Journal
CURRENT ISSUES IN MOLECULAR BIOLOGY
Volume 44, Issue 10, Pages 4639-4657Publisher
MDPI
DOI: 10.3390/cimb44100317
Keywords
antibiotics; drug-induced liver injury; hepatotoxicity
Categories
Funding
- University of Rostock
- European Regional Development Fund (EFRE)
- European Social Fund (ESF) [AU 09 046:ESF/IV-BM-B35-0005/12]
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Antibiotics are crucial in fighting bacterial infections, but some of them can cause hepatotoxicity.
(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, 5x Cmax, and 10x 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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