Role of thyroid state on induction by ciprofibrate of laurate hydroxylase and peroxisomal enzymes in rat liver microsomes.

The effects of hypothyroidism and hyperthyroidism upon liver microsomal omega-laurate hydroxylase activity (cytochrome P450 IV A1-dependent), peroxisome proliferation marker enzyme activities and acyl CoA oxidase (AOX) expression induced by ciprofibrate (2 mg/kg/day during 8 days) were studied in the male Wistar rat so as to clarify firstly the possible involvement of thyroid hormones in the modification of peroxisomal ciprofibrate-induced enzyme activities in relation to hepatic microsomal cytochrome P450 IV A1 induction, and secondly the possible direct effect of thyroid hormones on the gene expression of specific peroxisomal enzymes. No significant change was found in the ciprofibrate-induced omega-laurate hydroxylase activity in hypothyroid rats or in rats that had received a large dose of triiodothyronine (LT3), suggesting that the thyroid hormone does not interfere with the peroxisome proliferation process through such an indirect mechanism. The induction by ciprofibrate [2-(4-(2-2dichlorocyclopropyl)phenoxyl-2methyl-propion ic acid)] of mitochondrial alpha-glycerolphosphate dehydrogenase and microsomal bilirubin UDPGT was decreased about 3-fold and 1.

Effects of simvastatin, a lipoprotein-lowering drug, on the hepatic enzymes involved in drug metabolism in the Wistar rat.

1. Simvastatin, a competitive inhibitor of 3-hydroxy-3-methyl glutaryl CoA reductase, lowers the plasma cholesterol level and has been approved for treatment of hyperlipoproteinaemia. 2.

Comparative and simultaneous effects of simvastatin and ciprofibrate on plasma lipid parameters and upon hepatic drug metabolizing and peroxisome proliferation marker enzymes in the male Wistar rat.

The effects of an associated treatment with Ciprofibrate and Simvastatin upon plasma lipid parameters, liver Mixed Function Oxidases enzymes and peroxisomal markers have been studied in male Wistar rats. The association was efficient upon triglycerides, but not upon cholesterol. The inducive and proliferative effects commonly exerted by Ciprofibrate (5 mg/kg/day) were not significantly modified by the simultaneous treatment with Simvastatin (10 mg/kg/day).

Nutritional factors of microsomal enzymatic induction: influence of lipidic components of the diet.

We compared the ability of two different diets containing 6 per cent of maize oil and 6 per cent of fish oil to modify: firstly the enzyme induction by phenobarbital and secondly the phenobarbital hydroxylation by the liver either in vivo or during in vitro perfusions. The presence of fish oil in the diet increased the cyt P 450 content and the bilirubin glucuronosyl transferase activity. The two induction effects promoted by the association of the phenobarbital treatment and the eating of the fish oil were not additive and it was found that the phenobarbital induction effect was decreased by the fish oil consumption.

Differential action of thyroid hormones and chemically related compounds on the activity of UDP-glucuronosyltransferases and cytochrome P-450 isozymes in rat liver.

The effect of thyroid hormones and chemically related compounds, on the activity of UDP-glucuronosyltransferases (EC 2.4.1.