Antioxidant Effects of Statins in Patients with Atherosclerotic Cerebrovascular Disease
Journal of Clinical Neurology 2014³â 10±Ç 2È£ p.140 ~ p.147
¹®°æÁØ(Moon Gyeong-Joon) - Sungkyunkwan University School of Medicine Medical Research Institute
±è¼®Àç(Kim Suk-Jae) - Sungkyunkwan University School of Medicine Samsung Medical Center Department of Neurology
Á¶¿¬Èñ(Cho Yeon-Hee) - Samsung Biomedical Research Institute Clinical Research Center
(Ryoo Soo-Kyung) - Sungkyunkwan University School of Medicine Samsung Medical Center Department of Neurology
¹æ¿À¿µ(Bang Oh-Young) - Sungkyunkwan University School of Medicine Samsung Medical Center Department of Neurology
Abstract
Background and Purpose: Oxidative stress is involved in the pathophysiological mechanisms of stroke (e.g., atherosclerosis) and brain injury after ischemic stroke. Statins, which inhibit 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, have both pleiotropic and low-density lipoprotein (LDL)-lowering properties. Recent trials have shown that high-dose statins reduce the risk of cerebrovascular events. However, there is a paucity of data regarding the changes in the oxidative stress markers in patients with atherosclerotic stroke after statin use. This study evaluated changes in oxidative stress markers after short-term use of a high-dose statin in patients with atherosclerotic stroke.
Methods: Rosuvastatin was administered at a dose of 20 mg/day to 99 patients who had suffered an atherosclerotic stroke and no prior statin use. Blood samples were collected before and 1 month after dosing, and the serum levels of four oxidative stress markers-malondialdehyde (MDA), oxidized LDL (oxLDL), protein carbonyl content (PCO), and 8-hydroxy-2¡¯-deoxyguanosine (8-OHdG)-were evaluated to determine the oxidation of MDA and lipids, proteins, and DNA, respectively, at both of those time points.
Results: The baseline levels and the degrees of reduction after statin use differed among the oxidative stress markers measured. MDA and PCO levels were associated with infarct volumes on diffusion-weighted imaging (r=0.551, p<0.05, and r=0.444, p=0.05, respectively). Statin use decreased MDA and oxLDL levels (both p<0.05) but not the PCO or 8-OHdG level. While the reduction in MDA levels after statin use was not associated with changes in cholesterol, that in oxLDL levels was proportional to the reductions in cholesterol (r=0.479, p<0.01), LDL (r=0.459, p<0.01), and apolipoprotein B (r=0.444, p<0.05).
Conclusions: The impact of individual oxidative stress markers differs with time after ischemic stroke, suggesting that different oxidative markers reflect different aspects of oxidative stress. In addition, short-term use of a statin exerts antioxidant effects against lipid peroxidation via lipid-lowering-dependent and -independent mechanisms, but not against protein or DNA oxidation in atherosclerotic stroke patients.
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atherosclerosis, ischemic stroke, statin, oxidative stress, cholesterol
KMID :
1130620140100020140
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