Auriculatone Sulfate Effectively Protects Mice Against Acetaminophen-Induced Liver Injury

Acetaminophen (APAP) overdose is very common worldwide and has been widely recognized as the leading cause of drug-induced liver injury in the Western world. In our previous investigation, auriculatone, a natural product firstly obtained from Aster auriculatus, has demonstrated a potent protective effect against APAP-induced hepatotoxicity in HL-7702 cells. However, the poor water solubility and low bioavailability restrict its application. Auriculatone sulfate (AS) is a sulfated derivative of auriculatone with highly improved water-solubility. Hepatoprotective effects against APAP-induced liver injury (AILI) showed that intragastric pretreatment with AS at 50 mg/kg almost completely prevented mice against APAP-induced increases of serum alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase and ATPase. Histological results showed that AS could protect the liver tissue damage. In addition, AS pretreatment not only significantly retained hepatic malondialdehyde and the activities of glutathione, superoxide dismutase, and glutathione peroxidase at normal levels, but also markedly suppressed the increase of pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 levels in mouse liver caused by overdose APAP. Immunohistochemical analysis showed that AS obviously attenuated the expression of CD45 and HNE in liver tissue. Further mechanisms of action investigation showed that inhibition of cytochrome P450 3A11 (CYP 3A11) and CYP2E1 enzymatic activities (but not that of CYP1A2) was responsible for APAP bioactivation. In conclusion, AS showed a hepatoprotective effect against AILI through alleviating oxidative stress and inflammation and inhibiting CYP-mediated APAP bioactivation. It may be an effective hepatoprotective agent for AILI and other forms of human liver disease.

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Acetaminophen Test Battery (ATB): A Comprehensive Method to Study Acetaminophen-Induced Acute Liver Injury

Gene Expression ◽

10.3727/105221620x15901763757677 ◽

2020 ◽

Vol 20 (2) ◽

pp. 125-138 ◽

Cited By ~ 2

Author(s):

Bharat Bhushan ◽

Udayan Apte

Keyword(s):

Liver Injury ◽

Acute Liver Injury ◽

Test Battery ◽

Western World ◽

Drug Induced ◽

Technical Problems ◽

Drug Induced Liver Injury ◽

Comprehensive Method ◽

Injury Models ◽

Apap Hepatotoxicity

Acetaminophen (APAP) overdose is the major cause of acute liver failure (ALF) in the Western world. Extensive research is ongoing to identify the mechanisms of APAP-induced ALF. APAP-induced acute liver injury is also one of the most commonly studied drug-induced liver injury models in the field of hepatotoxicity. APAP toxicity is triphasic and includes three mechanistically interlinked but temporally distinct phases of initiation, progression, and recovery/regeneration. Despite how commonly it is studied, the methods to study APAP toxicity differ significantly, often leading to confusing and contradictory data. There are number of reviews on mechanisms of APAP toxicity, but a detailed mechanism-based comprehensive method and list of assays that covers all phases of APAP hepatotoxicity are missing. The goal of this review is to provide a standard protocol and guidelines to study APAP toxicity in mice including a test battery that can help investigators to comprehensively analyze APAP toxicity in the specific context of their hypothesis. Further, we will identify the major roadblocks and common technical problems that can significantly affect the results. This acetaminophen test battery (ATB) will be an excellent guide for scientists studying this most common and clinically relevant drug-induced liver injury and will also be helpful as a roadmap for hypothesis development to study novel mechanisms.

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Analysis of IL-10, IL-4 and TNF-α polymorphisms in drug-induced liver injury (DILI) and its outcome

Journal of Hepatology ◽

10.1016/j.jhep.2008.03.017 ◽

2008 ◽

Vol 49 (1) ◽

pp. 107-114 ◽

Cited By ~ 56

Author(s):

Ketevan Pachkoria ◽

M. Isabel Lucena ◽

Esperanza Crespo ◽

Francisco Ruiz-Cabello ◽

Susana Lopez-Ortega ◽

...

Keyword(s):

Liver Injury ◽

Drug Induced ◽

Drug Induced Liver Injury ◽

Tnf Α

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Drug-induced Liver Injury Due to a Horse Chestnut Dietary Supplement

European Journal of Case Reports in Internal Medicine ◽

10.12890/2021_002389 ◽

2021 ◽

Author(s):

Diogo Costa Santos ◽

Graça Lérias ◽

Isabel Madruga

Keyword(s):

Liver Injury ◽

Dietary Supplements ◽

Venous Insufficiency ◽

Acute Liver Injury ◽

Western World ◽

Horse Chestnut ◽

Drug Induced ◽

Common Cause ◽

Drug Induced Liver Injury ◽

Clinically Significant

Drug-induced liver injury (DILI) is the most common cause of acute liver failure in the Western world. In recent years, natural herbal and dietary supplements have become widely available to the general public and have increased in popularity. Reports of idiosyncratic liver injury caused by such supplements have also increased over the last decade. Horse chestnut is a herb used in dietary supplements primarily for complications of venous insufficiency. Clinically significant acute liver injury has been very rarely associated with its use. We present the case of a 70-year-old man with idiosyncratic horse chestnut-induced liver injury.

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Corrigendum to “Analysis of IL-10, IL-4 and TNF-α polymorphisms in drug-induced liver injury (DILI) and its outcome” [J Hepatol 49 (2008) 107–114]

Journal of Hepatology ◽

10.1016/j.jhep.2009.01.001 ◽

2009 ◽

Vol 50 (3) ◽

pp. 636 ◽

Cited By ~ 1

Author(s):

Ketevan Pachkoria ◽

M. Isabel Lucena ◽

Esperanza Crespo ◽

Francisco Ruiz-Cabello ◽

Susana Lopez-Ortega ◽

...

Keyword(s):

Liver Injury ◽

Drug Induced ◽

Drug Induced Liver Injury ◽

Tnf Α

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Development and Validation of a Highly Sensitive LC-MS/MS Method for the Analysis of Bile Acids in Serum, Plasma, and Liver Tissue Samples

Metabolites ◽

10.3390/metabo10070282 ◽

2020 ◽

Vol 10 (7) ◽

pp. 282

Author(s):

Cristina Gómez ◽

Simon Stücheli ◽

Denise V. Kratschmar ◽

Jamal Bouitbir ◽

Alex Odermatt

Keyword(s):

Bile Acid ◽

Liver Injury ◽

Bile Acids ◽

Liver Tissue ◽

Bioactive Molecules ◽

Rodent Species ◽

Drug Induced ◽

Tissue Samples ◽

Drug Induced Liver Injury ◽

Bile Acid Profiles

Bile acids control lipid homeostasis by regulating uptake from food and excretion. Additionally, bile acids are bioactive molecules acting through receptors and modulating various physiological processes. Impaired bile acid homeostasis is associated with several diseases and drug-induced liver injury. Individual bile acids may serve as disease and drug toxicity biomarkers, with a great demand for improved bile acid quantification methods. We developed, optimized, and validated an LC-MS/MS method for quantification of 36 bile acids in serum, plasma, and liver tissue samples. The simultaneous quantification of important free and taurine- and glycine-conjugated bile acids of human and rodent species has been achieved using a simple workflow. The method was applied to a mouse model of statin-induced myotoxicity to assess a possible role of bile acids. Treatment of mice for three weeks with 5, 10, and 25 mg/kg/d simvastatin, causing adverse skeletal muscle effects, did not alter plasma and liver tissue bile acid profiles, indicating that bile acids are not involved in statin-induced myotoxicity. In conclusion, the established LC-MS/MS method enables uncomplicated sample preparation and quantification of key bile acids in serum, plasma, and liver tissue of human and rodent species to facilitate future studies of disease mechanisms and drug-induced liver injury.

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Evaluation of 3-D bioprinted human liver tissue for assessment drug-induced liver injury across a diverse set of chemical classes

Toxicology Letters ◽

10.1016/j.toxlet.2017.07.954 ◽

2017 ◽

Vol 280 ◽

pp. S270

Author(s):

Jeffrey Irelan ◽

Candace Crogan-Grundy ◽

Ryan Smith ◽

Rhiannon Hardwick ◽

Deborah Nguyen

Keyword(s):

Liver Injury ◽

Liver Tissue ◽

Human Liver ◽

Drug Induced ◽

Human Liver Tissue ◽

Drug Induced Liver Injury

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Hepatitis E Virus Detection in Liver Tissue from Patients with Suspected Drug-Induced Liver Injury

Frontiers in Medicine ◽

10.3389/fmed.2015.00020 ◽

2015 ◽

Vol 2 ◽

Cited By ~ 2

Author(s):

Obinna Chijioke ◽

Marion Bawohl ◽

Erik Springer ◽

Achim Weber

Keyword(s):

Liver Injury ◽

Liver Tissue ◽

Hepatitis E Virus ◽

Virus Detection ◽

Hepatitis E ◽

Suspected Drug ◽

Drug Induced ◽

Drug Induced Liver Injury

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Leberschaden unter oraler Antikoagulation, Statin- und ACE-Hemmertherapie

Praxis ◽

10.1024/1661-8157/a000298 ◽

2010 ◽

Vol 99 (21) ◽

pp. 1259-1265 ◽

Cited By ~ 2

Author(s):

Bruggisser ◽

Terraciano ◽

Rätz Bravo ◽

Haschke

Keyword(s):

Liver Injury ◽

Wird Eine ◽

Drug Induced ◽

Drug Induced Liver Injury

Ein 71-jähriger Patient stellt sich mit Epistaxis und ikterischen Skleren auf der Notfallstation vor. Der Patient steht unter einer Therapie mit Phenprocoumon, Atorvastatin und Perindopril. Anamnestisch besteht ein langjähriger Alkoholabusus. Laborchemisch werden massiv erhöhte Leberwerte (ALAT, Bilirubin) gesehen. Der INR ist unter oraler Antikoagulation und bei akuter Leberinsuffizienz >12. Die weiterführenden Abklärungen schliessen eine Virushepatitis und eine Autoimmunhepatitis aus. Nachdem eine Leberbiopsie durchgeführt werden kann, wird eine medikamentös-toxische Hepatitis, ausgelöst durch die Komedikation von Atorvastatin, Phenprocoumon und Perindopril bei durch Alkohol bereits vorgeschädigter Leber diagnostiziert. Epidemiologie, Pathophysiologie und Klink der medikamentös induzierten Leberschäden (drug induced liver injury, DILI), speziell von Coumarinen, Statinen und ACE-Hemmern werden im Anschluss an den Fallbericht diskutiert.

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