARCHIVES OF TOXICOLOGY
(2021)
Article
Medicine, Research & Experimental
Hasan Cagin Lenk, Robert Lovsletten Smith, Kevin S. O'Connell, Marin M. Jukic, Marianne Kristiansen Kringen, Ole A. Andreassen, Magnus Ingelman-Sundberg, Espen Molden
Summary: This study found that genetic variants in CYP1A and NFIB have a significant impact on the dose requirements and clinical response of clozapine, especially in smokers. Smokers carrying these genetic variants may require higher doses to achieve therapeutic effects.
CTS-CLINICAL AND TRANSLATIONAL SCIENCE
(2023)
Article
Genetics & Heredity
Valentin Skryabin, Ilya Rozochkin, Mikhail Zastrozhin, Volker Lauschke, Johan Franck, Evgeny Bryun, Dmitry Sychev
Summary: This meta-analysis suggests that pharmacogenetically guided dosing of antidepressants may increase treatment efficacy and significantly improve response and remission of patients.
PHARMACOGENOMICS JOURNAL
(2023)
Article
Cell Biology
Sara Redensek Trampuz, Sander van Riet, Asa Nordling, Magnus Ingelman-Sundberg
Summary: Connective tissue growth factor (CTGF) plays a role in regulating extracellular matrix (ECM) production and is elevated in liver fibrosis patients. In a 3D liver co-culture spheroid model, treatment with TGF-beta 1 or free fatty acids (FFA) increased the deposition of COL1A1 and expression of CTGF. Recombinant CTGF and angiotensin II also induced the expression of CTGF, TGF-beta 1, COL1A1, LOX, and IL-6. Silencing CTGF reduced COL1A1 deposition induced by both TGF-beta 1 and FFA. IL-6 was found to induce CTGF, COL1A1, and TGF-beta 1 production, suggesting its involvement in the CTGF-induced fibrosis pathway.
Review
Gastroenterology & Hepatology
Nayere Taebnia, Ute Romling, Volker M. Lauschke
Summary: Enteric bacterial infections are a major cause of disease and mortality worldwide, especially in developing countries. In vitro 2D monolayer cultures have provided valuable insights into the virulence mechanisms of various pathogens, leading to the discovery of potential targets for antimicrobial therapy and vaccines. More complex models, such as organoids, 3D bioengineered scaffolds, and microphysiological devices, have expanded our understanding of the effects of physiological and biological factors on infection. Advances in ex vivo cultures and intravital imaging have also allowed for the study of enteric pathogens on fluid secretion, barrier integrity, and immune cell surveillance. The combined use of these different methods promises to enhance our understanding of host-microbe interactions and their impact on intestinal health.
Article
Biochemistry & Molecular Biology
Claudia Tredup, Benardina Ndreshkjana, Natalie S. Schneider, Amelie Tjaden, Aurino M. Kemas, Sonia Youhanna, Volker M. Lauschke, Benedict-Tilman Berger, Andreas Kraemer, Lena M. Berger, Sandra Roehm, Stefan Knapp, Henner F. Farin, Susanne Mueller
Summary: Well-characterized small molecules are crucial for studying target proteins in biology and therapy. However, many compounds lack the necessary potency and selectivity for mechanistic cellular studies. The donated chemical probe (DCP) library provides an openly available collection of valuable and well-characterized tools, including a systematic description and comprehensive characterization data. It represents a unique resource for the biomedical research community.
ACS CHEMICAL BIOLOGY
(2023)
Article
Pharmacology & Pharmacy
Birgit M. Wollmann, Robert L. Smith, Marianne Kristiansen Kringen, Magnus Ingelman-Sundberg, Espen Molden, Elisabet Storset
Summary: This study aimed to investigate the correlation between solanidine metabolism and CYP2D6-mediated metabolism of risperidone in patients with known CYP2D6 genotypes. The results showed strong positive correlations between solanidine metabolism and CYP2D6-mediated risperidone metabolism.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2023)
Article
Pharmacology & Pharmacy
Katharina Kloditz, Eida Tewolde, Asa Nordling, Magnus Ingelman-Sundberg
Summary: During systemic inflammation, pro-inflammatory cytokines have significant effects on the expression of genes encoding drug metabolizing enzymes. A 3D liver spheroid model was used to study these effects and found that certain cytokines decrease the expression of CYP3A4 and UGT2B10, while increasing the expression of CYP2E1 and UGT1A3. Inhibitors of JAK1/2 were able to inhibit these cytokine-induced changes. These findings suggest that the 3D spheroid system is a versatile tool for studying drug metabolism under inflammatory conditions.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2023)
Article
Pharmacology & Pharmacy
Erkka Jarvinen, Helen S. Hammer, Oliver Poetz, Magnus Ingelman-Sundberg, Tore Bjerregaard Stage
Summary: The study assessed the usage of 3D spheroid primary human hepatocytes (PHHs) for studying the induction of important cytochrome P450 enzymes and drug transporters. The results showed that the 3D spheroid PHHs model can effectively investigate the mRNA and protein induction of hepatic drug-metabolizing enzymes and transporters, providing a solid basis for clinically relevant research.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2023)
Article
Biochemical Research Methods
Sonia Youhanna, Joseph Bruton, Kent Jardemark, Hakan Westerblad, Volker M. Lauschke
Summary: This article provides a protocol for isolating mouse primary skeletal muscle fibers using enzymatic dissociation or mechanical microdissection. The procedures for surgical removal of muscle tissue and isolation of intact single muscle fibers through collagenase digestion or mechanical microdissection are described in detail. The steps for intracellular calcium measurements and quantification using fluorescent measurement are also outlined. For complete details and execution of this protocol, please refer to the study by Gineste et al. (Reference 1).
Article
Biochemistry & Molecular Biology
Gisela Nilsson, Amin Mottahedin, Aura Zelco, Volker M. Lauschke, C. Joakim Ek, Juan Song, Maryam Ardalan, Sha Hua, Xiaoli Zhang, Carina Mallard, Henrik Hagberg, Jianmei W. Leavenworth, Xiaoyang Wang
Summary: The two isoforms of OPN, sOPN and iOPN, have different roles in myelination and axonal integrity. Deficiency of these isoforms leads to abnormal myelination and axonal degeneration.
Article
Engineering, Biomedical
Milan Finn Wesseler, Nayere Taebnia, Sean Harrison, Sonia Youhanna, Lena C. Preiss, Aurino M. Kemas, Akos Vegvari, Jaroslav Mokry, Gareth J. Sullivan, Volker M. Lauschke, Niels B. Larsen
Summary: This study presents an accurate liver microphysiological system (MPS) created through engineering of 3D printed hydrogel chips with synthetic vasculature channels. The MPS allows the long-term culture of human liver cells and demonstrates improved molecular phenotypes compared to other 3D culture methods. The platform also successfully generates physiologically relevant oxygen gradients and shows zonation-specific toxicity patterns.
ACTA BIOMATERIALIA
(2023)
Article
Pharmacology & Pharmacy
Nuria Oliva-Vilarnau, Sabine U. Vorrink, Florian A. Buettner, Timo Heinrich, Janike Sensbach, Isabel Koscielski, Dirk Wienke, Carl Petersson, Dominique Perrin, Volker M. Lauschke
Summary: This study tested the induction potential of various YAP/TEAD inhibitors with different modes of action and TEAD isoform selectivity profiles on CYP in primary human hepatocytes. The results showed that YAP/TEAD inhibition can broadly induce CYP in 2D monolayers, but only marginally in 3D spheroids. RNA-Seq analysis revealed increased YAP/TEAD signaling in 2D culture, along with elevated activities of the interacting transcription factors LXR and ESRRA. Inhibition of YAP/TEAD hyperactivation reduced hepatocyte dedifferentiation and increased hepatic functionality.
BIOCHEMICAL PHARMACOLOGY
(2023)
Review
Pharmacology & Pharmacy
Roman Tremmel, Sebastian Pirmann, Yitian Zhou, Volker M. Lauschke
Summary: The development of sequencing technologies has enabled the study of human genomic variations. Pharmacogenes, which are known to be highly polymorphic, have been extensively studied, but the majority of the identified variants remain unknown in terms of their impact. It is crucial to develop tools and frameworks to accurately infer the effects of pharmacogenomic variants and incorporate them into personalized drug response predictions.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2023)
Article
Endocrinology & Metabolism
Lipeng Ren, Jeremie Charbord, Lianhe Chu, Aurino M. Kemas, Maria Bertuzzi, Jiarui Mi, Chen Xing, Volker M. Lauschke, Olov Andersson
Summary: Adjudin promotes functional maturation of immature islets, improves function of dysfunctional islets, stimulates glucose uptake in the liver, and improves glucose homeostasis in diabetic mice.
Letter
Pharmacology & Pharmacy
Magnus Ingelman-Sundberg, Marin Jukic, Line Skute Braten, Marianne Kristiansen Kringen, Espen Molden
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2023)