Effects of lovastatin and pravastatin on ubiquinone and 4-hydroxynonenal tissue levels in the hypercholesterolemic hamster

Results of a previous experiment suggested that lovastatin treatment leads to a larger decrease of ubiquinone levels in rat tissues than does treatmen t with pravastatin. We attempted to confirm our previous findings in the hy percholesterolemic hamster, a model that mimics the cholesterol regulatory mechanisms in humans. In view of the proposed antioxidant role of ubiquinon e, we also tested the hypothesis that decreases in ubiquinone levels would be associated with an increase in peroxidation products-4-hydroxynonenal (H NE) and one of its major metabolites, 1,4-dihydroxynonene (DHN)-in the myoc ardium. Lovastatin and pravastatin were administered at a dosage of 20 mg/k g per day for 30 days to male Golden Syrian hamsters fed a hypercholesterol emic diet. In the blood, myocardium, and skeletal muscle, decreases in ubiq uinone-9 (Q(9)) levels were observed with both drugs (ranging from 29% to 4 2%). In the liver, no effects were observed in Q(9) levels versus the contr ol group, whereas the difference between the treatment groups was significa nt. No differences were seen in ubiquinone-10 (Q(10)) levels in the blood, myocardium, or skeletal muscle. In the liver, significant decreases versus the control group (21% for lovastatin and 14% for pravastatin) mere seen in Q(10) levels. For lovastatin and pravastatin, similar decreases in protein -bound HNE (15% and 35%, respectively) and DHN (21% and 25%, respectively) were observed in the myocardium; changes in both treatment groups were sign ificantly greater than in the control group. Our results support previous r eports indicating that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhi bitors decrease ubiquinone tissue levels. However, the decrease was similar with lovastatin and pravastatin, contrary to what had been observed previo usly in the rat. The HNE results do not confirm our hypothesis on the antio xidant activity of ubiquinone in the myocardium but rather suggest, for lov astatin and pravastatin, an additional preventive effect on the progression of atherosclerosis.