Cytotoxicity of macrolide antibiotics in a cultured human liver cell line

• Published in: Journal of antimicrobial chemotherapy Vol. 38; no. 3; pp. 465 - 473
• Main Authors: Viluksela, Matti, Vainio, Petri J., Tuominen, Raimo K.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01-09-1996
• Subjects: Anti-Bacterial Agents - pharmacology; Anti-Bacterial Agents - toxicity; Azithromycin - pharmacology; Azithromycin - toxicity; Biological and medical sciences; Cell Line; Clarithromycin - pharmacology; Clarithromycin - toxicity; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical - methods; Drug toxicity and drugs side effects treatment; Epithelial Cells; Epithelium - drug effects; Erythromycin - analogs & derivatives; Erythromycin - pharmacology; Erythromycin - toxicity; Humans; Liver - cytology; Liver - drug effects; Liver - metabolism; Medical sciences; Pharmacology. Drug treatments; Proteins - drug effects; Proteins - metabolism; Roxithromycin - pharmacology; Roxithromycin - toxicity; Tetrazolium Salts - chemistry; Thiazoles - chemistry; Toxicity: digestive system; Human; Cell culture; Antibiotic; Digestive system; Toxicity; Liver; Cytotoxicity; Antibacterial agent; In vitro; Macrolide
• ISSN: 0305-7453; 1460-2091
• DOI: 10.1093/jac/38.3.465

Cytotoxicity of erythromycin base, erythromycin estolate, erythromycin-11,12-cyclic carbonate, roxithromycin, clarithromycin and azithromycin was compared in cultured human non-malignant Chang liver cells using reduction of 3-{4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide and cellular protein concentration as end points of toxicity. Erythromycin estolate was the most toxic macrolide in all tests differing clearly from all the other macrolides studied. Erythromycin-11,12-cyclic carbonate was also more toxic than the other macrolides. Roxithromycin and clarithromycin were the next toxic derivatives, while erythromycin base and azithromycin were least toxic. Thus, cytotoxicity of the new semisynthetic macrolides, roxithromycin, clarithromycin and azithromycin, is not substantially different from that of erythromycin base. In view of the low level of hepatotoxicity of macrolides hitherto reported in humans, the results do not suggest any substantial risk for hepatic disorders related to the use of azithromycin, clarithromycin and roxithromycin.