[On the inhibitory effect of chloramphenicol on mitochondrial protein synthesis as a possible cause of its selective toxic side effects (author's transl)]

Abstract

The inhibition of protein synthesis by tetracycline and chloramphenicol in mitochondria isolated from rat liver or rabbit bone marrow was investigated in vitro. It could be demonstrated that there is but little difference between the inhibitory effect of both substances in regard to mitochondria protein synthesis. Therefore, a selective interference of chloramphenicol with bone marrow mitochondria cannot be concluded. In in vitro tests the concentrations required for inhibiting the mitochondria protein synthesis are comparable to those found in blood levels measured under usual therapeutic conditions. It can be assumed that in the living organism the mitochondria are protected against tetracycline or chloramphenicol interference. This hypothesis is supported by the fact that due to the increase in the substrate concentration (phenylalanine), the expected inhibition of mitochondrial protein synthesis does not occur. There may be an inhibition of influx of the antibiotic by competition with substrate for transport through mitochondrial membrane. The reason for myelotoxicity of chloramphenicol is not an increased sensitivity of mitochondrial ribosomes located in the bone marrow to chloramphenicol. But the existence of special conditions for chloramphenicol influx into mitochondria of bone marrow must be concluded.