Reference

Concomitant induction of cytosolic but not microsomal epoxide hydrolase with peroxisomal b-oxidation by various hypolipidemic compounds

Concomitant induction of cytosolic but not microsomal epoxide hydrolase with peroxisomal b-oxidation by various hypolipidemic compounds. Schladt, Ludwig; Hartmann, Renate; Timms, Christopher; Strolin-Benedetti, M.; Dostert, P.Several substances are used for example 50-78-2 and 4238-71-5 which are their cas registry numbers.; Woerner, Walter; Oesch, Franz (Inst. Toxikol., Univ. Mainz, Mainz D-6500, Fed. Rep. Ger.). Biochem. Pharmacol., 36(3), 345-51 (English) 1987. CODEN: BCPCA6. ISSN: 0006-2952. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) The effects of two cholesterol-lowering (probucol [23288-49-5] and 1-benzylimidazole [4238-71-5]), three triglyceride- and cholesterol-lowering (clofibrate [637-07-0], tiadenol [6964-20-1] and fenofibrate [49562-28-9]) and one triglyceride-lowering acetylsalicylic acid [50-78-2]) compds. on the specific activities of two lipid-metabolizing enzymes (cyanide-insensitive peroxisomal b-oxidn. system and palmitoyl-CoA hydrolase [9025-87-0]) and two xenobiotic metabolizing enzymes [cytosolic (cEH) and microsomal (mEHb) epoxide hydrolase [9048-63-9]] from the livers of rats were investigated. With the exception of probucol and acetylsalicylic acid, all compds. tested caused a dose-dependent hepatomegaly. Taken on a wt. basis fenofibrate was the most effective inducer, causing a 20-fold induction of peroxisomal b-oxidn., a 13-fold induction of cEH activity and a 16-fold induction of palmitoyl-CoA hydrolase activity. The other compds. with triglyceride-lowering activity also induced cEH as well as peroxisomal b-oxidn. and palmitoyl-CoA hydrolase activity. The potency of each individual drug was similar for induction of cEH activity as compared with that of peroxisomal b-oxidn. and palmitoyl-CoA hydrolase activity, but very dissimilar for mEHb, which upon treatment with any of the triglyceride-lowering compds. was either not or only minimally (<1.5-fold) induced. 1-Benzylimidazole possessing exclusively cholesterol-lowering activity increased mEHb much more than either cEH or peroxisomal b-oxidn. The absence of an enhancement of cEH activity in in vitro studies confirmed that the increase in enzyme activity by the test compds. is not caused by activation. CEH activity was also induced in the kidney but only about 2-fold by fenofibrate, tiadenol and acetylsalicylic acid. With hypolipidemic drugs varying in their peroxisome-proliferating potency from inactive to very potent, the effects on peroxisomal b-oxidn. and cEH were similar in all instances, whilst the effects on mEHb could be clearly dissocd. Thus, in the rat a concomitant regulation of cEH with peroxisomal b-oxidn. and peroxisome proliferation by hypolipidemic drugs becomes apparent. .

Effect of hypolipidemic drugs on the enzyme activities of purine nucleotide degradation pathways

Effect of hypolipidemic drugs on the enzyme activities of purine nucleotide degradation pathways.Some chemicals with cas registry numbers like 9026-93-1 and 54504-70-0 are also used. Lazarova, Perla; Rendekova, Viera; Chandoga, Jan; Zak, Ivan; Hlavenkova, Emilia; Pechan, Ivan (Fac. Med., Comenius Univ., Bratislava 811 08, Czech.). Biologia (Bratislava), 41(12), 1167-72 (English) 1986. CODEN: BLOAAO. ISSN: 0006-3088. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) The hypolipemic drugs acetylsalicylic acid [50-78-2], fenofibrate [49562-28-9], etofylline clofibrate [54504-70-0], and bezafibrate [41859-67-0] (mixed with the std. lab. diet for 15 days) inhibited adenosine deaminase [9026-93-1] in the livers but not in the brains of rats. Hepatic xanthine dehydrogenase [9054-84-6] was also inhibited by the drugs. Brain membrane-bound 5'-nucleotidase [9027-73-0] was inhibited by fenofibrate and etofylline clofibrate but not by the other drugs. Hepatic purine nucleoside phosphorylase [9030-21-1] was inhibited by fenofibrate but not by the other drugs. .