Chloramphenicol and bone marrow mitochondria.

Abstract

Abstract The mechanism of bone marrow depression from chloramphenicol (CAP) remains unknown. Although CAP is a specific inhibitor of ribosomal protein synthesis in sensitive bacteria, it has little effect on ribosomal protein synthesis in mammalian cells. Recent investigations have established that mitochondria isolated from various mammalian tissues are capable of independent protein synthesis and that this process is sensitive to small concentrations of CAP. Thus interference with mitochondrial function may be a major underlying mechanism in CAP toxicity. To test this hypothesis, a study has been made on the effect of CAP on mitochondria isolated from rabbit and human bone marrow. Chloramphenicol in concentrations within therapeutic range inhibited mitochondrial protein synthesis without affecting mitochondrial respiration or oxidative phosphorylation. Evidence relating this in vitro effect of CAP to its myelotoxicity has been derived from: (1) a comparative study with antibiotics not known to be myelotoxic, and (2) electron microscopic observations on bone marrow cells from patients receiving CAP. The data lend strong support to the hypothesis that inhibition of mitochondrial protein synthesis is the biochemical basis for reversible bone marrow depression from CAP.