Erythromycin toxicity in primary cultures of rat hepatocytes.
Cultured rat hepatocytes were used to study the toxicity of erythromycin base (EB), erythromycin estolate (EE) and a new fluorinated derivative, (8S)-8-fluoroerythromycin A (EF). EF was not cytotoxic after 18 h incubation at concentrations up to 8 X 10(-4) M and EE was much more toxic than EB at all concentrations studied. EE toxicity was greater in a serum-free medium and was not increased by induction of cytochrome P-450 with phenobarbitone. In hepatocytes co-cultured with rat-liver epithelial cells EE, but not EF, raised the cytochrome P-450 content and formed stable cytochrome P-450 complexes with about 40% of the haemoprotein. The lack of correlation between cytochrome P-450 content and cytotoxicity suggests that some of the parent erythromycin drugs and not their metabolites are the toxic entities.
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004917:Erythromycin / Q000031:analogs & derivatives / Q000633:toxicity*; D004918:Erythromycin Estolate / Q000633:toxicity; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
C045925:flurithromycin; D004917:Erythromycin; D003577:Cytochrome P-450 Enzyme System; D007770:L-Lactate Dehydrogenase; D004918:Erythromycin Estolate