An in vitro model for assessing muscle irritation of antibiotics using rat primary cultured skeletal muscle fibers.
This study examined the possibility of using rat primary cultured skeletal muscle fiber to estimate the muscle irritation of antibiotics. The cells were exposed to cefaloridine (CER), cefazolin sodium (CEZ), flomoxef sodium (FMOX), cefamandole sodium (CMD), latamoxef sodium (LMOX), or cefalotin sodium (CET) at concentrations of 0 (control), 31.25, 62.5, 125, and 250 mg/ml in culture medium for 1 hr on Day 11 of culture. Cellular creatine kinase (CK) activity was measured as an indication of cell injury. The concentration of the antibiotic, at which CK activity decreased to 50% of the control (depletion concentration 50%, DC50), was utilized as an index of cytotoxicity. DC50s of CER, CEZ, FMOX, CMD, LMOX, and CET were estimated to be 406.7, 311.1, 211.6, 132.7, 114.2, and 56.5 mg/ml, respectively. There was a good correlation between DC50 obtained in the present in vitro test and the irritation volume in the in vivo test. These results suggest that the in vitro system using rat primary cultured skeletal muscle fibers is a useful alternative model for in vivo rabbit study to evaluate muscle irritation.
Kato
I
I
Kanzakigawa Laboratory, Shionogi Research Laboratories, Shionogi & Co., Ltd., Osaka, Japan.
Harihara
A
A
Mizushima
Y
Y
D000818:Animals; D000900:Anti-Bacterial Agents / Q000633:toxicity*; D003402:Creatine Kinase / Q000032:analysis; D046508:Culture Techniques; D005260:Female; D007527:Isoenzymes; D008297:Male; D008954:Models, Biological; D009132:Muscles / Q000187:drug effects* / Q000473:pathology; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley
D000900:Anti-Bacterial Agents; D007527:Isoenzymes; D003402:Creatine Kinase