It has been reported that the liver intoxication by CCl
4 is primarily caused from damages in mitochondrial functions. The present systematic investigation revealed some changes in mitochondrial functions, and the results are presented as follows.
With mitochondria isolated from the liver of rat with CCl
4 intoxication an investigation was carried out on changes of the energy metabolism on the lipid peroxidation which is thought to have an important bearing on the onset of liver damages, as well as on changes of related substances. Simultaneously, changes in mitochondria isolated from normal rat liver were studied in vitro in the presence of CCl
4. For the intoxication group the mixture of 0.4ml CCl
4 and 1.6ml salad oil was injected into the rat peritoneal cavity and the liver was taken out of the animal 16 hours later when CCl
4-intoxication was most marked, and mitochondria were isolated to be used for the experiment. For the control group 2.0ml salad oil alone was injected intraperitoneally, and mitochondria isolated from the liver taken out 16 hours later were used. In the in vitro experiment the mitochondria isolated from normal rat liver served for this purpose. The results may briefly summarized as follows: 1) In the CCl
4-intoxicated liver the dehydrogenase system of mitochondria is most markedly damaged. 2) The energy conversion system is so damaged that the ATP synthesis is markedly decreased. 3) Ion-transport system which acts synergistically with the energy conversion of early stage is damaged. 4) The lipid peroxidation induced by Fe
2+ is markedly diminished. 5) The phospholipid content of mitochondria and arachidoic acid content of phospholipid are decreased, while the content of tryglyceride is increased. 6) CCl
4 acts on the oxidative phosphrylation of the normal rat liver counter-synergistically, though only weakly. 7) When CCl
4 is added to normal rat liver in vitro, the lipid peroxidation is enhanced, on the contrary to the situation of CCl
4-intoxicated rat liver. These findings suggest that the onset mechanisms of mitochonrial functional disturbances may be explained as due to the damage to the mitochondrial membrane, the damage to the membrane system and energy metabolic system brought about by CCl
4 as well as by the by-products of membrane disintegration.
View full abstract