Effects of some hypolipidemic agents on biochemical values and hepatic peroxisomal enzymes in rats: comparison of probucol, CGA, KCD-232, MLM-160, AL-369 and clinofibrate with clofibrate.
The effect of some hypolipidemic agents, which are commercially available and those being developed, on certain biochemical values and on hepatic peroxisomal enzyme activities of rats were examined. Clofibrate (0.25% (w/w) in the diet), p-chlorophenoxy-isobutyryl-glycinamide (CGA) (0.25%), clinofibrate (0.1%), KCD-232 (0.1%) and MLM-160 (0.1%) increased the activities of peroxisomal fatty acyl-CoA oxidizing system, carnitine acetyltransferase, and mitochondrial carnitine palmitoyltransferase. Of peroxisomal enzymes, catalase activity was increased by the above agents, whereas the activities of D-amino acid oxidase and urate oxidase were decreased by clofibrate and CGA, and but were increased by KCD-232 and MLM-160 which are structurally unrelated to clofibrate. No influence on these enzyme activities by AL-369 and probucol treatments were observed. Hepatomegaly was induced by clofibrate, CGA, KCD-232 and MLM-160. Concerning serum lipid levels, clofibrate, CGA, clinofibrate, KCD-232 and MLM-160 decreased both cholesterol and triglyceride levels, whereas probucol decreased only cholesterol level. AL-369 had no influence on serum lipid levels under this condition using normolipemic rat. From these results, it was concluded that differing clofibrate and CGA, clinofibrate, MLM-160 and KCD-232 might not induce peroxisome proliferation in hepatic cells, although these have an influence on the enzyme composition of hepatic peroxisomes.
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002994:Clofibrate / Q000494:pharmacology; D006016:Glycolates / Q000494:pharmacology*; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D008055:Lipids / Q000097:blood; D008099:Liver / Q000187:drug effects*; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced; D008297:Male; D008830:Microbodies / Q000187:drug effects / Q000201:enzymology; D009539:Nicotinic Acids / Q000494:pharmacology*; D010642:Phenoxyacetates / Q000494:pharmacology*; D011341:Probucol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D006016:Glycolates; D000960:Hypolipidemic Agents; D008055:Lipids; D009539:Nicotinic Acids; D010642:Phenoxyacetates; C006231:clinofibrate; C042413:4-(4'-chlorobenzyloxy)benzyl nicotinate; D002994:Clofibrate; D011341:Probucol