Chloramphenicol-Related Changes in Mitochondrial Ultrastructure

Abstract

An electron-microscopic examination of bone marrow mitochondria derived from 10 patients before and after chloramphenicol (CAP) therapy has shown that CAP induces an ultrastructural modification resulting in an increase in the density of the mitochondrial matrix. These changes resemble the condensed mitochondrial configurations which have previously been interpreted in terms of electron transfer and oxidative phosphorylation. However, in the concentrations employed in this study, CAP has no effect on mitochondrial respiration or on oxidative phosphorylation, but is a potent inhibitor of mitochondrial protein synthesis. Evidence relating this effect of the drug to its myelotoxicity has been supported by a comparative study demonstrating lack of effect of a drug such as tetracycline which is not known to be myelotoxic, and the excellent correlation between the extensiveness of mitochondrial changes in the marrow and the serum level of free CAP. The results were confirmed in a parallel study on insect flight muscle mitochondria, in which the metabolic state under which the drug is administered can be con trolled and where the regular disposition of the mitochondrial cristae provides an ideal model for the study of configurational changes.