scholarly journals Weaning Mice and Adult Mice Exhibit Differential Carbon Tetrachloride-Induced Acute Hepatotoxicity

Antioxidants ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 201 ◽  
Author(s):  
Tae Bin Jeong ◽  
Doyoung Kwon ◽  
Seung Won Son ◽  
Sou Hyun Kim ◽  
Yun-Hee Lee ◽  
...  
Keyword(s):  
Liver Injury ◽  
Liver Damage ◽  
Drug Induced ◽  
Glutamate Cysteine Ligase ◽  
Stress Indicators ◽  
Drug Induced Liver Injury ◽  
Adult Mice ◽  
Cellular Events ◽  
Cyp 2E1 ◽  
Old Adult

Age is a risk factor for drug-induced liver injury (DILI). However, there is a limited understanding of pediatric DILI. Here, 2-week-old weaning and 8-week-old adult male ICR mice were intraperitoneally injected with CCl4 (0.1 mmol/kg equal to 15.4 mg/kg) to comparatively evaluate the time-dependent liver damage and cellular events. CCl4 significantly enhanced the serum alanine aminotransferase/aspartate aminotransferase levels and hepatic centrilobular necrosis in the weaning mice, whereas it induced mild liver injury in the adult mice. CCl4-treated weaning mice exhibited higher hepatic levels of pro-apoptotic proteins (Bax, cleaved caspase-3, -7, and -9), activated MAPKs (p-JNK and p-Erk), and endoplasmic reticulum stress indicators (ATF6 and CHOP) and lower hepatic anti-apoptotic Bcl-2 levels than the adult mice. The weaning mice exhibited enhanced basal hepatic glutathione (GSH) levels due to high glutamate cysteine ligase (GCL) and low anti-cysteine dioxygenase (CDO) enzyme levels. However, CCl4 markedly reduced the hepatic GSH levels only in the weaning mice. Furthermore, higher hepatic levels of oxidative stress-induced malondialdehyde, 4-hydroxynonenal, nitrotyrosine-protein adducts, and oxidized proteins were observed in CCl4-treated weaning mice than in CCl4-treated adult mice. The enhanced levels of hepatic cytochrome P450 (CYP) 2E1 and CYP3A, and decreased hepatic GSH S-transferase (GST)-π and GSH reductase (GR) levels in the weaning mice may contribute to their enhanced susceptibility to liver damage.

scholarly journals BML-257, a small molecule that protects against drug induced liver injury in zebrafish

2022 ◽  
Author(s):  
Urmila Jagtap ◽  
Sandeep Basu ◽  
Lavanya Lokhande ◽  
Nikhil Bharti ◽  
Chetana Sachidanandan
Keyword(s):  
Liver Injury ◽  
Small Molecule ◽  
Liver Damage ◽  
Protective Action ◽  
Damage Model ◽  
Akt Inhibitor ◽  
Drug Induced ◽  
Specific Expression ◽  
Drug Induced Liver Injury ◽  
Chemical Screen

The use of many essential drugs is restricted due to their deleterious effects on the liver. Molecules that can prevent or protect the liver from drug induced liver injury (DILI) would be valuable in such situations. We used hepatocyte-specific expression of bacterial nitroreductase in zebrafish to cause temporally controlled liver damage. This transgenic line was used to run a whole organism based chemical screen in zebrafish larvae. In this screen we identified BML-257, a potent small molecule AKT inhibitor, that protected the liver against metronidazole-induced liver injury. BML-257 also showed potent prophylactic and pro-regenerative activity in this liver damage model. BML-257 also showed remarkable protective action in two independent toxicological models of liver injury caused by acetaminophen and Isoniazid. This suggests that BML-257 may have the potential to protect against multiple kinds of drug induced liver injury.

Drugs and liver damage

2010 ◽  
pp. 2527-2537
Author(s):  
J. Neuberger
Keyword(s):  
Liver Disease ◽  
Liver Injury ◽  
Pulmonary Tuberculosis ◽  
Liver Damage ◽  
Case History ◽  
Genetic Component ◽  
Drug Induced ◽  
Drug Induced Liver Injury ◽  
Almost All

Case History—A 22 yr old man, being treated for pulmonary tuberculosis, now presenting with confusion and jaundice. Drug-induced liver injury (DILI) is relatively uncommon but can very rarely be fatal. Almost all patterns of liver disease can be induced by drugs, and some drugs may be associated with more than one type of reaction. Some cases of DILI have a genetic component. Most cases present with jaundice and/or hepatitis....

scholarly journals Relationship between CYP2E1 Gene Polymorphism and Anti-tuberculosis Drug-induced Liver Injury

2018 ◽  
Vol 1 (4) ◽  
pp. 105
Author(s):  
Donglin Zhu ◽  
Yun Xi ◽  
Jieming Dong ◽  
Fanhua Huang ◽  
Changzhi Xu ◽  
...  
Keyword(s):  
Liver Injury ◽  
Gene Polymorphism ◽  
Liver Damage ◽  
Gene Polymorphisms ◽  
Control Group ◽  
Case Group ◽  
Chinese Han ◽  
Drug Induced ◽  
Drug Induced Liver Injury ◽  
Cyp2e1 Gene

 Objective: To investigate the relationship between cytochrome P450 E1 (CYP2E1) gene polymorphisms and susceptibility to anti-tuberculosis drug-induced liver damage (ATDLI) in tuberculosis patients in the Chinese Han nationality. Methods: A retrospective analysis was performed on 360 patients with tuberculosis who had liver damage after tuberculosis treatment (case group) and 360 patients with tuberculosis who did not develop liver injury after treatment (control group). MassARRAY were used to detect CYP2E1 gene polymorphisms. Results: In a total of 8 tagged SNP loci selected, the rs8192773 locus failed to pass the test, and therefore, it is not included in subsequent analysis. At the remaining seven SNP sites, the difference in alleles was not statistically significant between the case group and the control group, suggesting that these sites may not be related to liver damage caused by anti-tuberculosis drugs. Three monomer domains were found in the seven tags SNP loci mentioned above. However, it was found that these haplotypes are not closely related to anti-tuberculosis drug-induced liver damage. Conclusion: The CYP2E1 gene polymorphism in the Chinese Han nationality is not related to the occurrence of anti-tuberculosis drug-induced liver injury.

Current conservative treatment of uterine fibroids. Ulipristal acetate and liver damage: contrived tragedy?

GYNECOLOGY ◽  
2018 ◽  
Vol 20 (6) ◽  
pp. 4-7
Author(s):  
A L Tikhomirov
Keyword(s):  
Risk Assessment ◽  
Liver Injury ◽  
Liver Damage ◽  
Uterine Fibroids ◽  
Tumor Formation ◽  
Drug Induced ◽  
Ulipristal Acetate ◽  
Drug Induced Liver Injury ◽  
Pharmacovigilance Risk Assessment Committee ◽  
Assessment Committee

Uterine fibroids are the most common pelvic tumor formation in women and the most common indication for hysterectomy. The effectiveness of long-term intermittent use of ulipristal acetate (UA) in patients with uterine myoma has been proven earlier. In May 2018, the ability of UA to cause a drug-induced liver injury (drug-induced liver injury, DILI) was disproved, and the European Commission approved a positive decision. According to the conclusion Expertise of the Pharmacovigilance Risk Assessment Committee (Pharmacovigilance Risk Assessment Committee - PRAC) the benefit/risk ratio remains favorable. Published recommendations are aimed at reducing the risk of liver damage. UA remains the 1st line of treatment for most myomas.

scholarly journals Optimizing diagnostic approach to drug-induced liver injury

2018 ◽  
Vol 12 (3) ◽  
pp. 180-189 ◽  
Author(s):  
Maria Giovanna Minissale ◽  
Maurizio Soresi ◽  
Massimo Galia ◽  
Francesco Agnello ◽  
Lydia Giannitrapani ◽  
...  
Keyword(s):  
Liver Injury ◽  
Liver Damage ◽  
Transient Elastography ◽  
Liver Stiffness ◽  
Abdominal Ultrasound ◽  
Liver Function Tests ◽  
Accurate Method ◽  
Focal Lesions ◽  
Drug Induced ◽  
Drug Induced Liver Injury

Drug-induced liver injury (DILI) is often a trial even to expert clinicians, because sometimes diagnosis is not easy to be made. Guidelines of the American College of Gastroenterology (ACG) yielded in 2014, help to better understand the problem. The diagnosis of DILI is made through a detailed evaluation of clinical, serological, radiological and histological aspects. Biochemical data include liver function tests that allow to assess the pattern of damage, such as hepatocellular, cholestatic and mixed liver injury; serological data include testing for major and possibly minor hepatotropic viruses, non-organ specific autoantibodies. Clinical scenario might include jaundice, nausea, vomiting and extra-hepatic manifestations such as fever, pruritus, rash and eosinophilia. Investigation of the potential culprit drugs should involve firstly the temporal relationship between intake of the medication and onset of symptoms, thus the improvement after drug withdrawal. Overall, to complete the diagnostic evaluation, an abdominal ultrasound can be performed, as well as measurement of liver stiffness by transient elastography, and finally liver biopsy, which still represents the most accurate method to definitely assess liver damage. Sometimes, in such cases, computed tomography scan and magnetic resonance could help in the diagnosis of cases presenting with focal lesions of the liver, with cholestatic-like disease or vascular alterations, such as veno-occlusive disease. DILI diagnostic criteria help clinicians thinking of liver injury induced by drug, excluding other causes of liver disease. According to severity of liver damage and type of drug, it is possible to carefully predict the patient’s outcome.

669 Chronic liver damage after an episode of idiosyncratic drug induced liver injury (DILI)

2006 ◽  
Vol 44 ◽  
pp. S247
Author(s):  
R.J. Andrade ◽  
M.I. Lucena ◽  
K. Pachkoria ◽  
Y. Borraz ◽  
N. Kaplowitz ◽  
...  
Keyword(s):  
Liver Injury ◽  
Liver Damage ◽  
Chronic Liver ◽  
Drug Induced ◽  
Chronic Liver Damage ◽  
Drug Induced Liver Injury

scholarly journals Drug Induced Hepatotoxicity – An Ongoing Challenge

2020 ◽  
Vol 10 (3) ◽  
pp. 244-248
Author(s):  
Mehr Fatima ◽  
Syed Zaidi
Keyword(s):  
Liver Injury ◽  
Liver Failure ◽  
Liver Damage ◽  
Obese People ◽  
Drug Induced ◽  
Pharmacological Agents ◽  
Drug Induced Liver Injury ◽  
High Incidence ◽  
Inflammatory Drugs

Drug induced liver injury is one of the main factor of liver failure and acute liver damage world wide with high incidence in western countries. Liver injury can be intrinsic (dose dependant) or idiosyncratic (dose independent). However idiosyncratic type is considered to be mainly responsible for drug induced liver damage. Binding of reactive metabolites of drugs to tissue proteins and oxidative stress is the possible cellular mechanism involved in this process. Moreover, some antibiotics, anti-epileptics, nonsteroidal anti-inflammatory drugs etc are more likely to induce liver damage in high risks groups that includes females, elderly and obese people. HLA halotype and variation in protein expression also plays an important role in this context. Various studies are available regarding clinical features, histopathological features, diagnosis and management related to antibiotics and acetaminophen induced liver damage. N acetylcysteine is commonly available antidote for drug induced hepatic damage. Role of other pharmacological agents as an antidote requires further studies. However, liver transplantation should be considered with drug induced lethal liver failure

scholarly journals The Immunological Mechanisms and Immune-Based Biomarkers of Drug-Induced Liver Injury

2021 ◽  
Vol 12 ◽  
Author(s):  
Wenhui Liu ◽  
Xiangchang Zeng ◽  
Yating Liu ◽  
Jinfeng Liu ◽  
Chaopeng Li ◽  
...  
Keyword(s):  
Immune Response ◽  
Liver Injury ◽  
New Drugs ◽  
Drug Induced ◽  
Drug Induced Liver Injury ◽  
Cellular Events ◽  
Immunological Mechanisms ◽  
Close Relationship ◽  
Life Threatening ◽  
Underlying Mechanisms

Drug-induced liver injury (DILI) has become one of the major challenges of drug safety all over the word. So far, about 1,100 commonly used drugs including the medications used regularly, herbal and/or dietary supplements, have been reported to induce liver injury. Moreover, DILI is the main cause of the interruption of new drugs development and drugs withdrawn from the pharmaceutical market. Acute DILI may evolve into chronic DILI or even worse, commonly lead to life-threatening acute liver failure in Western countries. It is generally considered to have a close relationship to genetic factors, environmental risk factors, and host immunity, through the drug itself or its metabolites, leading to a series of cellular events, such as haptenization and immune response activation. Despite many researches on DILI, the specific biomarkers about it are not applicable to clinical diagnosis, which still relies on the exclusion of other causes of liver disease in clinical practice as before. Additionally, circumstantial evidence has suggested that DILI is mediated by the immune system. Here, we review the underlying mechanisms of the immune response to DILI and provide guidance for the future development of biomarkers for the early detection, prediction, and diagnosis of DILI.

Drug-induced liver injury

2011 ◽  
Author(s):  
R. Mark Beattie ◽  
Anil Dhawan ◽  
John W.L. Puntis
Keyword(s):  
Risk Factors ◽  
Liver Injury ◽  
Drug Metabolism ◽  
Clinical Features ◽  
Liver Damage ◽  
Herbal Drugs ◽  
Drug Induced ◽  
Drug Induced Liver Injury ◽  
Alternative Medicines

Epidemiology 374Pathophysiology 374Herbal drugs and alternative medicines 377Risk factors 377Clinical features 378Investigation 379Management 380Drug induced liver injury (DILI) is a variable and complex diagnosis of exclusion, as it can present in different ways. Because of the liver's central role in drug metabolism, most prescribed drugs can cause liver injury. Liver damage can occur through drugs in a predictable, intrinsic dose-related way or in a unpredictable, idiosyncratic dose-unrelated fashion....

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