The State of the Neuronal-Astrocytic Apparatus of the Hippocampus on the Background of Long-Term Administration of Isoniazid and Rifampicin under Conditions of Correction of the Gut Microflora

The purpose of the study was to determine the morphometric and ultrastructural features of neurons and glial cells, as well as the levels of glial fibrillar acid protein in the hippocampus of rats under long-term administration of isoniazid and rifampicin during experimental therapy with a combination of pro/prebiotics. Materials and methods. The studies were conducted on three groups of white Wistar male rats with drug-induced hepatitis, reproduced by intragastric administration of isoniazid and rifampicin for 28 days. In the last 14 days of the intragastric experiment, rats of the research group were administered probiotic and prebiotic. The content of cytosolic glial fibrillar acid protein in the hippocampus was determined by competitive enzyme-linked immunosorbent assay. Semi-thin sections of CA1 sections of the rat hippocampus were analyzed using the Image J. analysis program. The ultrastructural characteristics were studied using a PEM-100-01 transmission electron microscope (Selmi, Ukraine). Results and discussion. Long-term administration of isoniazid and rifampicin was associated with changes in the content of the cytosolic fraction of glial fibrillar acid protein obtained from the hippocampus. These changes were characterized by a tendency to increase the level of this protein by 17.8% (p=0.2) compared with intact animals. In contrast to the group of animals reproduced in the experiment drug-induced liver injury, in the experimental group, the level of glial fibrillar acid protein was significantly lower by 25.0% compared to the drug-induced liver injury group (p <0.05). Morphological analysis revealed a decrease in neuronal density in rats with drug-induced liver injury compared with intact control. At the same time, the specific number of degeneratively altered neurons in comparison with intact control in the group of drug-induced liver injury animals increased by 8.57 times. The number of degeneratively altered neurons in the group receiving yogurt / lactulose was 55.87 ± 4.23%, which was significantly higher than intact control rats, but was 19.4% (p <0.05) lower levels in rats with MIUP. Electron microscopic examination of rat hippocampal neuroglia was based on the study of changes in the astrocytic and oligodendroglial components. Changes in rat hippocampal neuroglia under experimental conditions were mainly related to the astrocytic link. Astrocytes were characterized by significantly lower cytoplasmic edema and adaptive-compensatory changes in the cell. Conclusion. Course administration of pro/prebiotics reduces the severity of manifestations of neurodegeneration, improves the state of astroglia in the hippocampus, and reduces the cytoplasmic levels of glial acidic fibrillar protein in animals with drug-induced liver injury

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Faculty Opinions recommendation of Outcome of acute idiosyncratic drug-induced liver injury: Long-term follow-up in a hepatotoxicity registry.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1071145.524146 ◽

2007 ◽

Author(s):

Stefano Bellentani

Keyword(s):

Liver Injury ◽

Drug Induced ◽

Drug Induced Liver Injury ◽

Long Term Follow Up

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

International Journal of Hepatology ◽

10.1155/2020/6987295 ◽

2020 ◽

Vol 2020 ◽

pp. 1-12 ◽

Cited By ~ 1

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.

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Long-term sequelae of Drug-induced liver injury

Journal of Hepatology ◽

10.1016/j.jhep.2021.10.011 ◽

2021 ◽

Author(s):

Einar S. Björnsson ◽

Raul J. Andrade

Keyword(s):

Liver Injury ◽

Drug Induced ◽

Drug Induced Liver Injury

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Drug-Induced Autoimmune Hepatitis following Treatment with Zoledronic Acid

Case Reports in Gastroenterology ◽

10.1159/000479314 ◽

2017 ◽

Vol 11 (2) ◽

pp. 440-445 ◽

Cited By ~ 4

Author(s):

Jenny Sarah Schneider ◽

Matteo Montani ◽

Felix Stickel

Keyword(s):

Liver Disease ◽

Zoledronic Acid ◽

Side Effects ◽

Liver Injury ◽

Drug Reactions ◽

Drug Induced ◽

Drug Induced Liver Injury ◽

First Case ◽

Alternative Drugs

Adverse drug reactions are among the most frequent side effects of synthetic and complementary alternative drugs and represent the premier causes of license revocations and acute liver failure. Drug-induced liver injury can resemble literally any other genuine liver disease and usually responds well to drug dechallenge. However, in some cases autoimmune-like hepatitis can evolve, requiring short- and sometimes long-term immunosuppression. Here, we present the hitherto first case of autoimmune-like hepatitis following treatment with zoledronic acid.

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A Turn-on Probe for Detecting Antituberculotic Drug-induced Liver Injury in Mice via NIR-II Fluorescence/Optoacoustic Imaging

Chemical Communications ◽

10.1039/d1cc02845f ◽

2021 ◽

Author(s):

Longqi Chen ◽

Junjie Chen ◽

Yichang Fang ◽

Fang Zeng ◽

Shuizhu Wu

Keyword(s):

Infectious Disease ◽

Liver Injury ◽

Causes Of Death ◽

Standard Treatment ◽

Drug Induced ◽

Optoacoustic Imaging ◽

Drug Induced Liver Injury ◽

Turn On

Standard treatment for tuberculosis (TB), an infectious disease and one of the top ten causes of death worldwide, usually lasts for a long term. And the antituberculotic-drug-induced liver injury has...

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