Comparison of dantrolene sodium with erythromycin estolate using primary cultures of rat hepatocytes.
Using primary cultures of parenchymal hepatocytes as a model system, the cytotoxic potential of dantrolene sodium (DS) was compared with that of erythromycin estolate (EE)--a known hepatotoxin. Parallel morphological and functional comparisons were made, following 4-, 8-, or 24-h exposures of hepatocyte cultures, using phase contrast microscopy and lactate dehydrogenase (LDH) leakage, respectively. Four-hour exposures of cultures to rather low concentrations of EE (i.e. 50 microM) resulted in cellular necrosis and significantly elevated LDH release. As the concentration of this hepatotoxin was increased, the changes were more pronounced. However, even 4- or 8-h exposures of cultures to a maximum of 100 microM DS did not affect LDH leakage or morphological integrity, although marginally detectable morphological changes did not occur at the highest concentration after 24-h. The value of using primary parenchymal hepatocyte cultures as a model system for the assessment of xenobiotic-induced hepatotoxicity was confirmed.
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism / Q000473:pathology; D003620:Dantrolene / Q000633:toxicity*; D004917:Erythromycin / Q000031:analogs & derivatives*; D004918:Erythromycin Estolate / Q000633:toxicity*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D051381:Rats; D011919:Rats, Inbred Strains
D004917:Erythromycin; D007770:L-Lactate Dehydrogenase; D003620:Dantrolene; D004918:Erythromycin Estolate