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Antioxidant effects of statins in patients with atherosclerotic cerebrovascular disease.

Moon GJ, Kim SJ, Cho YH, Ryoo S, Bang OY - J Clin Neurol (2014)

Bottom Line: 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).

View Article: PubMed Central - PubMed

Affiliation: Medical Research Institute, Sungkyunkwan University School of Medicine, Suwon, Korea. ; Clinical Research Center, Samsung Biomedical Research Institute, 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.

No MeSH data available.


Related in: MedlinePlus

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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Figure 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.

Mentions: The mechanisms underlying the effects of rosuvastatin on oxidative stress markers were explored by assessing the correlations between changes in lipid and oxidative stress markers from the respective pretreatment levels to the posttreatment levels (Fig. 3). The posttreatment reduction of MDA levels was not associated with the observed changes in cholesterol levels (Fig. 3C and D). Conversely, significant positive correlations were observed between the changes in oxLDL levels and those in total cholesterol (r=0.479, p<0.01), LDL (r=0.459, p<0.01), and ApoB (r=0.444, p<0.05), suggesting a lipid-lowering-dependent reduction in serum oxLDL (Fig. 3A and B). Rosuvastatin had no effect on serum PCO and 8-OHdG levels (data not shown).


Antioxidant effects of statins in patients with atherosclerotic cerebrovascular disease.

Moon GJ, Kim SJ, Cho YH, Ryoo S, Bang OY - J Clin Neurol (2014)

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.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4017017&req=5

Figure 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.
Mentions: The mechanisms underlying the effects of rosuvastatin on oxidative stress markers were explored by assessing the correlations between changes in lipid and oxidative stress markers from the respective pretreatment levels to the posttreatment levels (Fig. 3). The posttreatment reduction of MDA levels was not associated with the observed changes in cholesterol levels (Fig. 3C and D). Conversely, significant positive correlations were observed between the changes in oxLDL levels and those in total cholesterol (r=0.479, p<0.01), LDL (r=0.459, p<0.01), and ApoB (r=0.444, p<0.05), suggesting a lipid-lowering-dependent reduction in serum oxLDL (Fig. 3A and B). Rosuvastatin had no effect on serum PCO and 8-OHdG levels (data not shown).

Bottom Line: 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).

View Article: PubMed Central - PubMed

Affiliation: Medical Research Institute, Sungkyunkwan University School of Medicine, Suwon, Korea. ; Clinical Research Center, Samsung Biomedical Research Institute, 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.

No MeSH data available.


Related in: MedlinePlus