Cantin A, Woods D E
Unité de Recherche Pulmonaire, Centre Hospitalier Universitaire de Sherbrooke, Quebec, Canada.
J Clin Invest. 1993 Jan;91(1):38-45. doi: 10.1172/JCI116196.
Myeloperoxidase, in the presence of noncytotoxic concentrations of H2O2, was used to induce cytotoxicity to the lung epithelial cell line, AKD. When the cationic aminoglycosides, tobramycin and gentamicin were added to the cells in the presence of myeloperoxidase and H2O2, cytotoxicity was completely inhibited. In addition, tobramycin prevented cytotoxicity induced by cystic fibrosis sputum and H2O2. Protection against myeloperoxidase and H2O2 was also observed with the thioether-containing antibiotics, ticarcillin and ceftazidime, but at higher concentrations than with the aminoglycosides. Analysis of spectral properties, dimethylsulfoxide-mediated reduction, and ethyl acetate/NaCl partitioning, demonstrated that aminoglycosides converted HOCl to hydrophilic noncytotoxic chloramines, but were unable to prevent the oxidation of sulfhydryls and methionine by HOCl. In contrast, ticarcillin and ceftazidime were highly effective inhibitors of HOCl-mediated sulfhydryl and methionine oxidation. These results suggest that aminoglycosides protect lung epithelial cells against myeloperoxidase-dependent oxidant injury by binding to anionic cell surfaces and converting HOCl to hydrophilic noncytotoxic chloramines, whereas penicillins and cephalosporins are potent HOCl scavengers capable of protecting critical extracellular molecules against oxidation.
在非细胞毒性浓度的过氧化氢存在下，髓过氧化物酶被用于诱导对肺上皮细胞系AKD的细胞毒性。当在髓过氧化物酶和过氧化氢存在的情况下，将阳离子氨基糖苷类药物妥布霉素和庆大霉素添加到细胞中时，细胞毒性被完全抑制。此外，妥布霉素可预防由囊性纤维化痰液和过氧化氢诱导的细胞毒性。含硫醚的抗生素替卡西林和头孢他啶也观察到对髓过氧化物酶和过氧化氢的保护作用，但所需浓度高于氨基糖苷类药物。光谱性质分析、二甲亚砜介导的还原以及乙酸乙酯/氯化钠分配表明，氨基糖苷类药物将次氯酸转化为亲水性非细胞毒性氯胺，但无法防止次氯酸对巯基和蛋氨酸的氧化。相比之下，替卡西林和头孢他啶是次氯酸介导的巯基和蛋氨酸氧化的高效抑制剂。这些结果表明，氨基糖苷类药物通过与阴离子细胞表面结合并将次氯酸转化为亲水性非细胞毒性氯胺，从而保护肺上皮细胞免受髓过氧化物酶依赖性氧化损伤，而青霉素和头孢菌素是强大的次氯酸清除剂，能够保护关键的细胞外分子免受氧化。
