MECHANISM OF THE FORMATION OF MEGAMITOCHONDRIA IN THE MOUSE-LIVER INDUCED BY CHLORAMPHENICOL

Correlation between chloramphenicol-induced formation of megamitochond ria in the mouse liver and oxidative stress was studied by lipid perox idation analysis and electron microscopic technique. Chloramphenicol s uppressed increases in the body weight and liver weight of experimenta l 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 st ayed at the same levels as those of the control, and the formation of megamitochondria was completely suppressed. Allopurinol, a xanthine ox idase (EC 1.2.3.2) inhibitor, partly inhibited the changes induced by chloramphenicol, as described above. These results suggest that chlora mphenicol-induced formation of megamitochondria is not simply ascribed to the suppression of the dividing process of mitochondria due to low ered protein synthesis in mitochondria but is intimately related to ox idative stress. Furthermore, the results obtained with allopurinol may indicate that enhanced levels of lipid peroxidation observed in chlor amphenicol-treated animals are partly due to enhanced rate of the degr adation of purine nucleotides catalyzed by xanthine oxidase.