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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of the present study is to evaluate the effect of eicosapentaenoic acid (EPA), dl-alpha-lipoic acid (LA) and eicosapentaenoate-lipoate (EPA-LA) derivative on the atherogenic disturbances in hypercholesterolemic atherogenic animals. Eight groups of male Wistar rats were employed in this study, wherein four groups were fed with a high cholesterol diet (rat chow supplemented with 4% cholesterol and 1% cholic acid; HCD) for 30 days, among which, three groups of rats were also treated with either EPA (35 mg/kg body weight/day, oral gavage), LA (20 mg/kg body weight/day, oral gavage) or EPA-LA derivative (50 mg/kg body weight/day, oral gavage) commencing from 16th day of the experimental period. The remaining four groups served as control and EPA, LA and EPA-LA derivative treated drug controls. Abnormal increases in the levels of malondialdehyde, protein carbonyl and 8-hydroxy-2-deoxyguanosine, as well as depressed antioxidants status, were observed in hepatic tissue of HCD fed rats. HCD induced abnormal elevation in the activities of hepatic lactate dehydrogenase, aminotransferases and alkaline phosphatase (ALP) and was accompanied by increased hepatic cholesterol level and altered fatty changes in the histology of liver. These changes were restored partially in the EPA and LA administered groups. However, the combined derivative EPA-LA almost ameliorated the hypercholesterolemic-oxidative changes in the HCD fed rats. The results of this study present oxidative injury induced by hypercholesterolemic diet and administration of the combination treatment of EPA-LA afforded sound protection against lipemic-oxidative injury.
Atherosclerosis 2006 Nov
PMID:Protective role of eicosapentaenoate-lipoate (EPA-LA) derivative in combating oxidative hepatocellular injury in hypercholesterolemic atherogenesis. 1645 14

Metabolic syndrome is a cluster of metabolic diseases that in essence greatly promotes progression of atherosclerosis. We used a genetic model of the metabolic syndrome, the SHR/NDmcr-cp (SHR/cp) rat, from 6 to 40 weeks of age to investigate whether systemic oxidative stress, a major cause of atherosclerosis, increases in this syndrome. Nine-week-old male rats already showed manifestations of metabolic syndrome, including heavier body weight, higher blood pressure and higher levels of serum glucose, insulin and various lipids compared to the age-matched Wistar Kyoto (WKY) rats used as a genetic control. These metabolic parameters gradually progressed with age. Likewise, the serum levels of oxidative stress markers, including lipid peroxides, which oxidatively modify low-density lipoprotein (LDL) and 8-hydroxydeoxyguanosine (8-OHdG), gradually increased in SHR/cp rats. The serum levels of 3-nitrotyrosine and 3-chlorotyrosine also persistently increased, indicating the involvement of peroxynitrite or myeloperoxidase-catalyzed oxidation. In addition, high-sensitivity C-reactive protein (hsCRP), an early marker of inflammation, temporarily increased in SHR/cp rats compared to WKY rats. These findings suggest that oxidative stress, as well as nitrative stress and inflammation, increases in the metabolic syndrome, which may contribute to the development of atherosclerosis.
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PMID:Elevated circulating levels of markers of oxidative-nitrative stress and inflammation in a genetic rat model of metabolic syndrome. 1679 31

Corosolic acid (CRA), a constituent of banaba leaves, has been reported to have anti-inflammatory and hypoglycemic activities. The aim of this study was to determine the effects of CRA on metabolic risk factors including obesity, hypertension, hyperinsulinemia, hyperglycemia, and hyperlipidemia together with oxidative stress and inflammation, all of which are characteristic of the SHR/NDmcr-cp (cp/cp) (SHR-cp) rat, an animal model of metabolic syndrome. Six-week-old male SHR-cp rats were fed a high fat diet containing 0.072% CRA for 14 weeks. Treatment with CRA lowered blood pressure, which was elevated in control animals, by 10% after 8 weeks, and serum free fatty acids by 21% after 2 weeks. CRA treatment resulted in decreases in the levels of the oxidative stress markers thiobarbituric acid-reactive substances and 8-hydroxydeoxyguanosine by 27% and 59%, respectively, after 2 weeks. CRA treatment also reduced the levels of myeloperoxidase markers, 3-nitrotyrosine and 3-chlorotyrosine by 38% and 39%, respectively, after 10 weeks, and tended to decrease the levels of high sensitivity C-reactive protein, a marker of inflammation, after 6 weeks. However, CRA had no effect on weight gain or hyperglycemia. These results demonstrate that CRA can ameliorate hypertension, abnormal lipid metabolism, and oxidative stress as well as the inflammatory state in SHR-cp rats. This implies that CRA can be beneficial for preventing atherosclerosis-related diseases that are an increasing health care problem worldwide.
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PMID:Corosolic acid prevents oxidative stress, inflammation and hypertension in SHR/NDmcr-cp rats, a model of metabolic syndrome. 1695 74

Oxidative stress is at play in the progression of chronic renal failure (CRF) and in the genesis of atherosclerosis. The aim of the present study was to evaluate the factors that might influence the oxidative-antioxidative balance in patients on hemodialysis. The study group consisted of 71 hemodialysis patients due to CRF. Sixteen healthy subjects constituted a control group. The levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG), C-reactive protein (CRP), and the blood lipid profile were measured in both groups. The results showed significantly higher mean levels of both 8-OHdG and CRP in the hemodialysis patients compared with that in the control subjects. The highest level of 8-OHdG was found in the subgroups of the patients with CRF primarily caused by diabetes (16.4 ng/ml) and with hypertensive nephropathy (15.8 ng/ml). More than a 2.5-fold higher level of 8-OHdG in the hemodialysis patients compared with the control subjects points to the presence of intensive oxidative stress in the patients.
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PMID:What influences the level of oxidative stress as measured by 8-hydroxy-2'-deoxyguanosine in patients on hemodialysis? 1707 47

Arterial dysfunction is a hallmark of early atherosclerosis; however, its behavior in patients with metabolic syndrome (MS) is still unclear. We investigated the role of oxidative stress on ischemia-induced flow-mediated dilatation (FMD) in patients with MS. FMD and oxidative stress, as assessed by serum levels of 8-hydroxy-2-deoxy-2-deoxyguanosine (8-OHdG), were studied in 18 MS and 30 control subjects. Thereafter, in the 18 MS patients, FMD was assessed after iv infusion of 1 g vitamin C or placebo in a randomized, double-blind, crossover design; serial blood samples were taken in peripheral circulation before and after FMD to analyze 8-OHdG. Compared to controls, MS patients had higher 8-OHdG (p<0.001) and lower FMD (p<0.001); 8-OHdG and FMD were inversely correlated (R=-0.74; p<0.01). In MS patients, placebo administration did not change FMD, whereas vitamin C significantly enhanced it (p<0.001). After placebo, ischemia-induced FMD was associated with a significant increase in 8-OHdG (p<0.001), an effect that was counteracted by vitamin C. Vitamin C infusion was associated with an inverse correlation between the changes in FMD and oxidative stress (R=-0.67; p<0.01). The present study shows that arterial dilatation is impaired and that enhanced oxidative stress may play a key role in patients with MS.
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PMID:Oxidative stress-mediated arterial dysfunction in patients with metabolic syndrome: Effect of ascorbic acid. 1766 49

Individuals with insulin resistance and diabetes mellitus have increased cardiovascular morbidity and mortality, caused in part by vascular complications. Endothelial dysfunction has been implicated in the pathogenesis of vascular diabetic disease. This abnormal function of the vasculature precedes cardiovascular disease and is associated with impaired endothelium-dependent vasorelaxation. The main etiology of the increased mortality and morbidity of type 2 diabetic patients is atherosclerosis. Increased production of free radicals is associated with the pathophysiology of diabetes, resulting in oxidative damage to lipids and proteins. Reduction of oxidative stress in diabetic patients may delay the onset of atherogenesis and the appearance of micro- and macrovascular complications. Alpha-lipoic acid (LA) is a multifunctional antioxidant that has been shown to have beneficial effects on polyneuropathy and on markers of oxidative stress in various tissues. This study was conducted to investigate the effects of LA on endothelial function in diabetic and hyperlipidemic animal models. Carbohydrate and lipid metabolism, endothelial function, plasma malondialdehyde (MDA) and urinary 8-hydroxydeoxyguanosine (8-OHdG) were assessed in non-diabetic controls (Wistar rats), untreated diabetic Goto-Kakizaki (GK) rats and, atherogenic diet (AD)-fed GK rats (fed with atherogenic diet only, treated with alpha-lipoic acid and treated with vehicle, for 3 months). AD resulted in a 3-fold increase in both total and non-HDL serum cholesterol levels and in a 2-fold increase triglyceride levels while endothelial function was significantly reduce MDA and 8-OHdG levels were higher in the GK and GK hyperlipidemic groups and were completely reversed by the antioxidant. Hyperlipidemic GK diabetic rats showed significantly reduced endothelial function that was partially improved with LA. Furthermore, lipoic acid significantly reduced serum cholesterol levels, without lowering HDL cholesterol. Alpha-lipoic acid supplementation represents an achievable adjunct therapy to improve endothelial function and reduce oxidative stress, factors that are implicated in the pathogenesis of atherosclerosis in diabetes.
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PMID:Endothelial dysfunction in type 2 diabetes: effect of antioxidants. 1784 45

Exposure to a large number of environmental toxins can induce damage to DNA and may play an important role in the pathophysiological processes of atherosclerosis. To examine the effect of some specific environmental conditions that predispose to sudden coronary atherosclerotic death on the level of 8-OHdG, urine samples were collected from cases of certain occupations and polluted regions that showed a high prevalence of premature deaths. The samples were then analyzed for 8-OHdG. Analysis of 108 cases and 45 controls showed a significant high level of 8-OHdG in relation to occupations, habits, residency and work shift. The mean +/- standard deviation (M +/- SD) for the control group was 4.5 +/- 2.3 ng 8-OHdG/mg creatinine (n = 45), compared to 9.1 +/- 3.1 ng/mg in taxi drivers (n = 9), 10 +/- 5.5 ng/mg in chemical factory workers (n = 16), 12.0 +/- 8.9 ng/mg in paint workers (n = 9), 14.6 +/- 11.1 ng/mg in gasoline station workers (n = 15), 15 +/- 6.1 ng/mg in cement factory workers (n = 12), 16.4 +/- 3.2 ng/mg in city center inhabitants (n = 18) and 18.6 +/- 3.2 ng/mg in smokers (n = 15). These conditions at least in the pilot study done by the author, showed some form of precipitation of sudden atherosclerotic coronary death. This work proved that the recently used 8-OHdG DNA damage biomarker may be an important marker of environmental conditions that are expected to have a serious long-term impact on the cardiovascular system.
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PMID:8-Hydroxy-2'-deoxyguanosine (8-OHdG) as a short-term predictor of regional and occupational health problems. 1790 4

Hemodialyzed patients with chronic kidney disease are prone to atherosclerosis, which occurs due mainly to lipid abnormalities. Abnormal lipid metabolism could result, among others, from increased formation of free radicals and, consequently, oxidative stress in these patients. The objective of the present study was to evaluate the influence of therapy with lovastatin or with a hypolipemic diet only on oxidative stress in hemodialyzed patients. We addressed the issue by measuring the total antioxidant status (TAS) and the level of 8-hydroxy-2-deoxyguanosine (8-OHdG), an oxidative DNA damage metabolite, in the serum. The study group consisted of 71 patients. They were divided into 3 groups: treated with lovastatin (20 mg/day, n=30), with a hypolipemic diet alone (n=28), and untreated controls (n=13). Serum levels of TAS and 8-OHdG (8-hydroxy-2-deoxyguanosine) were determined. Blood samples were collected at the beginning of the study and then after a 6 months' therapy. We found that the level of 8-OHdG decreased considerably only in the lovastatin-treated group; the decrease was from 15.6+/-8.1 to 12.5+/-4.8 ng/ml (P=0.04). In the other two groups changes in 8-OHdG were insignificant. The level of TAS increased significantly in the lovastatin-treated group from 1.28+/-0.20 to 1.37+/-0.116 mmol/l (P=0.011), decreased in the diet-treated group from 1.55+/-0.14 to 1.45+/-0.11 mmol/l (P=0.007), and remained unchanged in the untreated group (1.42+/-0.11 vs. 1.40+/-0.12 mmol/l). We conclude that lovastatin, but not a hypolipemic diet alone, exerts an antioxidant effect in hemodialyzed patients. However, the determinants of the antioxidant effect of statins in patients with chronic renal failure are unclear and their resolution would require alternative study designs.
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PMID:Comparison of a statin vs. hypolipemic diet on the oxidant status in hemodialyzed patients with chronic renal failure. 1820 48

Synthesis of nitric oxide (NO) can be blocked by inhibition of nitric oxide synthase (NOS) active site with guanidino-substituted analogues of l-arginine such as asymmetric dimethylarginine (ADMA). There is growing evidence that elevation of serum ADMA levels play a role in the progression of atherosclerosis and chronic kidney disease (CKD) in high-risk patients. Further, dyslipidemia contributes to cardiorenal disease as well. However, effects of ezetimibe, a specific inhibitor of cholesterol absorption and widely used drug for the treatment of dyslipidemia, on serum ADMA levels and renal injury remain unknown. In this study, we examined whether ezetimibe treatment decreased serum levels of ADMA, proteinuria and urinary excretion levels of 8-hydroxydeoxyguanosine (8-OHdG) and l-fatty acid binding protein (l-FABP), markers of oxidative stress and tubular injury, respectively and investigated their relationships in 10 non-diabetic CKD patients with dyslipidemia. Ezetimibe treatment (10mg/day) for 6 months significantly decreased circulating levels of LDL-cholesterol, triglycerides and ADMA, while it increased HDL-cholesterol levels. Further, ezetimibe treatment significantly reduced urinary excretion levels of protein, l-FABP and 8-OHdG. In univariate analyses, serum ADMA levels were correlated with urinary protein, l-FABP and 8-OHdG levels. In multiple stepwise regression analysis, proteinuria was independently correlated with ADMA. Our present study demonstrated for the first time that ezetimibe decreased serum ADMA levels and improved renal injury in non-diabetic CKD patients with dyslipidemia in a cholesterol-independent manner. Ezetimibe may have pleiotropic actions, that is, ADMA-lowering and anti-oxidative effects, that could contribute to renoprotective properties of this lipid-lowering agent.
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PMID:Ezetimibe decreases serum levels of asymmetric dimethylarginine (ADMA) and ameliorates renal injury in non-diabetic chronic kidney disease patients in a cholesterol-independent manner. 1940 91

Various oxidative stress markers have been measured to evaluate the status of heart failure (HF). However, the relationships between these markers and the aetiology of HF have not been fully investigated. This study compared 8-hydroxy-2'-deoxyguanosine (8-OHdG) and biopyrrins levels in patients with ischemic and non-ischemic HF. Study subjects were divided into a coronary artery disease (CAD) group (n=70), a non-CAD group (n=61) and a control group (n=33). In the CAD group, 8-OHdG and biopyrrins levels increased with the severity of the New York Heart Association (NYHA) functional class and log BNP levels correlated with 8-OHdG and biopyrrins levels. However, non-CAD patients with NYHA class III/IV had significantly lower 8-OHdG levels than CAD patients with NYHA class III/IV and the levels did not correlate with log BNP levels. In the CAD group, 8-OHdG levels reflected the severity of atherosclerosis. These results indicate that the properties of oxidative stress markers should be carefully taken into consideration for the assessment of HF status.
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PMID:Differences in oxidative stress markers based on the aetiology of heart failure: comparison of oxidative stress in patients with and without coronary artery disease. 1990 78


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