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Influence of Antibiotics on Functionality and Viability of Liver Cells In Vitro

(1) Antibiotics are an important weapon in the fight against serious bacterial infections and are considered a common cause of drug-induced liver injury (DILI). The hepatotoxicity of many drugs, including antibiotics, is poorly analyzed in human in vitro models. (2) A standardized assay with a human...

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Autores principales: Doß, Sandra, Blessing, Corinne, Haller, Katharina, Richter, Georg, Sauer, Martin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9600611/
https://www.ncbi.nlm.nih.gov/pubmed/36286032
http://dx.doi.org/10.3390/cimb44100317
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author Doß, Sandra
Blessing, Corinne
Haller, Katharina
Richter, Georg
Sauer, Martin
author_facet Doß, Sandra
Blessing, Corinne
Haller, Katharina
Richter, Georg
Sauer, Martin
author_sort Doß, Sandra
collection PubMed
description (1) Antibiotics are an important weapon in the fight against serious bacterial infections and are considered a common cause of drug-induced liver injury (DILI). The hepatotoxicity of many drugs, including antibiotics, is poorly analyzed in human in vitro models. (2) A standardized assay with a human hepatoma cell line was used to test the hepatotoxicity of various concentrations (Cmax, 5× Cmax, and 10× Cmax) of antibiotics. In an ICU, the most frequently prescribed antibiotics, ampicillin, cefepime, cefuroxime, levofloxacin, linezolid, meropenem, rifampicin, tigecycline, and vancomycin, were incubated with HepG2/C3A cells for 6 days. Cell viability (XTT assay, LDH release, and vitality), albumin synthesis, and cytochrome 1A2 activity were determined in cells. (3) In vitro, vancomycin, rifampicin, and tigecycline showed moderate hepatotoxic potential. The antibiotics ampicillin, cefepime, cefuroxime, levofloxacin, linezolid, and meropenem were associated with mild hepatotoxic reactions in test cells incubated with the testes Cmax concentration. Rifampicin and cefuroxime showed significantly negative effects on the viability of test cells. (4) Further in vitro studies and global pharmacovigilance reports should be conducted to reveal underlying mechanism of the hepatotoxic action of vancomycin, rifampicin, tigecycline, and cefuroxime, as well as the clinical relevance of these findings.
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spelling pubmed-96006112022-10-27 Influence of Antibiotics on Functionality and Viability of Liver Cells In Vitro Doß, Sandra Blessing, Corinne Haller, Katharina Richter, Georg Sauer, Martin Curr Issues Mol Biol Article (1) Antibiotics are an important weapon in the fight against serious bacterial infections and are considered a common cause of drug-induced liver injury (DILI). The hepatotoxicity of many drugs, including antibiotics, is poorly analyzed in human in vitro models. (2) A standardized assay with a human hepatoma cell line was used to test the hepatotoxicity of various concentrations (Cmax, 5× Cmax, and 10× Cmax) of antibiotics. In an ICU, the most frequently prescribed antibiotics, ampicillin, cefepime, cefuroxime, levofloxacin, linezolid, meropenem, rifampicin, tigecycline, and vancomycin, were incubated with HepG2/C3A cells for 6 days. Cell viability (XTT assay, LDH release, and vitality), albumin synthesis, and cytochrome 1A2 activity were determined in cells. (3) In vitro, vancomycin, rifampicin, and tigecycline showed moderate hepatotoxic potential. The antibiotics ampicillin, cefepime, cefuroxime, levofloxacin, linezolid, and meropenem were associated with mild hepatotoxic reactions in test cells incubated with the testes Cmax concentration. Rifampicin and cefuroxime showed significantly negative effects on the viability of test cells. (4) Further in vitro studies and global pharmacovigilance reports should be conducted to reveal underlying mechanism of the hepatotoxic action of vancomycin, rifampicin, tigecycline, and cefuroxime, as well as the clinical relevance of these findings. MDPI 2022-10-03 /pmc/articles/PMC9600611/ /pubmed/36286032 http://dx.doi.org/10.3390/cimb44100317 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Doß, Sandra
Blessing, Corinne
Haller, Katharina
Richter, Georg
Sauer, Martin
Influence of Antibiotics on Functionality and Viability of Liver Cells In Vitro
title Influence of Antibiotics on Functionality and Viability of Liver Cells In Vitro
title_full Influence of Antibiotics on Functionality and Viability of Liver Cells In Vitro
title_fullStr Influence of Antibiotics on Functionality and Viability of Liver Cells In Vitro
title_full_unstemmed Influence of Antibiotics on Functionality and Viability of Liver Cells In Vitro
title_short Influence of Antibiotics on Functionality and Viability of Liver Cells In Vitro
title_sort influence of antibiotics on functionality and viability of liver cells in vitro
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9600611/
https://www.ncbi.nlm.nih.gov/pubmed/36286032
http://dx.doi.org/10.3390/cimb44100317
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