Review
Cell Biology
Sydney Stern, Hongbing Wang, Nakissa Sadrieh
Summary: Drug-induced liver injury (DILI) is a major concern in the pharmaceutical industry and global health due to its high attrition rates and complex pathogenesis. In vitro co-culture models that incorporate the immune system have shown promise in investigating idiosyncratic DILI (iDILI). Human-based 3D multicellular models have been developed to mimic the hepatic microenvironment and provide a more accurate representation of iDILI. However, more research is needed to harmonize and compare the characteristics of these models, as well as address challenges such as disease-related endpoints and multi-cellular mechanisms.
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)
Article
Pharmacology & Pharmacy
James J. Beaudoin, Kyunghee Yang, Jeffry Adiwidjaja, Guncha Taneja, Paul B. Watkins, Scott Q. Siler, Brett A. Howell, Jeffrey L. Woodhead
Summary: Inhibition of MDR3 leads to cholestatic drug-induced liver injury by disrupting bile flow and damaging the biliary epithelium. This is caused by a reduction in phospholipid excretion, which decreases the formation of mixed micelles in the bile duct and results in an excess of free bile acids that can damage the bile duct epithelial cells. Cholangiocytes can compensate for increased bile acid levels via the cholehepatic shunt pathway or bicarbonate secretion, influencing viability and toxicity.
FRONTIERS IN PHARMACOLOGY
(2023)
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
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
Biochemistry & Molecular Biology
Alison Jee, Samantha Christine Sernoskie, Jack Uetrecht
Summary: IDILI remains a significant problem for patients and drug development due to its idiosyncratic nature. Most cases of IDILI are likely caused by reactive metabolites of drugs and mediated by the adaptive immune system, with some associations with specific human leukocyte antigen haplotypes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Chemistry, Medicinal
Kyunghee Yang, Cen Guo, Jeffrey L. Woodhead, Robert L. St Claire, Paul B. Watkins, Scott Q. Siler, Brett A. Howell, Kim L. R. Brouwer
JOURNAL OF PHARMACEUTICAL SCIENCES
(2016)
Article
Toxicology
Jeffrey L. Woodhead, William J. Brock, Sharin E. Roth, Susan E. Shoaf, Kim L. R. Brouwer, Rachel Church, Tom N. Grammatopoulos, Linsey Stiles, Scott Q. Siler, Brett A. Howell, Merrie Mosedale, Paul B. Watkins, Lisl K. M. Shoda
TOXICOLOGICAL SCIENCES
(2017)
Article
Medicine, Research & Experimental
Jeffrey L. Woodhead, Franziska Paech, Martina Maurer, Marc Engelhardt, Anne H. Schmitt-Hoffmann, Jochen Spickermann, Simon Messner, Mathias Wind, Anne-Therese Witschi, Stephan Kraehenbuehl, Scott Q. Siler, Paul B. Watkins, Brett A. Howell
CTS-CLINICAL AND TRANSLATIONAL SCIENCE
(2018)
Article
Toxicology
Christina Battista, Kyunghee Yang, Simone H. Stahl, Jerome T. Mettetal, Paul B. Watkins, Scott Q. Siler, Brett A. Howell
TOXICOLOGICAL SCIENCES
(2018)
Article
Toxicology
Diane M. Longo, Jeffrey L. Woodhead, Paul Walker, Krisztina Heredi-Szabo, Karoly Mogyorosi, Francis S. Wolenski, Yvonne P. Dragan, Merrie Mosedale, Scott Q. Siler, Paul B. Watkins, Brett A. Howell
TOXICOLOGICAL SCIENCES
(2019)
Article
Chemistry, Multidisciplinary
Jeffrey L. Woodhead, Kyunghee Yang, David Oldach, Chris MacLauchlin, Prabhavathi Fernandes, Paul B. Watkins, Scott Q. Siler, Brett A. Howell
PHARMACEUTICAL RESEARCH
(2019)
Article
Toxicology
Diane M. Longo, Lisl K. M. Shoda, Brett A. Howell, Vladimir Coric, Robert M. Berman, Irfan A. Qureshi
TOXICOLOGICAL SCIENCES
(2020)
Article
Toxicology
Brenda Smith, Josh Rowe, Paul B. Watkins, Messoud Ashina, Jeffrey L. Woodhead, Frank D. Sistare, Peter J. Goadsby
TOXICOLOGICAL SCIENCES
(2020)
Article
Medicine, Legal
Gary Eichenbaum, Kyunghee Yang, Yeshitila Gebremichael, Brett A. Howell, F. Jay Murray, David Jacobson-Kram, Hartmut Jaeschke, Edwin Kuffner, Cathy K. Gelotte, John C. K. Lai, Daniele Wikoff, Evren Atillasoy
REGULATORY TOXICOLOGY AND PHARMACOLOGY
(2020)
Review
Medicine, Legal
F. Jay Murray, Andrew D. Monnot, David Jacobson-Kram, Samuel M. Cohen, Jerry F. Hardisty, Suren B. Bandara, Michael Kovochich, Milind Deore, Suresh Kumar Pitchaiyan, Cathy K. Gelotte, John C. K. Lai, Evren Atillasoy, Anne Hermanowski-Vosatka, Edwin Kuffner, Kenneth M. Unice, Kyunghee Yang, Yeshitila Gebremichael, Brett A. Howell, Gary Eichenbaum
REGULATORY TOXICOLOGY AND PHARMACOLOGY
(2020)
Article
Pharmacology & Pharmacy
Grant Generaux, Vinal V. Lakhani, Yuching Yang, Sashi Nadanaciva, Luping Qiu, Keith Riccardi, Li Di, Brett A. Howell, Scott Q. Siler, Paul B. Watkins, Hugh A. Barton, Michael D. Aleo, Lisl K. M. Shoda
PHARMACOLOGY RESEARCH & PERSPECTIVES
(2019)
Article
Pharmacology & Pharmacy
D. M. Longo, G. T. Generaux, B. A. Howell, S. Q. Siler, D. J. Antoine, D. Button, A. Caggiano, A. Eisen, J. Iaci, R. Stanulis, T. Parry, M. Mosedale, P. B. Watkins
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2017)
Article
Toxicology
Franziska Paech, Simon Messner, Jochen Spickermann, Mathias Wind, Anne-Hortense Schmitt-Hoffmann, Anne Therese Witschi, Brett A. Howell, Rachel J. Church, Jeff Woodhead, Marc Engelhardt, Stephan Krahenbuhl, Martina Maurer
ARCHIVES OF TOXICOLOGY
(2017)
Article
Genetics & Heredity
Lisl K. M. Shoda, Christina Battista, Scott Q. Siler, David S. Pisetsky, Paul B. Watkins, Brett A. Howell
GENE REGULATION AND SYSTEMS BIOLOGY
(2017)
Review
Pharmacology & Pharmacy
Jeffrey L. Woodhead, Paul B. Watkins, Brett A. Howell, Scott Q. Siler, Lisl K. M. Shoda
DRUG METABOLISM AND PHARMACOKINETICS
(2017)