Increased cholesterol epoxide hydrolase activity in clofibrate-fed animals

Area of Science:

• Biochemistry
• Pharmacology
• Enzymology

Background:

• Cholesterol epoxide hydrolase (mCE) is a key enzyme in cholesterol metabolism.
• mCE catalyzes the conversion of cholesterol epoxides (CE) to cholestanetriol (CT).
• Understanding mCE regulation is crucial for metabolic research.

Purpose of the Study:

• To investigate the effect of xenobiotics on hepatic mCE activity.
• To determine if hypolipidemic agents influence mCE levels.
• To explore the impact of clofibrate on mCE activity in different tissues and subcellular fractions.

Main Methods:

• Measurement of hepatic mCE activity in mice pretreated with various xenobiotics.
• Dietary administration of phenoxyacetate hypolipidemics (clofibrate, ciprofibrate) for 14 days.
• Analysis of mCE activity in rabbit hepatic and renal tissues, and subcellular fractions (nuclear, mitochondrial, cytosolic).

Main Results:

• Only phenoxyacetate hypolipidemics (clofibrate, ciprofibrate) significantly increased hepatic mCE activity (1.8-fold).
• Clofibrate administration elevated rabbit hepatic (2.9-fold) and rat/rabbit renal (1.5- to 2.3-fold) mCE activity.
• In rabbits, clofibrate increased nuclear and light mitochondrial mCE activity but not cytosolic or heavy mitochondrial fractions.

Conclusions:

• Phenoxyacetate hypolipidemics are potent inducers of mCE activity.
• Clofibrate enhances cholesterol epoxide hydrolysis in hepatic and renal tissues.
• Increased mCE activity may elevate tissue cholestanetriol levels, potentially linking to hypocholesterolemic mechanisms.