scholarly journals Screening for Susceptibility-Related Biomarkers of Diclofenac-Induced Liver Injury in Rats Using Metabolomics

2021 ◽  
Vol 12 ◽  
Author(s):  
Can Tu ◽  
Yuan Gao ◽  
Di Song ◽  
Ming Niu ◽  
Run-ran Ma ◽  
...  
Keyword(s):  
Liver Injury ◽  
Inflammatory Responses ◽  
Underlying Mechanism ◽  
Drug Induced ◽  
Over The Counter ◽  
Receiver Operating Characteristic Curves ◽  
Drug Induced Liver Injury ◽  
Unmet Demand ◽  
Diagnostic Capabilities ◽  
Acute Phase Reactions

Early identification of individuals susceptible to idiosyncratic drug-induced liver injury (IDILI) is a challenging unmet demand. Diclofenac, one of the most widely available over-the-counter drugs for pain management worldwide, may induce liver dysfunction, acute liver failure, and death. Herein, we report that diclofenac-related hepatobiliary adverse reactions occurred more frequently in cases with immune activation. Furthermore, experiments with rats demonstrated divergent hepatotoxicity responses in individuals exposed to diclofenac, and modest inflammation potentiated diclofenac-induced liver injury. Susceptible rats had unique plasma metabolomic characteristics, and as such, the metabolomic approach could be used to distinguish susceptible individuals. The 23 identified susceptibility-related metabolites were enriched by several metabolic pathways related to acute-phase reactions of immunocytes and inflammatory responses, including sphingolipid, tyrosine, phenylalanine, tryptophan, and lipid metabolism pathways. This finding implies a mechanistic role of metabolic and immune disturbances affects susceptibility to diclofenac-IDILI. Further nine metabolite biomarkers with potent diagnostic capabilities were identified using receiver operating characteristic curves. These findings elucidated the potential utility of metabolomic biomarkers to identify individuals susceptible to drug hepatotoxicity and the underlying mechanism of metabolic and immune disturbances occurring in IDILI.

Ginsenoside Rb1, A Major Saponin from Panax ginseng, Exerts Protective Effects Against Acetaminophen-Induced Hepatotoxicity in Mice

2019 ◽  
Vol 47 (08) ◽  
pp. 1815-1831 ◽  
Author(s):  
Shen Ren ◽  
Jing Leng ◽  
Xing-Yue Xu ◽  
Shuang Jiang ◽  
Ying-Ping Wang ◽  
...  
Keyword(s):  
Liver Injury ◽  
Panax Ginseng ◽  
Inflammatory Responses ◽  
Interleukin 1 ◽  
Protective Effects ◽  
Ginsenoside Rb1 ◽  
Drug Induced ◽  
Drug Induced Liver Injury ◽  
Oxide Synthase

Acute liver injury (ALI) induced by acetaminophen (APAP) is the main cause of drug-induced liver injury. Previous reports indicated liver failure could be alleviated by saponins (ginsenosides) from Panax ginseng against APAP-induced inflammatory responses in vivo. However, validation towards ginsenoside Rb1 as a major and marker saponin may protect liver from APAP-induced ALI and its mechanisms are poorly elucidated. In this study, the protective effects and the latent mechanisms of Rb1 action against APAP-induced hepatotoxicity were investigated. Rb1 was administered orally with 10[Formula: see text]mg/kg and 20[Formula: see text]mg/kg daily for 1 week before a single injection of APAP (250[Formula: see text]mg/kg, i.p.) 1[Formula: see text]h after the last treatment of Rb1. Serum alanine/aspartate aminotransferases (ALT/AST), liver glutathione (GSH) depletion, as well as the inflammatory cytokines, such as tumor necrosis factor-[Formula: see text] (TNF-[Formula: see text]), interleukin-1[Formula: see text] (IL-1[Formula: see text]), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2), were analyzed to indicate the underlying protective effects of Rb1 against APAP-induced hepatotoxicity with significant inflammatory responses. Histological examination further proved Rb1’s protective effects. Importantly, Rb1 mitigated the changes in the phosphorylation of MAPK and PI3K/Akt, as well as its downstream factor NF-[Formula: see text]B. In conclusion, experimental data clearly demonstrated that Rb1 exhibited a remarkable liver protective effect against APAP-induced ALI, partly through regulating MAPK and PI3K/Akt signaling pathways-mediated inflammatory responses.

scholarly journals Menotrophin Induced Autoimmune Hepatitis

2019 ◽  
Vol 2019 ◽  
pp. 1-4 ◽  
Author(s):  
Shurouq H. Alqrinawi ◽  
Nuralhuda Akbar ◽  
Hind AlFaddag ◽  
Shahrazad Akbar ◽  
Lujayn Akbar ◽  
...  
Keyword(s):  
Liver Injury ◽  
Autoimmune Hepatitis ◽  
Plasma Cells ◽  
Caucasian Woman ◽  
Drug Induced ◽  
Over The Counter ◽  
Drug Induced Liver Injury ◽  
First Case ◽  
Igg Level ◽  
New Onset

Menotrophin is a protein-based hormonal therapy. It is used as a fertility medication that is given as injection either subcutaneously or intramuscularly. Menotrophin has not been previously reported to cause drug-induced liver injury. Drug-induced liver injury (DILI) is commonly seen nowadays with the expansion of the drug industry. It is associated with prescribed medications, over the counter drugs, herbal and dietary supplements. We report the first case of Menotrophin-induced autoimmune hepatitis in a 26-year-old Caucasian woman who was diagnosed with primary infertility due to failure to conceive after five years of marriage. She had received several cycles of Menotrophin, then developed new onset jaundice and fatigue associated with increase in transaminases. She had normal baseline liver function and enzymes prior to receiving treatment with Menotrophin. Evaluation showed no evidence of viral hepatitis, metabolic, alcoholic or vascular causes of liver injury. Autoimmune screening was positive for antinuclear antibody (ANA) with titer of 1 : 640 fine speckled, immunoglobulin G (IgG) level was 1900 mg/dl. Antimitochondrial antibodies (AMA) and antismooth muscle antibodies were negative. Liver biopsy showed features of chronic hepatitis with interface hepatitis and prominence of plasma cells, which best reflects autoimmune hepatitis. Her liver enzymes and bilirubin completely normalized after discontinuation of further Menotrophin therapy and starting treatment with prednisolone and Azathioprine.

scholarly journals A Case of Severe Drug-induced Liver Injury Caused by Over the Counter Herb (Cinnamon): Review of Literature

2018 ◽  
Vol 8 (2) ◽  
pp. 167-171
Author(s):  
Masanori Abe ◽  
Morikazu Onji ◽  
Takahide Uehara ◽  
Jiro Miyaike ◽  
Masaki Oomoto ◽  
...  
Keyword(s):  
Liver Injury ◽  
Review Of Literature ◽  
Drug Induced ◽  
Over The Counter ◽  
Drug Induced Liver Injury

scholarly journals Chinese Skullcap in Move Free Arthritis Supplement Causes Drug Induced Liver Injury and Pulmonary Infiltrates

2013 ◽  
Vol 2013 ◽  
pp. 1-4 ◽  
Author(s):  
Renumathy Dhanasekaran ◽  
Victoria Owens ◽  
William Sanchez
Keyword(s):  
Liver Injury ◽  
Case Reports ◽  
Pulmonary Complications ◽  
Adverse Outcomes ◽  
Medical Community ◽  
Temporal Association ◽  
Drug Induced ◽  
Over The Counter ◽  
Drug Induced Liver Injury ◽  
Pulmonary Infiltrates

Herbal medications are being increasingly used by the American population especially for common conditions like arthritis. They have been reported to cause adverse effects, including significant hepatotoxicity, but reporting remains sporadic. We report here a patient who developed drug induced liver injury following the intake of Move Free, which is an over-the-counter arthritis supplement. We propose that Chinese skullcap, which is one of the herbal ingredients of the medication, is responsible for the adverse event. There was a strong temporal association between the intake of supplement and onset of symptoms, and also there have been a few recent case reports implicating the same component. A unique observation in our case is the occurrence of pulmonary infiltrates simultaneously with the hepatotoxicity, and this side effect has not been well documented before. Both the hepatic and pulmonary complications completely resolved over few weeks after the patient stopped taking the medication. Since these supplements are readily available over the counter, we feel that it is important to document possible adverse outcomes to raise awareness in the medical community and also among patients.

scholarly journals Serum Metabolomic Analysis of Chronic Drug-Induced Liver Injury With or Without Cirrhosis

2021 ◽  
Vol 8 ◽  
Author(s):  
Shuai-shuai Chen ◽  
Ying Huang ◽  
Yu-ming Guo ◽  
Shan-shan Li ◽  
Zhuo Shi ◽  
...  
Keyword(s):  
Liver Injury ◽  
Tricarboxylic Acid Cycle ◽  
Area Under The Curve ◽  
Underlying Mechanism ◽  
Metabolic Reprogramming ◽  
Decompensated Cirrhosis ◽  
Drug Induced ◽  
Drug Induced Liver Injury ◽  
Metabolic Fingerprint ◽  
Auc Value

Background: Chronic drug-induced liver injury (DILI) occurs in up to 20% of all DILI patients. It presents a chronic pattern with persistent or relapsed episodes and may even progress to cirrhosis. However, its underlying development mechanism is poorly understood.Aims: To find serum metabolite signatures of chronic DILI with or without cirrhosis, and to elucidate the underlying mechanism.Methods: Untargeted metabolomics coupled with pattern recognition approaches were used to profile and extract metabolite signatures from 83 chronic DILI patients, including 58 non-cirrhosis (NC) cases, 14 compensated cirrhosis (CC) cases, and 11 decompensated cirrhosis (DC) cases.Results: Of the 269 annotated metabolites associated with chronic DILI, metabolic fingerprints associated with cirrhosis (including 30 metabolites) and decompensation (including 25 metabolites), were identified. There was a significantly positive correlation between cirrhosis-associated fingerprint (eigenmetabolite) and the aspartate aminotransferase-to-platelet ratio index (APRI) (r = 0.315, P = 0.003). The efficacy of cirrhosis-associated eigenmetabolite coupled with APRI to identify cirrhosis from non-cirrhosis patients was significantly better than APRI alone [area under the curve (AUC) value 0.914 vs. 0.573]. The decompensation-associated fingerprint (eigenmetabolite) can effectively identify the compensation and decompensation periods (AUC value 0.954). The results of the metabolic fingerprint pathway analysis suggest that the blocked tricarboxylic acid cycle (TCA cycle) and intermediary metabolism, excessive accumulation of bile acids, and perturbed amino acid metabolism are potential mechanisms in the occurrence and development of chronic DILI-associated cirrhosis.Conclusions: The metabolomic fingerprints characterize different stages of chronic DILI progression and deepen the understanding of the metabolic reprogramming mechanism of chronic DILI progression to cirrhosis.

scholarly journals A patient with Gilbert's syndrome complicated with drug-induced liver injury by the over-the-counter drug and Fluvastatin Sodium: A case report

Kanzo ◽  
2009 ◽  
Vol 50 (3) ◽  
pp. 139-144
Author(s):  
Minoru Ayada ◽  
Tetsuya Ishikawa ◽  
Akihiko Okumura ◽  
Naoki Hotta ◽  
Akinori Hirose ◽  
...  
Keyword(s):  
Case Report ◽  
Liver Injury ◽  
Drug Induced ◽  
Over The Counter ◽  
Gilbert’S Syndrome ◽  
Drug Induced Liver Injury ◽  
Gilbert's Syndrome

scholarly journals Drug-induced Liver Injury with Serious Multiform Exudative Erythema following the Use of an Over-the-counter Medication Containing Ibuprofen

2015 ◽  
Vol 54 (4) ◽  
pp. 395-399 ◽  
Author(s):  
Takao Watanabe ◽  
Masanori Abe ◽  
Fujimasa Tada ◽  
Kanako Aritomo ◽  
Hironori Ochi ◽  
...  
Keyword(s):  
Liver Injury ◽  
Drug Induced ◽  
Over The Counter ◽  
Drug Induced Liver Injury ◽  
Counter Medication

scholarly journals Paradoxical Patterns of Sinusoidal Obstruction Syndrome-Like Liver Injury in Aged Female CD-1 Mice Triggered by Cannabidiol-Rich Cannabis Extract and Acetaminophen Co-Administration

Molecules ◽  
2019 ◽  
Vol 24 (12) ◽  
pp. 2256 ◽  
Author(s):  
Laura E. Ewing ◽  
Mitchell R. McGill ◽  
Eric U. Yee ◽  
Charles M. Quick ◽  
Charles M. Skinner ◽  
...  
Keyword(s):  
Liver Injury ◽  
Clinical Biochemistry ◽  
Sesame Oil ◽  
Glutathione Depletion ◽  
Sinusoidal Obstruction Syndrome ◽  
Drug Induced ◽  
Over The Counter ◽  
Drug Induced Liver Injury ◽  
Cannabis Extract ◽  
And Oxidative Stress

The goal of this study was to investigate the potential for a cannabidiol-rich cannabis extract (CRCE) to interact with the most common over-the-counter drug and the major known cause of drug-induced liver injury–acetaminophen (APAP)–in aged female CD-1 mice. Gavaging mice with 116 mg/kg of cannabidiol (CBD) [mouse equivalent dose (MED) of 10 mg/kg of CBD] in CRCE delivered with sesame oil for three consecutive days followed by intraperitoneally (i.p.) acetaminophen (APAP) administration (400 mg/kg) on day 4 resulted in overt toxicity with 37.5% mortality. No mortality was observed in mice treated with 290 mg/kg of CBD+APAP (MED of 25 mg/kg of CBD) or APAP alone. Following CRCE/APAP co-administration, microscopic examination revealed a sinusoidal obstruction syndrome-like liver injury–the severity of which correlated with the degree of alterations in physiological and clinical biochemistry end points. Mechanistically, glutathione depletion and oxidative stress were observed between the APAP-only and co-administration groups, but co-administration resulted in much greater activation of c-Jun N-terminal kinase (JNK). Strikingly, these effects were not observed in mice gavaged with 290 mg/kg CBD in CRCE followed by APAP administration. These findings highlight the potential for CBD/drug interactions, and reveal an interesting paradoxical effect of CBD/APAP-induced hepatotoxicity.

Leberschaden unter oraler Antikoagulation, Statin- und ACE-Hemmertherapie

Praxis ◽  
2010 ◽  
Vol 99 (21) ◽  
pp. 1259-1265 ◽  
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.

Drug-induced liver injury network (DILIN)

Hepatology ◽  
2004 ◽  
Vol 40 (4) ◽  
pp. 773-773 ◽  
Author(s):  
Jay H. Hoofnagle
Keyword(s):  
Liver Injury ◽  
Drug Induced ◽  
Drug Induced Liver Injury
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