J Clin Neurol.  2014 Apr;10(2):140-147. 10.3988/jcn.2014.10.2.140.

Antioxidant Effects of Statins in Patients with Atherosclerotic Cerebrovascular Disease

Affiliations
  • 1Medical Research Institute, Sungkyunkwan University School of Medicine, Suwon, Korea.
  • 2Clinical Research Center, Samsung Biomedical Research Institute, Seoul, Korea.
  • 3Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. nmboy@unitel.co.kr
  • 4Samsung Advanced Institute for Health Sciences and Technology, Seoul, Korea.

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.

Keyword

atherosclerosis; ischemic stroke; statin; oxidative stress; cholesterol

MeSH Terms

Antioxidants*
Apolipoproteins
Atherosclerosis
Brain Injuries
Cholesterol
Coenzyme A
DNA
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors*
Lipid Peroxidation
Lipoproteins
Oxidative Stress
Oxidoreductases
Stroke
Rosuvastatin Calcium
Antioxidants
Apolipoproteins
Cholesterol
Coenzyme A
DNA
Lipoproteins
Oxidoreductases

Figure

  • Fig. 1 Correlations between oxidative stress markers and lesion volume on initial DWI in acute stroke patients. Individual values and the linear regression line are displayed. DWI: diffusion-weighted imaging, MDA: malondialdehyde, oxLDL: oxidized low-density lipoprotein, PCO: protein carbonyl content, 8-OHdG: 8-hydroxy-2'-deoxyguanosine.

  • Fig. 2 The changes in oxidative stress markers before and after statin use. A: Rosuvastatin significantly reduced serum MDA levels in the acute stroke group but not in the chronic stroke group. B: There was a marked reduction in serum oxLDL level in both the acute and chronic stroke groups. C: There was no significant change in PCO in either stroke group after statin use. D: Surprisingly, 8-OHdG levels increased more in the acute stroke group than in the chronic stroke group after statin use. *p<0.05, **p<0.01. MDA: malondialdehyde, oxLDL: oxidized low-density lipoprotein, PCO: protein carbonyl content, Post-Tx: posttherapy, Pre-Tx: before therapy, 8-OHdG: 8-hydroxy-2'-deoxyguanosine.

  • Fig. 3 Correlation between changes in the levels of lipids and markers of oxidative stress. Black circle and white triangle signify acute and chronic stroke patients, respectively. Individual values and linear regression lines are displayed. LDL: low-density lipoprotein, MDA: malondialdehyde, oxLDL: oxidized low-density lipoprotein.


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Bum Joon Kim, Hyun Goo Kang, Sang-wook Lee, Jinhong Jung, Min-Hwan Lee, Dong-Wha Kang, Jong S. Kim, Sun U. Kwon
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