Mitochondrial lesions in reversible erythropoietic depression due to chloramphenicol.
The mechanism underlying the reversible depression of erythropoiesis by chloramphenicol has been investigated in rabbits in which hemolytic anemia had been induced by phenylhydrazine so that the compensatory erythroid hyperplasia would provide a situation where abnormalities in the bone marrow cells reflected predominantly those of erythroid precursors. Maintenance of chloramphenicol in the serum of these animals at concentrations in the order of 15 mug/ml resulted in erythropoietic depression after several days. The onset of this depression corresponded to the development of a cellular respiratory defect in the erythroid precursors which was associated with an abnormality in the composition of the mitochondrial respiratory pathway. The abnormality took the form of a selective depletion of cytochromes a + a(3) and b which can be explained by an inhibitory effect of the antibiotic on their formation by the mitochondrial protein-synthesizing system. The relationship between the mitochondrial lesion and the depression of proliferative activity was further indicated by the correlation between the restoration of the cytochrome deficit and the recovery of erythropoiesis after chloramphenicol administration was ceased. The features of the reversible depression of erythropoiesis corresponded closely to those in man, so that a specific action of chloramphenicol on mitochondrial formation provides a reasonable explanation for this important manifestation of chloramphenicol toxicity.
D000743:Anemia, Hemolytic / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001345:Autoradiography; D001853:Bone Marrow / Q000187:drug effects* / Q000201:enzymology; D001854:Bone Marrow Cells; D002247:Carbon Isotopes; D002701:Chloramphenicol / Q000494:pharmacology*; D003576:Electron Transport Complex IV / Q000378:metabolism; D004920:Erythropoiesis / Q000187:drug effects*; D007930:Leucine / Q000378:metabolism; D008854:Microscopy, Electron; D008928:Mitochondria / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D010101:Oxygen Consumption; D010659:Phenylhydrazines; D011817:Rabbits
D002247:Carbon Isotopes; D010659:Phenylhydrazines; D002701:Chloramphenicol; D003576:Electron Transport Complex IV; D007930:Leucine