scholarly journals Beneficial effects of α-lipoic acid in diabetes- and drug- induced liver injury

2018 ◽  
Vol 70 (4) ◽  
pp. 621-628
Author(s):  
Aleksandra Uskokovic ◽  
Svetlana Dinic ◽  
Nevena Grdovic ◽  
Jelena Arambasic-Jovanovic ◽  
Melita Vidakovic ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Damage ◽  
Lipoic Acid ◽  
Drug Toxicity ◽  
Tissue Injury ◽  
Redox Homeostasis ◽  
Drug Induced ◽  
Drug Induced Liver Injury ◽  
Beneficial Effects ◽  
Slowing Down

This review summarizes the effects of ?-lipoic acid (LA) on liver damage and complications in diabetes and drug toxicity. LA is a naturally occurring dithiol compound that plays an essential role in mitochondrial metabolism in its protein-bound form. In contrast, free LA in supplements has diverse biological actions, and its antioxidant effect is its most studied and important activity. Due to its strong antioxidant potential, LA could have a promising role in the treatment of pathologies resulting from an imbalance in redox homeostasis. This includes diabetes, which produces deleterious effects on many organs, including the liver. In diabetes specifically, LA prevents ?-cell destruction, enhances glucose uptake, and its antioxidant effects may be particularly useful in slowing down the development of diabetic complications. Diabetesrelated liver damage is a serious complication in which oxidative stress is the main contributor to tissue injury. Oxidative stress is regarded as one of the main pathological mechanisms underlying liver pathologies provoked by other insults, such as drug toxicity, where LA could also be a useful agent in therapeutic intervention. However, before wider application of LA in a clinical setting, experimental and clinical research needs to be extended.

scholarly journals N-Acetyl Cysteine as an Adjunct in the Treatment of Tuberculosis

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Dawit A. Ejigu ◽  
Solomon M. Abay
Keyword(s):  
Oxidative Stress ◽  
Hearing Loss ◽  
Multidrug Resistant ◽  
Drug Induced ◽  
Drug Induced Liver Injury ◽  
Beneficial Effects ◽  
Tb Treatment ◽  
Mdr Tb ◽  
Acetyl Cysteine ◽  
Karnofsky Performance Index

Oxidative stress is a common feature of tuberculosis (TB), and persons with reduced antioxidants are at more risk of TB. TB patients with relatively severe oxidative stress had also more advanced disease as measured by the Karnofsky performance index. Since adverse effects from anti-TB drugs are also mediated by free radicals, TB patients are prone to side effects, such as hearing loss. In previous articles, researchers appealed for clinical trials aiming at evaluating N-acetyl cysteine (NAC) in attenuating the dreaded hearing loss during multidrug-resistant TB (MDR-TB) treatment. However, before embarking on such trials, considerations of NAC’s overall impact on TB treatment are crucial. Unfortunately, such a comprehensive report on NAC is missing in the literature and this manuscript reviews the broader effect of NAC on TB treatment. This paper discusses NAC’s effect on mycobacterial clearance, hearing loss, drug-induced liver injury, and its interaction with anti-TB drugs. Based on the evidence accrued to date, NAC appears to have various beneficial effects on TB treatment. However, despite the favorable interaction between NAC and first-line anti-TB drugs, the interaction between the antioxidant and some of the second-line anti-TB drugs needs further investigations.

scholarly journals Research on the Species Difference of the Hepatotoxicity of Medicine Based on Transcriptome

2021 ◽  
Vol 12 ◽  
Author(s):  
Ziying Xu ◽  
Qianjun Kang ◽  
Zihui Yu ◽  
Lichun Tian ◽  
Jingxuan Zhang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Animal Models ◽  
Liver Injury ◽  
Drug Toxicity ◽  
Species Difference ◽  
Sprague Dawley ◽  
Drug Induced ◽  
Drug Induced Liver Injury ◽  
Rats And Mice

In recent years, several drugs have been withdrawn from use by regulatory bodies owing to hepatotoxicity; therefore, studies on drug-induced liver injury (DILI) are being actively pursued. Most studies evaluating DILI use rats or mice as animal models to determine drug toxicity; however, the toxicity of a drug can vary between rats or mice. These inconsistencies in in vivo studies among different animal models affect the extrapolation of experimental results to humans. Thus, it is particularly important to choose the most suitable animal model to determine drug hepatotoxicity owing to the genomic differences between rats and mice resulting from evolution. In this study, genome-wide transcriptome analysis was used to explore hepatotoxicity caused by differences in species. Our findings provide the preclinical basis to further study the mechanisms of drug hepatotoxicity and aid in the selection of animal models to determine drug safety. We used murine models (Sprague-Dawley and Wistar rats, ICR and Kunming mice) in this study and by using transcriptome sequencing with the differentially expressed genes in rat and mouse livers as the entry point, we explored the mechanism of oxidative stress and the difference in gene expression in the lipid-metabolism pathway between rats and mice. The clinically established hepatotoxic drugs, fructus psoraleae and acetaminophen were used to validate our study. Using pathological studies, we confirmed that oxidative stress in mice was more serious than that in rats, and that Kunming mice were more suited for the study of oxidative stress-related DILI. The validity of our findings was further verified based on gene expression. Thus, our study could serve as a valuable reference for the evaluation of potential preclinical hepatotoxicity. Moreover, it could be used in the prediction and early diagnosis of drug-induced liver injury caused by traditional Chinese medicine or synthetic drugs, thereby providing a new avenue for drug-toxicity studies.

scholarly journals Isoniazid and Rifampicin Produce Hepatic Fibrosis through an Oxidative Stress-Dependent Mechanism

2020 ◽  
Vol 2020 ◽  
pp. 1-12 ◽  
Author(s):  
Ayan Biswas ◽  
Suman Santra ◽  
Debasree Bishnu ◽  
Gopal Krishna Dhali ◽  
Abhijit Chowdhury ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Injury ◽  
Hepatic Fibrosis ◽  
Stellate Cell ◽  
Progressive Increase ◽  
Drug Induced ◽  
Drug Induced Liver Injury ◽  
Stress Dependent ◽  
Liver Collagen

Background & Aims. Chronic hepatitis (CH) has emerged as a distinct outcome of drug-induced liver injury (DILI). Combination therapy of Isoniazid (INH) and Rifampicin (RMP) which is widely used for prolonged periods can cause acute hepatotoxicity and has been also incriminated in chronic DILI. We sought evidence of the production of hepatic fibrosis on long-term INH-RMP treatment through experiments in BALB/c mice exposed to INH-RMP. Methods. A combined dose of INH (50 mg) and RMP (100 mg) per kg body weight per day was administered to mice by oral gavage, 6 days a week, for 4 to 24 weeks for the assessment of liver injury, oxidative stress, and development of hepatic fibrosis, including demonstration of changes in key fibrogenesis linked pathways and mediators. Results. Progressive increase in markers of hepatic stellate cell (HSC) activation associated with changes in matrix turnover was observed between 12 and 24 weeks of INH-RMP treatment along with the elevation of liver collagen content and significant periportal fibrosis. These were associated with concurrent apoptosis of the hepatocytes, increase in hepatic cytochrome P450 2E1 (CYP2E1), NADPH oxidase (NOX) activity, and development of hepatic oxidative stress. Conclusions. INH-RMP can activate HSC through generation of NOX-mediated oxidative stress, leading to the development of liver fibrosis.

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....

Beneficial effects of dl-α-lipoic acid on cyclophosphamide-induced oxidative stress in mitochondrial fractions of rat testis

2005 ◽  
Vol 152 (1) ◽  
pp. 59-66 ◽  
Author(s):  
Elangovan Selvakumar ◽  
Chidambaram Prahalathan ◽  
Yenjerla Mythili ◽  
Palaninathan Varalakshmi
Keyword(s):  
Oxidative Stress ◽  
Lipoic Acid ◽  
Rat Testis ◽  
Beneficial Effects ◽  
Mitochondrial Fractions

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.

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