Effect of antibiotics on respiration in human cells

Abstract

Chloramphenicol (CAP), chloramphenicol succinate (CAP-S), tetracycline (TET), and erythromycin (EM) inhibited synthesis of a mitochondrial enzyme, cytochrome oxidase, in cultured human fibroblasts; the 50% inhibitory concentrations were 7.5, 13, 18, and 350 µM respectively, or 2.4, 4.1, 8, and 250 µg/ml. In fibroblasts grown in CAP-S, cytochrome oxidase declined exponentially with a half- life of approximately 2.0 days. Oxygen uptake, on the other hand, was unchanged for the first 24-48 hr of exposure to CAP-S, and then declined, but at a much slower rate than did cytochrome oxidase; after 7 days, cytochrome oxidase activity was 6% of the control value, whereas oxygen uptake was 50% of control. From the kinetic data we conclude that cytochrome oxidase is not normally rate-limiting in cellular respiration, but that, after a period of exposure to CAP-S, an enzyme whose synthesis is inhibited by CAP-S becomes rate-limiting. This enzyme is not cytochrome oxidase, but more likely another component of the respiratory chain. Both CAP and TET inhibited cytochrome oxidase accumulation in non-growing as well as in growing fibroblasts, with enzyme levels declining to 50% of control values in 48 hr; after that time, a new, lower steady state level of enzyme was attained. Oxygen uptake was not inhibited in fibroblasts by short (4-hr) exposure to CAP, CAP-S or TET in concentrations up to 1 mM. © 1972 International Pediatric Research Foundation, Inc.