Effects of Clofibrats on Carbon Tetrachloride Induced Fatty Liver in Rats-With Special Reference to liver Triglycerides-

Abstract

In 1962, Thorp and Waring!) reported that administration in rats of clofibrate (ethyl 2( p - chlorophenoxy)-2-methylpropionate= ethyl p-chlorphenoxyisobutyrate, Atromid-S, see Fig. 1) and the combination of clofibrate with androsterone (Atromid)reduced the plasma cholesterol level. Later in the same year OIiver2) showed that Atromid lowered elevated serum cholesterol and triglycerides (TG) levels in man. Subsequently, however3) , Oliver himself demonstrated that the administration of clofibrate alone was as effective as Atromid. Since these earlier papers , considerably more experience has been gained concerning the effect of clofibrate, and now it seems well established that clofibrate decrease plasma levels both of TG and cholesterol in humans and rats although the mechanism of this effect has not been fully defined. The active form of clofibrate in vivo seems to be the free chlorophenoxyisobutyric am] (C. P. I. E ) bound to albumin 4) On the other hand, the induction of a fatty liver in experimental animals following the administration of carbon itetrachloride (CCI4) has been amply documented5- 7) . The etiology for the accumulation of hepatic fats by CC14 has not been settled5) , but chemical investigation revealed that the rise in liver lipids following CCI4 was primarily due to increased hepatic TG6). Most studies field in the past aimed at obtaining the greater knowledge regarding mechanism by which human liver damage is produced, but in recent years this model has been used in study of lipid, especially TG, metabolism8 9) At the present time available evidences support the hypothesis that such an accumulation of lipids in liver tissue by CC14 is due to a block in the transfer of TG from the liver to the plasma!O, 14) • Thus clofibrate and carbon tetrachloride both undoubtedly produce wide spread effect on lipid metabolism in living organism. It would be most interesting at this stage to see the effects of clofibrate on liver lipids, especially TG, of CCI4 intoxicated rats, which may help for the elucidation of mechanisms involved in the action of clofibrate as well as that of CC1 4•