Differential long-term effects of D-chloramphenicol on the biogenesis of mitochondria in normal and regenerating rat liver.
1. Normal and partially hepatectomized rats (150g) were injected daily with d-chloramphenicol (20mg) for a period of 4 weeks, in order to investigate whether defective mitochondria could be induced in vivo in higher organisms as in yeast, and to measure the degree of inhibition of the mitochondrial function thus obtained. 2. The antibiotic did not affect growth and increased the amount of liver protein without changing the mitochondrial yield. 3. The respiration of isolated mitochondria from regenerated liver (regeneration completed) with succinate, alpha-oxo-glutarate, isocitrate and malate, was decreased in the chloramphenicol-treated rats, whereas in normal liver the antibiotic increased the mitochondrial oxygen consumption with succinate and did not significantly change the respiration with other substrates. 4. Mitochondrial cytochromes and respiratory enzymes were also decreased in amount in regenerated liver from the treated rats and enhanced in normal liver. 5. The protein specific radioactivities of most mitochondrial and microsomal subfractions, 30min after an injection of [(14)C]leucine, were decreased in regenerated liver under the action of chloramphenicol. Conversely, the incorporation of [(14)C]leucine into proteins of most subfractions in incubations of liver slices was enhanced in the case of normal rats treated with the antibiotic. 6. It is concluded that in regenerated liver chloramphenicol induces functionally defective mitochondria by inhibiting their biogenesis, whereas in normal liver the stimulation of respiration and protein synthesis is probably a secondary detoxication response.
D000818:Animals; D002247:Carbon Isotopes; D002701:Chloramphenicol / Q000494:pharmacology*; D002951:Citrates; D003580:Cytochromes / Q000032:analysis; D005977:Glutarates / Q000378:metabolism; D006498:Hepatectomy; D066298:In Vitro Techniques; D007930:Leucine / Q000378:metabolism; D008115:Liver Regeneration / Q000187:drug effects*; D008293:Malates / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000032:analysis; D008928:Mitochondria / Q000201:enzymology; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D010101:Oxygen Consumption; D011506:Proteins / Q000032:analysis; D051381:Rats; D013386:Succinates / Q000378:metabolism
D002247:Carbon Isotopes; D002951:Citrates; D003580:Cytochromes; D005977:Glutarates; D008293:Malates; D011506:Proteins; D013386:Succinates; D002701:Chloramphenicol; D007930:Leucine