ABSTRACT
Clofibrate treatment also decreased plasma triglyceride levels in male hamsters (Figure 19.4). However, although terminal plasma levels of clofibric acid in the hamster were similar to those in the rat and greater than in the mouse, there was no significant effect of treatment on the hepatic activity of cyanide -insensitive palmitoyl-CoA oxidation. There was also no effect of treatment on the activity of mitochondrial a-GPDH in hamster liver. The results suggest that peroxisome proliferation is not essential for the hypotriglyceridaemic properties of clofibrate, at least in the hamster. Dissociation of hypolipidaemic action and peroxisome proliferation was also seen in studies in the rat with the clofibrate analogue bezafibrate (Lazarow et al., 1982). In these experiments, low doses of bezafibrate reduced plasma cholesterol and triglyceride without any change in peroxisome enzymes. Experiments with tiadenol, which is not structurally related to clofibrate produced similar results (Facino et al., 1987). The lack of effect of clofibrate on hamster peroxisomes indicated that this compound does not produce peroxisome proliferation in all rodent species. However, in other studies (Reddy et al., 1982), clofibrate treatment did cause a small increase in the activity of cyanide -insensitive palmitoyl-CoA oxidation in the hamster. In this study the maximum increase in enzyme activity induced by clofibrate treatment was two-fold compared with the 18fold increase in a rat study reported by Lake et al. (1983) and the 28-fold increase seen in the rat study described here. Other compounds including clobuzarit (Orton et al., 1984), di-(2-ethylhexyl) phthalate, mono-(2-ethylhexyl)phthalate (Lake et al., 1983), fenofibrate and methylclofenapate (Reddy et al., 1982) do cause some increase in the activity of cyanide -insensitive palmitoyl-CoA oxidation in the hamster, although in every case the extent of peroxisome proliferation (as judged by enzyme activity) is less than in rats treated with a similar dose of the compound.
