Mechanism of the formation of megamitochondria in the mouse liver induced by chloramphenicol.

Correlation between chloramphenicol-induced formation of megamitochondria in the mouse liver and oxidative stress was studied by lipid peroxidation analysis and electron microscopic technique. Chloramphenicol suppressed increases in the body weight and liver weight of experimental animals and at the same time induced a remarkable increase in lipid peroxidation in the liver during the formation of megamitochondria. A spin trapping agent, 4-hydroxy-2,2,6,6-tetramethyl-piperidine-1-oxyl, abolished all these changes induced by chloramphenicol. Namely, both the body weight and liver weight of chloramphenicol-treated animals stayed at the same levels as those of the control, and the formation of megamitochondria was completely suppressed. Allopurinol, a xanthine oxidase (EC 1.2.3.2) inhibitor, partly inhibited the changes induced by chloramphenicol, as described above. These results suggest that chloramphenicol-induced formation of megamitochondria is not simply ascribed to the suppression of the dividing process of mitochondria due to lowered protein synthesis in mitochondria but is intimately related to oxidative stress. Furthermore, the results obtained with allopurinol may indicate that enhanced levels of lipid peroxidation observed in chloramphenicol-treated animals are partly due to enhanced rate of the degradation of purine nucleotides catalyzed by xanthine oxidase.