Williams P D, Masters B G, Evans L D, Laska D A, Hottendorf G H
Fundam Appl Toxicol. 1987 Jul;9(1):10-7. doi: 10.1016/0272-0590(87)90148-5.
A rat skeletal muscle cell line (L6) was evaluated for its potential to discriminate the muscle-irritating liability of several parenteral antibiotics. The cells were exposed to clinical as well as diluted concentrations of tetracycline, cefoxitin, cephalothin, carbenicillin, erythromycin, ceforanide, cefazolin, and cephaloridine for 1 hr. Control cells were similarly exposed to culture media for 1 hr. The cells were subsequently assayed for their content of the muscle-associated enzyme creatine kinase (CK). Depletion of CK relative to control cultures was utilized as the index of cellular damage. The results of these analyses revealed the following ranking of antibiotic toxicity to L6 muscle cells: tetracycline, erythromycin, cefoxitin greater than cephalothin, carbenicillin greater than ceforanide, cefazolin greater than cephaloridine. The relative order of toxicity of these antibiotics to L6 cells is in good agreement with their reported muscle-irritating liability in man. The correlation between the results obtained in vitro and the irritancy data in vivo suggests that this model may be a useful adjunct to in vivo testing of parenteral antibiotics for muscle-irritation liability.
对一种大鼠骨骼肌细胞系(L6)进行了评估,以确定其区分几种注射用抗生素肌肉刺激性的潜力。将细胞暴露于四环素、头孢西丁、头孢噻吩、羧苄青霉素、红霉素、头孢尼西、头孢唑林和头孢菌素的临床浓度以及稀释浓度下1小时。对照细胞同样暴露于培养基中1小时。随后测定细胞中肌肉相关酶肌酸激酶(CK)的含量。相对于对照培养物,CK的消耗被用作细胞损伤的指标。这些分析结果显示了这些抗生素对L6肌肉细胞的毒性排名如下:四环素、红霉素、头孢西丁大于头孢噻吩、羧苄青霉素大于头孢尼西、头孢唑林大于头孢菌素。这些抗生素对L6细胞的相对毒性顺序与它们在人体中报道的肌肉刺激性非常一致。体外获得的结果与体内刺激性数据之间的相关性表明,该模型可能是注射用抗生素肌肉刺激性体内测试的有用辅助手段。