Liver Toxicity
Liver Toxicity - Related Videos
11:06
Human Liver Microphysiological System for Assessing Drug-Induced Liver Toxicity In Vitro
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Cited by 11 •
2022
Drug-induced liver injury (DILI) is a major cause of drug failure. A protocol has been developed to accurately predict the DILI liability of a compound using a liver microphysiological system (MPS). The liver model uses the coculture of primary hepatic cells and translationally relevant endpoints to assess cellular responses to treatment.
09:49
Kupffer Cell Isolation for Nanoparticle Toxicity Testing
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Cited by 28 •
2015
Liver macrophages, named Kupffer cells, are responsible for the capture of circulating nanoparticles. We describe here a method, of high cell purity and yield, for Kupffer cell isolation. The modified LDH assay is used here to measure the toxicity induced by carbon nanotubes in Kupffer cells.
12:35
In vivo Liver Endocytosis Followed by Purification of Liver Cells by Liver Perfusion
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Cited by 14 •
2011
The study of liver sinusoidal endothelial cells (SECs) must be performed with primary cells obtained from the animal as no cell lines exist. This method relies on liver digestion and differential centrifugation for SEC purification for subsequent culturing and experimentation.
12:13
Ex Situ Normothermic Machine Perfusion of Donor Livers
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Cited by 21 •
2015
Here we present a protocol describing oxygenated ex situ machine perfusion of donor liver grafts. This article contains a step by step protocol to procure and prepare the liver graft for machine perfusion, prepare the perfusion fluid, prime the perfusion machine and perform oxygenated normothermic machine perfusion of the liver graft.
09:24
Decellularization and Recellularization of Whole Livers
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Cited by 39 •
2011
Perfusion decellularization is a novel technique to produce whole liver scaffolds that retains the organ's extracellular matrix composition and microarchitecture. Herein, the method of preparing whole organ scaffolds using perfusion decellularization and subsequent repopulation with hepatocytes is described. Functional and transplantable liver grafts can be generated using this technique.
FAQs
Reactive metabolites can form when the liver metabolizes a drug or chemical, and they may initiate oxidative stress, mitochondrial dysfunction, inflammation, or immune-mediated damage. These mechanisms can impair hepatic cells and function even when the original compound is less damaging. Identifying metabolite-related injury helps pharmacologists explain adverse reactions and recognize compounds that require closer safety evaluation.
Hepatocellular injury primarily reflects damage to liver cells, whereas cholestasis represents impaired bile movement or handling. These patterns provide different descriptions of how an exposure affects the liver and help organize findings from biochemical testing, histopathology, and clinical monitoring. Distinguishing them supports more precise interpretation of drug safety results during development and patient care.
Oxidative stress and mitochondrial dysfunction can connect drug metabolism with impaired hepatic function. Reactive chemical products may promote oxidative damage, while mitochondrial disruption can further compromise cellular performance and contribute to injury. Considering these mechanisms helps researchers interpret toxicity findings beyond a single laboratory value and supports evaluation of how candidate compounds may produce dose-related risks.
A reliable evaluation combines biochemical biomarkers, cellular models, animal models, histopathology, and clinical monitoring of liver enzymes. Biomarkers provide measurable evidence of injury, models help investigate effects under controlled conditions, and histopathology examines tissue changes. Clinical enzyme monitoring adds patient-level information, allowing investigators to compare experimental findings with potential adverse drug reactions.
Assessment begins with testing candidate compounds using cellular and animal models, followed by measurement of biochemical biomarkers and examination of tissue through histopathology. Researchers then integrate these findings with clinical monitoring of liver enzymes as development progresses. This staged approach can reveal hazardous compounds, clarify dose-related risks, and inform decisions about safer therapeutic design.
It is important throughout drug development and after treatment reaches patients, because hepatic injury can affect both compound selection and clinical safety. Early testing helps identify hazardous candidates before further development, while clinical monitoring supports timely detection of adverse drug reactions. The combined evidence can guide safer therapeutic design and improve recognition of treatment-associated liver effects.
These studies can identify hazardous compounds, characterize whether findings align with hepatocellular injury or cholestasis, and clarify risks related to exposure or dose. Results from biomarkers, models, histopathology, and liver-enzyme monitoring help investigators decide which candidates need modification or closer observation. Ultimately, the evidence supports safer therapeutic design and more timely responses to adverse reactions.