Kuzelová Magdaléna, Adameová Adriana, Sumbalová Zuzana, Paulíková Ingrid, Harcárová Anna, Svec Pavel, Kucharská Jarmila
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Comenius University, Odbojárov 10, 832 32 Bratislava, Slovakia.
Gen Physiol Biophys. 2008 Dec;27(4):291-8.
The effect of simvastatin administered for 10 days on coenzyme Q and antioxidant/oxidant balance in a rat model of diabetes mellitus and hypercholesterolaemia was studied. In the diabetic-hypercholesterolaemic rats the signs of oxidative stress-decreased alpha-tocopherol/cholesterol in the plasma (p < 0.01) and alpha-tocopherol in liver (p < 0.001) together with increased lipid peroxidation in the liver (TBARS, p < 0.05) were found. Increased coenzyme Q9 concentrations in the plasma (p < 0.05) and liver (p < 0.01), coenzyme Q10 in the myocardium (p < 0.05) and in the liver (p < 0.01) may indicate adaptation to oxidative stress. Administration of simvastatin (10 mg/kg) to the diabetic-hypercholesterolaemic rats counteracted increased myocardial (coenzyme Q10, p < 0.05) and liver (total coenzyme Q9, p < 0.05) coenzyme Q concentrations but did not improve alpha-tocopherol depletion and increased formation of TBARS in the liver. Even though simvastatin treatment did not induce coenzyme Q deficiency in plasma, heart and liver of the diabetic-hypercholesterolaemic rats as compared to the control levels, it was not able to prevent completely the changes in antioxidant/oxidant balance induced by diabetes and hypercholesterolaemia. The results highlight the importance of studying the effect of statins on the coenzyme Q levels in the animal models of pathological conditions known to change the initial antioxidant defence system.
研究了辛伐他汀连续给药10天对糖尿病和高胆固醇血症大鼠模型中辅酶Q及抗氧化/氧化平衡的影响。在糖尿病合并高胆固醇血症大鼠中，发现氧化应激迹象——血浆中α-生育酚/胆固醇降低（p < 0.01），肝脏中α-生育酚降低（p < 0.001），同时肝脏中脂质过氧化增加（TBARS，p < 0.05）。血浆（p < 0.05）和肝脏（p < 0.01）中辅酶Q9浓度升高，心肌（p < 0.05）和肝脏（p < 0.01）中辅酶Q10浓度升高，可能表明机体对氧化应激的适应。给糖尿病合并高胆固醇血症大鼠服用辛伐他汀（10 mg/kg）可抵消心肌（辅酶Q10，p < 0.05）和肝脏（总辅酶Q9，p < 0.05）中辅酶Q浓度的升高，但并未改善α-生育酚的消耗，也未抑制肝脏中TBARS的生成增加。尽管与对照水平相比，辛伐他汀治疗并未导致糖尿病合并高胆固醇血症大鼠血浆、心脏和肝脏中辅酶Q缺乏，但它无法完全预防糖尿病和高胆固醇血症引起的抗氧化/氧化平衡变化。这些结果凸显了在已知会改变初始抗氧化防御系统的病理状况动物模型中研究他汀类药物对辅酶Q水平影响的重要性。
