The mechanism of CCl
4-induced fatty liver was investigated, studying biochemical changes and phospholipid metabolism in mitochondria and microsomes of CCl
4-poisoned rat liver. Rats were sacrificed 2, 4, 8, 12 and 24 hours after the intraperitoneal administration of CCl
4.
The mitochondrial respiratory control was intact during the first 8 hours of intoxication, but disturbed in 12 hours. The mitochondrial oxidative phosphorylation was disturbed 24 hours after the injection of CCl
4.
Changes in the fatty acid composition of mitochondrial phospholipids occurrd 12 hours after CCl
4-injection when the mitochondrial respiratory control began to be disturbed. These changes became remarkable thereafter: arachidonic acid decreased, palmitic, stearic and oleic acid increased.
On the other hand the fatty acid composition of microsomal phospholipids changed in earlier stage, already 2 hours after CCl
4-injection and became remarkable during the course of poisoning: arachidonic acid decreased, palmitic, oleic and linoleic acid increased. The changes of the fatty acid composition of microsomal phospholipids were coincident with the decrease of cytochrome b
5 and P-450. The changes of fatty acid patterns in the phospholipids correspond with the increase of neutral fat in the fatty liver and have intimate relation with the functional depression due to the destruction of integrity of the subcellular particles.
From above data it is suggested that CCl
4-administraction causesthe destruction of the integrity of subcellular particles in situ and that, therefore, microsomal changes are the primary cause of the fatty liver induced by CCl
4.
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