Effect of clofibrate and 1-methyl-4-piperidyl bis (p-chlorophenoxy) acetate (Sandoz 42–348) on steroid and drug metabolism by rat liver microsomes

Effects of clofibrate on the metabolism of progesterone and oestradiol in rat liver microsomal fraction

“…Previous reports (Salvador et al, 1970;) and the present study have shown that clofibrate influences the metabolism ofvarious steroid hormones in rat liver. As this drug is a commonly used hypolipidaemic agent it would be of great interest to study further its influence on the steroid metabolism in man.…”

“…Several studies indicate that clofibrate belongs to the group of drugs that stimulates the activity of a variety of hepatic microsomal drug-metabolizing enzymes (Best & Duncan, 1964;Hess et al, 1965;Salvador et al, 1970). Clofibrate influences the metabolism of androstenedione in the rat liver by enhancing all hydroxylation reactions and the activity of 17fi-hydroxy steroid reductase.…”

“…Clofibrate treatment increases liver weight (Best & Duncan, 1964), induces proliferation of smooth-surfaced endoplasmic reticulum in rat liver cells (Hess et al, 1965) and increases cytochrome P-450 content in rat liver microsomal fraction (Salvador et al, 1970). Clofibrate also stimulates the liver hydroxylation of testosterone (Salvador et al, 1970). These effects of clofibrate may all be explained by the induction of drugmetabolizing hepatic microsomal enzymes.…”

Dietary clofibrate inhibits induction of hepatic antioxidant enzymes by chronic estradiol in female ACI rats

“…Peroxisomal CAT is induced by clofibrate treatment but not in sufficient amounts to neutralize the excess H 2 O 2 produced by ACO induction (Nilakantan et al, 1998). In addition, the induction of CYP450-dependent metabolism of fatty acids and other endogenous substrates by peroxisome proliferators is another source of reactive oxygen species (ROS) (Salvador et al, 1970;Einarsson et al, 1973). Reactive catechol metabolites of E 2 (CEs), in particular 4-OH-E 2 , undergo redox cycling to form reactive quinones that are implicated in mammary carcinogenesis (Li et al, 2004).…”

Effects of clofibrate on some microsomal hydroxylations involved in the formation and metabolism of bile acids in rat liver

“…Earlier works have shown that clofibrate increases liverweight (Best & Duncan, 1964), induces proliferation of smooth-surfaced endoplasmic reticulum in rat liver cells (Hess et al, 1965) and increases the content of cytochrome P4SO in rat liver microsomal fraction (Salvador et aL, 1970;Lewis et al, 1974). Clofibrate influences hepatic drug metabolism in rats (Lewis et al, 1974) and alters the metabolism of several steroid hormones, e.g.…”