8-hydroxy-2--deoxyguanosine and Stroke

Poststroke depression is independently associated with poor health outcomes, such as increased mortality, disability, anxiety, and lower quality of life. Identifying the potential biomarkers and detailed mechanisms of poststroke depression may improve the effectiveness of therapeutic intervention. In this cross-sectional study, the authors recruited patients with subacute ischemic stroke who were consecutively admitted for neurorehabilitation. Depression was assessed with the Patient Health Questionnaire-9 (PHQ-9), with a cutoff based on a summed-items score of 10. Polysomnography and laboratory tests for oxidative stress and inflammation were arranged. In total, 139 patients (97 men [69.8%] and 42 women [30.2%]; mean age: 63.2 years [±13.4]) with recent ischemic stroke were recruited and divided into two groups based on their depressive symptoms. Body mass index (BMI), the Barthel Index, percentage of antidepressant usage, and percentage of rapid eye movement (REM) sleep differed significantly between the two groups. The PHQ-9 score was significantly correlated with the levels of total antioxidant capacity, C-reactive protein, and urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG). Urinary 8-OHdG, a marker of oxidative stress to DNA, remained significantly and positively correlated with PHQ-9 scores after adjusting for BMI, sleep-onset latency, Barthel Index, mean oxyhemoglobin saturation, age, antidepressant usage, and percentage of REM sleep by using multivariate linear regression. Depressive symptoms were related to increased oxidative DNA damage in patients with subacute ischemic stroke. Urinary 8-OHdG may serve as a potential biomarker for poststroke depression. Further longitudinal studies are needed to elucidate the causal relationship between poststroke depression and elevated oxidative stress level.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aged; Biomarkers; Brain Ischemia; C-Reactive Protein; Cross-Sectional Studies; Deoxyguanosine; Depression; DNA Damage; Female; Humans; Interleukin-6; Male; Middle Aged; Oxidative Stress; Sleep Apnea, Obstructive; Stroke; Surveys and Questionnaires

Post-stroke cognitive impairment (PSCI) is an increasingly prevalent sequel after stroke that may associate with poor functional outcome and increased risk of recurrent stroke. We aimed to explore the relationship between oxidative stress biomarkers and the presence of PSCI. 193 first-ever acute ischaemic stroke patients were consecutively enrolled in the current study. The oxidative stress biomarkers malondialdehyde (MDA) and 8-hydroxydeoxyquanosine (8-OHdG) were measured within 24 h after admission. Cognition function was evaluated by the Mini-Mental State Examination (MMSE) at 1 month after stroke. Serum levels of 8-OHdG and MDA were both significantly higher in the PSCI (p < 0.001) compared with the non-PSCI group. Both the serum levels of both 8-OHdG and MDA were negatively correlated with the MMSE score. Receiver operating characteristic curve analysis was used to evaluate 8-OHdG and MDA as markers of a high risk of PSCI and produced area under curve values of 0.700 and 0.793. Adjusted logistic regression showed that serum 8-OHdG and MDA levels remained as independent markers of PSCI. High serum levels of malondialdehyde and 8-OHdG are associated with the presence of PSCI at 1 month after stroke.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aged; Biomarkers; Cognitive Dysfunction; Deoxyguanosine; Female; Humans; Male; Malondialdehyde; Middle Aged; ROC Curve; Stroke; Time Factors

Considerable evidence suggests that periodic limb movements during sleep (PLMS) are associated with cardiovascular risk and poor stroke outcome. However, the pathogenesis for this association in stroke patients remains largely unknown.. This cross-sectional study enrolled 112 consecutive patients who were admitted to rehabilitation ward due to ischemic stroke. Polysomnography and laboratory tests for oxidative stress and inflammatory biomarkers including C-reactive protein, interleukin 6, total antioxidant capacity (TAC), and urinary 8-hydroxy-2-deoxyguanosine were conducted.. Patients were stratified into three categories according to their PLMS index. Patients in the PLMS index ≥15 group were significantly older (P = 0.011), presented a significantly higher National Institute of Health Stroke Scale at stroke onset (P = 0.032), and lower Barthel index (P = 0.035) than patients in the PLMS index <5 group. The level of TAC differed significantly (P = 0.018) among the three groups. Multivariate linear regression analyses show that the PLMS index was negatively and independently correlated with TAC (P = 0.024) in women. Besides, multivariate logistic regression analyses also reveal that patients with a PLMS index ≥15 compared with the referent PLMS index <5 had a 7.58-fold increased relative hazard for stroke recurrence (odds ratio 7.58, [1.31-43.88], P = 0.024).. This study suggests that PLMS was independently associated with decreased antioxidant capacity in women with ischemic stroke.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aged; Biomarkers; C-Reactive Protein; Cardiovascular Diseases; Deoxyguanosine; Female; Humans; Interleukin-6; Middle Aged; Nocturnal Myoclonus Syndrome; Oxidative Stress; Risk Factors; Stroke

The role of obstructive sleep apnea (OSA) in the mortality and further cardiovascular risk in subjects with ischemic stroke remains a contentious issue. Oxidative stress and inflammatory reaction due to OSA have seldom been studied in stable ischemic stroke patients.. This cross-sectional, prospective study involved 92 consecutive ischemic stroke patients who were admitted to the Rehabilitation ward. All subjects received polysomnography and laboratory tests for oxidative stress and inflammatory biomarkers, including: C-reactive protein (CRP), interleukin 6 (IL-6), total antioxidant capacity (TAC), and urinary 8-hydroxy-2-deoxyguanosine. Differences in study variables between patients with or without severe OSA were compared, and multivariate linear regression analyses were used to assess the relationship between OSA severity and target biomarkers.. Participants in the severe OSA group were significantly older (p = 0.002), had a significantly higher risk of hypertension (p = 0.021) and a lower level of CRP (p = 0.006). Among the subjects with ischemic stroke and severe OSA, the levels of CRP, IL-6, and TAC were positively correlated with the desaturation index (DI) and the TAC levels were negatively correlated with mean arterial oxygen saturation (SaO2). Regression analysis results indicated that the TAC levels remained significantly and negatively correlated with mean SaO2 levels. Moreover, the CRP levels remained significantly correlated with the apnea-hypopnea index and DI after controlling for covariates.. The present study demonstrated that a preferentially adaptive antioxidative response to hypoxia emerges, and the role of OSA with respect to inflammatory reaction is attenuated, in ischemic stroke patients with OSA.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aged; Biomarkers; Brain Ischemia; C-Reactive Protein; Cross-Sectional Studies; Deoxyguanosine; Female; Humans; Inflammation; Interleukin-6; Male; Middle Aged; Oxidative Stress; Polysomnography; Prospective Studies; Recurrence; Risk Factors; Severity of Illness Index; Sleep Apnea, Obstructive; Stroke

Oxidative and nitrosative stress has suggested to be involved in the pathophysiology of cardiovascular diseases, but has unclear relationship with the risk for incident stroke.. In this nested case-control study, cases consisted of 131 participants who were free of stroke at screening and experienced incident stroke during the follow-up period. Controls were 1:1 frequency-matched for age and sex. Baseline levels of urinary creatinine-indexed biomarkers were measured using liquid chromatography-tandem mass spectrometry, including 8-iso-prostaglandin F₂α (8-iso-PGF₂α), 4-hydroxynonenal conjugate with mercapturic acid, 8-hydroxydeoxyguanosine and 8-nitroguanine.. The levels of urinary 8-iso-PGF₂α in stroke cases were higher than in controls [median (interquartile range), 1.13 (2.23-4.36) μg/g creatinine versus 0.71 (1.34-3.02) μg/g creatinine, p=0.004]. After adjusting cardiovascular risk factors, the association remained that higher level of urinary 8-iso-PGF₂α entailed the greater risk for incident stroke [per 1 standard deviation increase in log-transformed value, adjusted odds ratio, 1.40; 95% confidence interval (CI), 1.06-1.85; p=0.005] with a significant increasing trend across its quartiles (p for trend=0.016). After adding urinary 8-iso-PGF₂α, the prediction model not only improved discrimination between participants with or without incident stroke (integrated discrimination improvement, 0.025; 95% CI, 0.006-0.045; p=0.005), but enhanced stroke risk stratification (net reclassification improvement, 19.8%; 95% CI, 4.6-35.1%; p=0.011). In contrast, the relationships were non-significant among the other three biomarkers.. Our findings demonstrated that urinary 8-iso-PGF₂α could be an independent biomarker of oxidative stress for prediction of the risk for incident stroke.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aged; Aldehydes; Biomarkers; Blood Pressure; Body Mass Index; Cardiovascular Diseases; Case-Control Studies; Chromatography; Creatinine; Deoxyguanosine; Dinoprost; Female; Guanine; Humans; Male; Middle Aged; Oxidative Stress; Predictive Value of Tests; Prospective Studies; Risk Factors; Stroke; Tandem Mass Spectrometry

We evaluated the reliability of 8-hydroxy-2'-deoxyguanosine (8-OHdG), and determined its ability to predict functional outcomes in stroke survivors. The rehabilitation effect on 8-OHdG and functional outcomes were also assessed. Sixty-one stroke patients received a 4-week rehabilitation. Urinary 8-OHdG levels were determined by liquid chromatography-tandem mass spectrometry. The test-retest reliability of 8-OHdG was good (interclass correlation coefficient=0.76). Upper-limb motor function and muscle power determined by the Fugl-Meyer Assessment (FMA) and Medical Research Council (MRC) scales before rehabilitation showed significant negative correlation with 8-OHdG (r=-0.38, r=-0.30; p<0.05). After rehabilitation, we found a fair and significant correlation between 8-OHdG and FMA (r=-0.34) and 8-OHdG and pain (r=0.26, p<0.05). Baseline 8-OHdG was significantly correlated with post-treatment FMA, MRC, and pain scores (r=-0.34, -0.31, and 0.25; p<0.05), indicating its ability to predict functional outcomes. 8-OHdG levels were significantly decreased, and functional outcomes were improved after rehabilitation. The exploratory study findings conclude that 8-OHdG is a reliable and promising biomarker of oxidative stress and could be a valid predictor of functional outcomes in patients. Monitoring of behavioral indicators along with biomarkers may have crucial benefits in translational stroke research.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Aged; Biomarkers; Chromatography, High Pressure Liquid; Deoxyguanosine; DNA Damage; Fatigue; Female; Humans; Male; Middle Aged; Motor Activity; Oxidative Stress; Pain Management; Stroke; Stroke Rehabilitation

To elucidate the pathogenic roles of oxidative stress on blood-brain-barrier (BBB) dysfunction, we compared the chronological changes of oxidative stress in blood and cerebral tissue between stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive Wistar-Kyoto rats (WKY). Plasma and tissue oxidative stress was assayed by the diacron-reactive oxygen metabolite (d-ROM) test using 8-hydroxy-2'-deoxyguanosine (8-OHdG) as a reference oxidative stress marker. The plasma and cerebral cortex d-ROM levels increased in SHRSP after 16weeks of age, but not in WKY. There were no significant differences in 8-OHdG or lipid peroxidation markers between SHRSP and WKY. Antioxidant capacity, as estimated by the biological antioxidant potential test, was similar between SHRSP and WKY at all ages examined. The changes in plasma and tissue d-ROM levels coincided with changes in glucose transporter-1 and aquaporin-4 expression, as functional constituents of the BBB. These results indicate that plasma oxidative stress increases before the onset of tissue damage, and plays an important role in BBB dysfunction rather than decreases in antioxidant capacity. The plasma d-ROM test appears to be useful for predicting vasogenic cerebral edema in severe hypertension.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Aquaporin 4; Biomarkers; Blood Pressure; Blood-Brain Barrier; Body Weight; Brain Edema; Capillary Permeability; Deoxyguanosine; Disease Models, Animal; Glucose Transporter Type 1; Hypertension; Lipid Peroxidation; Male; Oxidative Stress; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Stroke; Time Factors

This study examined the effects of continual Gram-negative bacterial challenge on stroke onset. Stroke onset occurred significantly earlier in stroke-prone spontaneously hypertensive rats (SHRSP) injected with a bacterial cell suspension of Gram-negative rods or lipopolysaccharides (LPSs) than in uninjected controls. Paralysis of the hindlimb, piloerection, hypokinesis, and hyperkinesis were observed in LPS-injected SHRSP but not in uninjected controls during stroke onset. The serum levels of NOx, thiobarbituric acid reactive substance, and 8-hydroxydeoxyguanosine increased in LPS-injected SHRSP. These results suggest that continual Gram-negative bacterial challenge induces accelerated stroke onset in SHRSP, probably caused by oxidative stress responses derived from LPSs.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Age Factors; Animals; Biomarkers; Blood Pressure; Brain; Deoxyguanosine; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Hypertension; Lipopolysaccharides; Nitrogen Oxides; Rats; Rats, Inbred SHR; Stroke; Thiobarbituric Acid Reactive Substances

It is known that vitamin E and some carotenoids have antioxidant activities that alleviate endothelial dysfunction and play a protective role against cardiovascular disease. The current study was designed to examine the hypothesis that astaxanthin, a red pigment carotenoid found in salmonid and crustacean aquaculture, protects stroke-prone spontaneously hypertensive rats (SHRSP) from vascular oxidative damage, hypertension, and cerebral thrombosis. Male 6-week-old SHRSP were classified into 4 groups: a control group, 2 astaxanthin groups, and a vitamin E group. The treated animals were given either astaxanthin or vitamin E for 3 weeks. Body weights in each group were not significantly different from control group during the treatment period, but the usual increase in systolic blood pressure in SHRSP observed with age was significantly suppressed by treatment. Thrombogenesis, assessed using a helium-neon (He-Ne) laser technique in pial blood vessels, together with antioxidant activity, assessed by measuring urinary 8-OHdG levels, were significantly moderated. Urinary nitric oxide (NO) metabolites were increased after treatment. These results supported our hypothesis and strongly suggested that the antithrombotic and antihypertensive effects of astaxanthin or vitamin E may be related to an increase in bioavailable NO, possibly mediated by decreased inactivation of NO by reactive oxygen species.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Antihypertensive Agents; Antioxidants; Cardiovascular Diseases; Deoxyguanosine; Dose-Response Relationship, Drug; Fibrinolytic Agents; Hypertension; Intracranial Thrombosis; Male; Nitrates; Nitric Oxide; Nitrites; Oxidative Stress; Rats; Rats, Inbred SHR; Risk Factors; Specific Pathogen-Free Organisms; Stroke; Xanthophylls

We have demonstrated previously that both acute and chronic oral administration of adenosine have novel functions such as anti-hypertensive effects and improved hyperlipidaemia in stroke-prone spontaneously hypertensive rats (SHRSP) fed a normal diet. The purpose of the present study was to investigate the effect of adenosine administration on metabolic syndrome-related parameters in SHRSP fed a high-fat diet. Six-week-old rats were divided into three groups, and were administered either water (control) or adenosine (10 or 100 mg/l) for 8 weeks. During this period, the rats had free access to a high-fat diet based on AIN-93M. The results showed that hypertension, plasma lipid, NO, insulin, glucose and urinary 8-hydroxy-2'-deoxyguanosine levels improved significantly in both adenosine groups. The mRNA expression levels of genes involved in anti-oxidative activity and adenosine receptors were also altered in the adenosine groups. Administration of adenosine also increased plasma adiponectin levels, accompanied by upregulation of mRNA expression level of adiponectin and adiponectin receptor 1 in perirenal fat and adiponectin receptor 2 in the liver. In conclusion, oral administration of adenosine is effective for improving metabolic syndrome-related parameters in SHRSP, and accordingly it may prevent the progression of the metabolic syndrome.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adenosine; Adiponectin; Adipose Tissue; Animals; Antioxidants; Blood Glucose; Cardiovascular Agents; Deoxyguanosine; Dietary Fats; Enzymes; Gene Expression; Gene Expression Regulation; Hypertension; Insulin; Kidney; Lipids; Liver; Male; Metabolic Syndrome; Nitric Oxide; Rats; Rats, Inbred SHR; Receptors, Adiponectin; RNA, Messenger; Stroke

Intake of n-3 polyunsaturated fatty acids such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) has been suggested to associate with an increased risk of hemorrhagic stroke. The present study was designed to investigate the hypothesis that EPA and DHA increase oxidative stress and hemorrhage volume in rats with intracerebral hemorrhagic (ICH) stroke. Thirty-five-week-old male rats were fed an American Institute of Nutrition-93M diet containing 0% (n = 27), 0.5% (n = 15), or 1% EPA + DHA of total energy for 5 weeks. Of 5 rats fed 1% EPA + DHA (41%), 5 died because of excessive bleeding within 12 hours after ICH surgery. Behavior test score and hemorrhage volume were significantly (P < .05) greater in the 1% EPA + DHA-fed rats than in other rats. Magnetic resonance imaging consistently showed that edema and bleeding were visible in only the rats fed 1% EPA + DHA. Levels of superoxide dismutase and glutathione were significantly (P < .05) lower in rats fed 0.5% and 1% EPA + DHA than those fed 0% EPA + DHA. Thiobarbituric acid-reactive substance content was significantly (P < .05) higher in 1% EPA + DHA-fed rats than in 0% and 0.5% EPA + DHA-fed rats. The level of 8-hydroxydeoxyguanosine was significantly (P < .05) higher in ICH rats with all diets than in sham surgery rats. Brain levels of EPA and DHA were highest in rats fed 1% EPA + DHA than in rats fed 0% and 0.5% EPA + DHA. These results suggested that intake of 1% EPA + DHA of total energy could lead to oxidative damage to the brain and thus increase the risk of intracerebral hemorrhagic stroke in this rat model.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Behavior, Animal; Brain; Deoxyguanosine; Dietary Fats; Docosahexaenoic Acids; Edema; Eicosapentaenoic Acid; Glutathione; Hemorrhage; Intracranial Hemorrhages; Magnetic Resonance Imaging; Male; Oxidative Stress; Rats; Rats, Sprague-Dawley; Stroke; Superoxide Dismutase; Thiobarbituric Acid Reactive Substances

The aim of this study is to investigate the effects of dietary supplementation with the Driselase-treated fraction (DF) of rice bran and ferulic acid (FA) on hypertension and glucose and lipid metabolism in stroke-prone spontaneously hypertensive rats (SHRSP). Male SHRSP at 4 weeks of age were divided into three groups, and for 8 weeks were fed (1) a control diet based on AIN-93M, (2) a DF of rice bran-supplemented diet at 60 g/kg and (3) an FA-supplemented diet at 0.01 g/kg. Means and standard errors were calculated and the data were tested by one-way ANOVA followed by a least significance difference test. The results showed that both the DF and FA diets significantly improved hypertension as well as glucose tolerance, plasma nitric oxide (NOx), urinary 8-hydroxy-2'-deoxyguanosine and other parameters. In particular, compared to the FA diet, the DF diet produced a significant improvement in urinary NOx, hepatic triacylglycerol and several mRNA expressions of metabolic parameters involved in glucose and lipid metabolisms. The results of the metabolic syndrome-related parameters obtained from this study suggest that the DF diet is more effective than the FA diet.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Antihypertensive Agents; Biomarkers; Blood Glucose; Coumaric Acids; Deoxyguanosine; Dietary Fiber; Fungal Proteins; Glucose Tolerance Test; Glycoside Hydrolases; Hypertension; Kidney; Lipid Metabolism; Liver; Male; Nitric Oxide; Oryza; Peptidyl-Dipeptidase A; Rats; Rats, Inbred SHR; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Stroke

Effect of dietary supplementation of two types of rice bran fraction on blood pressure (BP), lipid profile, and glucose metabolism in stroke-prone spontaneously hypertensive rats was studied. Male 4-week-old rats were divided into one group fed the AIN-93M-based control (C) diet and two groups fed diet supplemented with 60 g/kg of Driselase and ethanol fractions (DF and EF, respectively) of rice bran. After 8 weeks feeding, the BP decreased in the DF and EF groups in comparison with the C group (p < 0.01). Plasma ACE inhibitory activity, BUN, BUN/creatinine ratio, albumin, triglyceride, and glucose levels were lower in the DF and EF groups than in the C group (p < 0.01). Plasma nitric oxide and urinary 8-hydroxy-2'-deoxyguanosine levels were lower in the DF and EF groups than in the C group (p < 0.01). Rice bran fractions appear to have a beneficial dietary component that improves hypertension, hyperlipidemia, and hyperglycemia.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Blood Glucose; Blood Pressure; Catechin; Deoxyguanosine; Diet; Ethanol; Fungal Proteins; Gallic Acid; Glycoside Hydrolases; Hypertension; Lipids; Male; Nitric Oxide; Oryza; Rats; Rats, Inbred SHR; Stroke

The preventive effects of sesamin, a lignan from sesame oil and vitamin E on hypertension and thrombosis were examined using stroke-prone spontaneously hypertensive rats (SHRSP). Animals at 5 weeks of age were separated into four groups: (i) control group; (ii) vitamin E group, which was given 1000 mg alpha-tocopherol/kg diet; (iii) sesamin group, given 1000 mg sesamin/kg diet; and (iv) vitamin E plus sesamin group, given 1000 mg alpha-tocopherol plus 1000 mg sesamin/kg diet for 5 weeks from 5 to 10 weeks of age. Resting blood pressure was measured by the tail-cuff method once weekly. A closed cranial window was created in the right parietal bone of the rat and platelet-rich thrombi were induced in vivo using a helium-neon laser technique. The number of laser pulses required for formation of an occlusive thrombus was used as an index of thrombotic tendency. In control rats, systolic blood pressure and the amount of urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) became significantly elevated with age. However, the elevation in blood pressure and 8-OHdG were significantly suppressed in rats administered vitamin E, sesamin, or vitamin E plus sesamin. At 10 weeks, the number of laser pulses required to induce an occlusive thrombus in arterioles of the control group was significantly lower than in the other groups (P < 0.05). These results indicate that chronic ingestion of vitamin E and sesamin attenuated both elevation in blood pressure, oxidative stress and thrombotic tendency, suggesting that these treatments might be beneficial in the prevention of hypertension and stroke.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Antihypertensive Agents; Antioxidants; Blood Pressure; Deoxyguanosine; Dioxoles; Fibrinolytic Agents; Hypertension; Intracranial Thrombosis; Lignans; Rats; Rats, Inbred SHR; Stroke; Vitamin E

Stroke produces a region of complete cell death and areas of partial damage, injury, and gliosis. The spatial relationship of these regions of damage to the infarct core and within spared neuronal circuits has not been identified. A model of cortical stroke was developed within functional subsets of the somatosensory cortex. Infarct size, regions of apoptosis, oxidative DNA damage, heat shock protein induction, and subtypes of reactive gliosis were precisely mapped with the somatosensory body map, quantified, and interrelated. Three tissue microenvironments were recognized: zones of partial ischemic damage, heat shock protein induction, and distributed gliosis. These three zones involved progressively more distant cortical regions, each larger than the infarct core. The zone of partial ischemic damage represents an overlap region of apoptotic cell death, oxidative DNA damage, loss of synaptic connections, and local reactive gliosis. The zone of distributed gliosis occupies distinct functional areas of the somatosensory cortex. The tissue reorganization induced by stroke is much larger than the stroke site itself. Adjacent tissue microenvironments are sites of distinct reactive cellular signaling and may serve as a link between the processes of acute cell death and delayed neuronal plasticity after focal stroke.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Apoptosis; Caspase 3; Caspases; Deoxyguanosine; HSP70 Heat-Shock Proteins; In Situ Nick-End Labeling; Intermediate Filament Proteins; Male; Models, Neurological; Nerve Tissue Proteins; Nestin; Rats; Rats, Sprague-Dawley; Somatosensory Cortex; Stroke; Vimentin

The preventive effects of sesamin, a lignan from sesame oil, and vitamin E on hypertension and thrombosis were examined using stroke-prone spontaneously hypertensive rats (SHRSP). At 5 weeks of age the animals were separated into four groups: (i) a control group; (ii) a vitamin E group, which was given a 1,000 mg alpha-tocopherol/kg diet; (iii) a sesamin group, given a 1,000 mg sesamin/kg diet; and (iv) a vitamin E plus sesamin group, given a 1,000 mg alpha-tocopherol plus 1,000 mg sesamin/kg diet for 5 weeks from 5 to 10 weeks of age. Resting blood pressure was measured by the tail-cuff method once weekly. A closed cranial window was created and platelet-rich thrombi were induced in vivo using a helium-neon laser technique. The number of laser pulses required for formation of an occlusive thrombus was used as an index of thrombotic tendency. In control rats, systolic blood pressure and the amount of urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) became significantly elevated with age. However, the elevation in blood pressure and 8-OHdG were significantly suppressed in rats administrated vitamin E, sesamin, or vitamin E plus sesamin. At 10 weeks, the number of laser pulses required to induce an occlusive thrombus in arterioles of the control group was significantly lower than in the other groups (p<0.05). These results indicate that chronic ingestion of vitamin E and sesamin attenuated each of elevation in blood pressure, oxidative stress and thrombotic tendency, suggesting that these treatments might be beneficial in the prevention of hypertension and stroke.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Blood Pressure; Blood Vessels; Body Weight; Cerebrovascular Circulation; Cerebrovascular Disorders; Deoxyguanosine; Dioxoles; Disease Susceptibility; Drug Combinations; Genetic Predisposition to Disease; Hypertension; Lignans; Male; Microcirculation; Rats; Rats, Inbred SHR; Stroke; Thrombosis; Vasomotor System; Vitamin E