Effects of Lovastatin and Pravastatin on ubiquinone and 4- hydroxynonenal tissue levels in the hypercholesterolemic hamster”

Further to our experiment which suggested that lovastatin treatment leads to a larger decrease of ubiquinone levels in rat tissues than pravastatin, we undertook to confirm this finding in the hypercholesterolemic hamster, a model that mimics the cholesterol regulatory mechanisms in humans. In view of the proposed antioxidant role of ubiquinone, we also tested the hypothesis that ubiquinone level decreases would be associated with an increase in peroxidation products, i.e. 4-hydroxynonenal (HNE), and one of its major metabolite, 1,4dihydroxynonene (DHN) in the myocardium. Methods: Lovastatin and pravastatin were administered at a dose of 20 mg/kg/day for 30 days to male Golden Syrian hamsters fed a hypercholesterolemic diet. Results: In blood, myocardium and skeletal muscle decreases in Q9 levels were observed with both drugs (29% to 42%, p<0.05). In the liver, no effects were observed in Q9 levels vs. control while the difference between the treatment groups was significant. No differences were seen in ubiquinone-10 (Q10) levels in the blood, myocardium , or skeletal muscle. In the liver, significant decrease vs. control (21% for lovastatin and 14% for pravastatin, p<0.05) were observed in Q10 levels. For lovastatin and pravastatin similar decreases in protein-bound HNE (15% and 35% respectively, p<0.05 overall) and DHN (21% and 25% respectively, p<0.05 overall) were observed in myocardium. Conclusions: Our results support previous reports indicating that HMG-CoA reductase inhibitors decrease ubiquinone tissue levels. However, this decrease was similar with lovastatin and pravastatin contrary to what was observed in the rat. The HNE results do not confirm our hypothesis on the antioxidant activity of ubiquinone in the myocardium but rather suggest for lovastatin and pravastatin, an additional preventive effect on the progression of atherosclerotis.