Lipid peroxidation and neurodegenerative disease

Lipid peroxidation is a complex process involving the interaction of oxygen-derived free radicals with polyunsaturated fatty acids, resulting in a variety of highly reactive electrophilic aldehydes. Since 1975, lipid peroxidation has been extensively studied in a variety of organisms. As neurodegenerative diseases became better understood, research establishing a link between this form of oxidative damage, neurodegeneration, and disease has provided a wealth of knowledge to the scientific community. With the advent of proteomics in 1995, the identification of biomarkers for neurodegenerative disorders became of paramount importance to better understand disease pathogenesis and develop potential therapeutic strategies. This review focuses on the relationship between lipid peroxidation and neurodegenerative diseases. It also demonstrates how findings in current research support the common themes of altered energy metabolism and mitochondrial dysfunction in neurodegenerative disorders.     

Lipid peroxidation in aging brain and Alzheimer's disease

Lipid peroxidation is one of the major outcomes of free radical-mediated injury that directly damages membranes and generates a number of secondary products, both from fission and endocyclization of oxygenated fatty acids that possess neurotoxic activity. Numerous studies have demonstrated increased lipid peroxidation in brain of patients with Alzheimer's disease (AD) compared with age-matched controls. These data include quantification of fission and endocyclized products such as 4-hydroxy-2-nonenal, acrolein, isoprostanes, and neuroprostanes. Immunohistochemical and biochemical studies have localized the majority of lipid peroxidation products to neurons. A few studies have consistently demonstrated increased cerebrospinal fluid (CSF) levels of isoprostanes in AD patients early in the course of their dementia, and one study has suggested that CSF isoprostanes may improve the laboratory diagnostic accuracy for AD. Similar analyses of control individuals over a wide range of ages indicate that brain lipid peroxidation is not a significant feature of usual aging. Quantification of isoprostanes in plasma and urine of AD patients has yielded inconsistent results. These results indicate that brain lipid peroxidation is a potential therapeutic target in probable AD patients, and that CSF isoprostanes may aid in the assessment of antioxidant experimental therapeutics and the laboratory diagnosis of AD.     

Lipid peroxidation markers in children with anxiety disorders and their diagnostic implications

Abstract

Objective

Numerous factors, including genetic, neurobiological, neurochemical, and psychological factors, are thought to be involved in the development of anxiety disorders. The latest findings show that the pathophysiology of anxiety disorders might be associated with oxidative stress and lipid peroxidation; however, no studies have so far investigated lipid peroxidation markers in children with anxiety disorders. Serum levels of lipid hydroperoxide (LOOH) are a reliable marker of lipid peroxidation. Paraoxonase and arylesterase are two enzymes that protect against such peroxidation, and might also be diagnostic markers. In this study, we investigated whether there are associations between anxiety disorders and lipid peroxidation markers in children, and assessed the diagnostic performance of these markers.

Methods

The study group consisted of 37 patients (children and adolescents) with anxiety disorders. A control group, matched for age and gender, was composed of 36 healthy subjects. Venous blood samples were collected, and LOOH levels and paraoxonase and arylesterase activity were measured.

Results

LOOH levels were significantly higher in the anxiety disorders group than in the control group. There were no significant differences in paraoxonase or arylesterase activities between the patient and the control groups.

Discussion

Lipid peroxidation or oxidative damage might play a role in the aetiopathogenesis of anxiety disorders. LOOH may be a potential biological marker for anxiety disorders in children.     

Tenascin-C as a noninvasive biomarker of coronary artery disease

Molecular Biology Reports - Coronary artery disease (CAD), is the leading cause of mortality and morbidity worldwide. Tenascin-C (TNC) with high expression levels in inflammatory and cardiovascular...     

Lipid peroxidation and nutrition

Levels of conjugated dienes of fatty acids (first peroxidation product) in relation to their substrates and promotors (triacylglycerols, homocysteine, iron) as well as to their inhibitors (essential antioxidative vitamins) were assessed in a vegetarian group (n=24) and compared with subjects on a mixed diet (traditional nutrition, n=24). Positive significant linear correlation between conjugated dienes and triacylglycerols, homocysteine, iron as well as inverse relationship between conjugated dienes and vitamin E, vitamin C, beta-carotene were observed in pooled groups. Lipid peroxidation risk in vegetarians seems to be caused predominantly by hyperhomocysteinemia, whereas in a mixed diet group this was due to a higher supply of substrates or risk iron values. The incidence of only 8 % of risk conjugated diene values in vegetarians in contrast to 42 % in the group with traditional diet indicates that vegetarians have a better antioxidative status as a consequence of regular consumption of protective food.     

Inflammatory markers and coronary heart disease

PURPOSE OF REVIEW: Despite changes in lifestyle and the use of effective pharmacologic interventions to lower cholesterol levels, coronary heart disease remains the major cause of morbidity and mortality in the developed world. Cholesterol screening fails to identify almost 50% of those individuals who will present with acute coronary syndromes. Recent evidence from laboratory and prospective clinical studies demonstrates that atherosclerosis is not simply a disease of lipid deposition, but rather is an inflammatory process with highly specific cellular and molecular responses. The clinical utility of inflammatory markers has been examined in a variety of atherothrombotic diseases. Because C-reactive protein is highly stable in stored frozen samples, and automated and robust analytical systems for its measurement are available, it has become the most widely examined inflammatory marker. RECENT FINDINGS: C-reactive protein has consistently been shown to be a useful prognostic indicator in acute coronary syndromes and is a strong predictor of future coronary events in apparently healthy individuals. In addition, C-reactive protein can identify individuals with normal lipid levels who are at increased risk for future coronary events. Because drugs such as aspirin and statins reduce inflammatory risk, C-reactive protein has the potential to guide the use of these therapies in high-risk individuals for primary prevention. SUMMARY: C-reactive protein may have a role in global risk assessment for primary prevention and in targeting those patients who will benefit from anti-inflammatory therapies. In addition, it may also be a good prognostic indicator in patients with acute coronary syndromes.     

Lipid peroxidation as a possible cause of TCDD toxicity

The target tissues of TCDD, the dysfunctions that result in death in experimental animals, and the ultimate biochemical lesion(s) caused by TCDD are not known despite numerous studies. We have shown by the thiobarbituric acid and conjugated diene methods that TCDD induces hepatic lipid peroxidation in rats. The lipid peroxidation produced by TCDD is both dose and time dependent. A 5-6 fold increase in lipid peroxidation occurs within 6 days following the administration of 40 micrograms TCDD/kg body weight/day for 3 days. Thus, the toxicity of TCDD may be caused in part by free radical-mediated lipid peroxidation that leads to general cell membrane damage which can ultimately produce death in experimental animals at acutely toxic doses.     

A polymorphism in the visfatin gene promoter is related to decreased plasma levels of inflammatory markers in patients with coronary artery disease

Visfatin, a newly identified proinflammatory adipokine, has been linked to coronary artery disease (CAD). The ?1535C>T polymorphism (rs61330082) located in the visfatin gene promoter is reportedly associated with proinflammatory status. However, it is unclear whether this polymorphism correlates with plasma levels of inflammatory markers including visfatin, hs-CRP, IL-6 and TNF-?? in CAD patients. The present study was to investigate the potential association of the ?1535C>T polymorphism with plasma levels of visfatin, IL-6, C reactive protein (hs-CRP) and TNF-?? in patients with CAD. We conducted a hospital based study with 171 CAD patients to examine the association between the ?1535C>T polymorphism and plasma levels of visfatin, hs-CRP, IL-6 and TNF-??. Plasma visfatin levels were markedly different between patients with stable angina pectoris (SAP, 11.91 ± 0.70 ng/l) and those with unstable angina pectoris (UAP, 17.49 ± 0.20 ng/l) or acute myocardial infarction (AMI, 16.63 ± 0.22 ng/l; SAP versus UAP or AMI, P < 0.05). Compared with the CC genotype, variant genotypes CT and TT correlated with significantly lower levels of visfatin, hs-CRP, IL-6 and TNF-?? in the SAP group (P < 0.05), with lower levels of hs-CRP and IL-6 in the UAP group (P < 0.05), and with lower levels of visfatin in the AMI group (P < 0.05) after adjustment for age, gender, smoking, hypertension, diabetes, dyslipidemia and medication. Our results suggest that the ?1535C>T polymorphism is associated with decreased plasma levels of inflammatory markers in CAD patients, reflecting that this polymorphism might provide a useful marker for predicting the development of CAD events.     

Oxidative status and reduced glutathione levels in premature coronary artery disease and coronary artery disease

Identifying patients at risk of developing premature coronary artery disease (PCAD) which occurs at age below 45 years old and constitutes approximately 7–10% of coronary artery disease (CAD) worldwide remains a problem. Oxidative stress has been proposed as a crucial step in the early development of PCAD. This study was conducted to determine the oxidative status of PCAD in comparison to CAD patients. PCAD (<45 years old) and CAD (>60 years old) patients were recruited with age-matched controls (n?=?30, each group). DNA damage score, plasma malondialdehyde (MDA) and protein carbonyl content were measured for oxidative damage markers. Antioxidants such as erythrocyte glutathione (GSH), oxidised glutathione (GSSG), and glutathione peroxidase activity (GPx), superoxide dismutase (SOD) and catalase (CAT) were also determined. DNA damage score and protein carbonyl content were significantly higher in both PCAD and CAD when compared to age-matched controls while MDA level was increased only in PCAD (p<.05). In contrast, GSH, GSH/GSSG ratio, α-tocotrienol isomer, and GPx activity were significantly decreased, but only in PCAD when compared to age-matched controls. The decrease in GSH was associated with PCAD (OR?=?0.569 95%CI [0.375???0.864], p?=?.008) and cut-off values of 6.69?μM with areas under the ROC curves (AUROC) 95%CI: 0.88 [0.80–0.96] (sensitivity of 83.3%; specificity of 80%). However, there were no significant differences in SOD and CAT activities in all groups. A higher level of oxidative stress indicated by elevated MDA levels and low levels of GSH, α-tocotrienol and GPx activity in patients below 45 years old may play a role in the development of PCAD and has potential as biomarkers for PCAD.     

Crucial markers showing the risk of coronary artery disease in obesity: ADMA and neopterin

BackgroundObesity is responsible for high morbidity and mortality, both in developed and developing countries. It is associated with many chronic and metabolic diseases. Asymmetric dimethylarginine (ADMA) has been demonstrated to be a biomarker of endothelial dysfunction in humans and increased ADMA associated with cardiovascular disease (CVD) risk has been reported in many states. Neopterin (NP) produced by monocytes/macrophages in response to stimulation by interferon-gamma (IFN-γ) is emphasized in recent findings. The current study aims to investigate ADMA and NP levels which may assume a role in guiding the early diagnosis of coronary artery disease in obesity.MethodsThis is an original research study in which ADMA and NP levels of 50 patients (25 male/25 female) diagnosed with obesity were compared with those of 30 healthy individuals (15 male/15 female) as control. The high-performance liquid chromatography (HPLC) method was used while determining parameters.ResultsADMA and NP levels in obese individuals were found to be significantly higher than in those enrolled in the control. ADMA values were found to be higher in obese subjects (0.71±0.24 μmol/L) as compared with levels found in healthy subjects (0.58±0.16 μmol/L) (p<0.05). A significant increase of serum neopterin levels was found in obese subjects (8.8±3.5 μmol/L) as compared with controls (4.9±1.69 μmol/L) (p<0.05). Also, there was a strong positive correlation between NP and ADMA values in obese individuals (r=0.954).ConclusionsOur study revealed that obese subjects have higher ADMA and neopterin levels. These results demonstrated that both ADMA and NP levels may be potential risk factors for coronary heart disease in obesity.     

Lipid peroxidation in neurodegeneration: new insights into Alzheimer's disease

Imbalances of oxidative homeostasis and lipid peroxidation have been revealed as important factors involved in neurodegenerative disorders such as Alzheimer's disease. The brains of patients with Alzheimer's disease contain increased levels of lipid-peroxidation products such as 4-hydroxy-2-nonenal or acrolein, and enhanced lipid peroxidation can also be detected in cerebrospinal fluid and plasma from such patients. Recent research revealed that the interplay of transition metals, amyloid-beta peptide and lipid peroxidation might be responsible for increased oxidative stress and cell damage in this disease. In particular, the contrasting roles of amyloid-beta peptide, as a possible transition metal-chelating antioxidant for lipoproteins and a pro-oxidant when aggregated in brain tissue, has been the focus of discussion recently. In this context, lipid peroxidation has to be seen as an important part of the pathophysiological cascade in Alzheimer's disease, and its measurement in body fluids might serve as a therapy control for Alzheimer's disease and other neurodegenerative diseases.     

高脂血症大鼠四氢生物蝶呤治疗后动脉血管过氧化脂质水平及力学性质改变

目的：探讨长期四氢生物蝶呤（BH4）治疗对高脂血症（HL）大鼠血管脂质过氧化水平及血管力学性质的影响。方法：选用8周龄雄性Wistar大鼠54只,随机分为3组（n=18）：对照组、高脂饮食组（HE组）和高脂饮食并腹腔注射BH4组（HL＋BH4组）,于第8、16和24周龄时每组各杀死6只大鼠测定血脂和脂质过氧化终产物丙二醛（MDA）水平,主动脉血管测量零应力状态张开角、压力-直径关系。结果：至B地治疗后的第16和24周龄,血脂无明显变化,但MDA明显降低（P〈0．01）;HL＋BH4组和HL组比较胸主动脉张开角显著减小（P〈0．01）、压力-直径（P-D）关系曲线上移。结论 BH4可以减轻由于长期高脂血症导致的脂质过氧化,恢复血管弹性,降低血管的结构异常改变。     

Inflammation markers and coronary heart disease.

Evidence supports the position that the chronic atherothrombotic process is intimately associated with what has classically been called 'inflammation'. Proteins that are part of the acute phase response (e.g. fibrinogen, C-reactive protein) are sensitive markers of low-level inflammation, and in population studies, inflammation marker levels at the upper end of the healthy reference range are associated with the presence of subclinical atherothrombotic disease (e.g. carotid wall thickness) and, prospectively, with future cardiovascular disease events. While there are plausible mechanisms for most of these markers, it remains to be demonstrated whether the markers actually participate in cardiovascular disease, or simply reflect the underlying disease process. This point is important, since marker-specific interventions might be useful if the former position is correct. Recent work suggests that inflammation markers may represent different aspects of the atherothrombotic process at different points in the natural history of the disease. This has implications for the interpretation of marker levels and the timing of the future events that they predict.