Relevance of oxidative stress biomarkers, hemoglobin A1c, troponin-I, and angiotensin-converting enzyme metabolism to blood pressure in acute myocardial infarction: a case-control study.

The aim was to investigate this relationship by calculating 1) the correlation between peak troponin-C (peak-cTnI), levels of oxidative stress biomarkers, including lipid peroxidation products (malondialdehyde (MDA), conjugated dienes (CD)), and antioxidant enzyme activity (glutathione peroxidase (GPx)), and HbA1c and 2) the correlation between HbA1c and serum angiotensin-converting enzyme (ACE) activity, and its impact on the rate pressure product (RPP) in acute myocardial infarction (AMI). A case-control study was performed in 306 AMI patients having undergone coronary angiography and on 410 controls. GPx activity was reduced in association with increased MDA and CD in patients. Peak-cTnI was positively correlated with HbA1c, MDA, and CD levels. Serum ACE activity was negatively correlated with GPx. HbA1c was positively correlated with ACE activity and RPP. Linear regression analysis showed that peak-cTnI, ACE activity and HbA1c are significant predictors of AMI. Elevated HbA1c and peak-cTnI levels are associated with RPP elevation causing AMI. In conclusions, patients with elevated HbA1c, elevated ACE activity and cTnI are at increased risk of AMI with increasing RPP. Patients at risk of AMI can be identified at an early stage if the biomarkers HbA1c, ACE activity, and cTnI are measured and preventive measures are taken in a targeted manner.

Nigella and Milk Thistle Seed Oils: Potential Cytoprotective Effects against 7ß-Hydroxycholesterol-Induced Toxicity on SH-SY5Y Cells.

Oxysterols are assumed to be the driving force behind numerous neurodegenerative diseases. In this work, we aimed to study the ability of 7ß-hydroxycholesterol (7ß-OHC) to trigger oxidative stress and cell death in human neuroblastoma cells (SH-SY5Y) then the capacity of Nigella sativa and Milk thistle seed oils (NSO and MTSO, respectively) to oppose 7ß-OHC-induced side effects. The impact of 7ß-OHC, associated or not with NSO or MTSO, was studied on different criteria: cell viability; redox status, and apoptosis. Oxidative stress was assessed through the intracellular reactive oxygen species (ROS) production, levels of enzymatic and non-enzymatic antioxidants, lipid, and protein oxidation products. Our results indicate that 7ß-OHC (40 µg/mL) exhibit pr-oxidative and pro-apoptotic activities shown by a decrease of the antioxidant enzymatic activities and an increase of ROS production, lipid, and protein oxidation end products as well as nitrotyrosine formation and caspase 3 activation. However, under the pre-treatment with NSO, and especially with MTSO (100 µg/mL), a marked attenuation of oxidative damages was observed. Our study suggests harmful effects of 7ß-OHC consisting of pro-oxidative, anti-proliferative, and pro-apoptotic activities that may contribute to neurodegeneration. NSO and especially MTSO showed potential cytoprotection against the cytotoxicity of 7ß-OHC.

Association Between Oxidative Stress and Altered Cholesterol Metabolism in Alzheimer's Disease Patients.

BACKGROUND: Oxidative stress is the main feature of several diseases including Alzheimer's disease (AD). The involvement of oxysterols derivates has been recently reported. OBJECTIVE: The aim of this study was to evaluate the implication of oxidative stress in cholesterol impairment in AD patients. METHODS: A case-control study was conducted on 56 AD patients and 97 controls. Levels of oxidative biomarkers, including lipid peroxidation products and antioxidant enzyme activities were measured with spectrophotometric methods on red blood cells (RBCs) and plasma. Cholesterol precursors and oxysterols (7-Ketocholeterol (7KC), 7α-hydroxycholesterol (7α-OHC), 7ß-hydroxycholesterol (7ß-OHC), 24Shydroxycholesterol (24S-OH), 25-hyroxycholesterol (25-OHC), and 27-hydroxycholesterol (27-OHC), in plasma were quantified by gas chromatography coupled with mass spectrometry. RESULTS: In RBCs and plasma of AD patients, a significant decrease of glutathione peroxidase (GPx) activity was detected associated with raised levels of malondialdehyde (MDA). A decreased level of lanosterol and an accumulation of 7ß-OHC, 24S-OHC, 27-OHC, and 25-OHC that were higher in plasma of AD patients, compared to controls, were also observed in AD patients. Mini-Mental State Examination (MMSE) score was correlated with MDA and conjugated dienes (CD) levels in plasma. Besides, the MDA level in RBCs was correlated with 7ß-OHC. Binary logistic regression revealed an association between GPx activity and AD (OR=0.895, 95%CI: 0.848-0.945. P<0.001). CONCLUSION: Our data consolidate the relationship between the rupture of redox homeostasis and lipid and cholesterol oxidation in AD.

Genetic variants in FADS1 and ELOVL2 increase level of arachidonic acid and the risk of Alzheimer's disease in the Tunisian population.

Polyunsaturated fatty acids (PUFAs) are closely related to various physiological conditions. In several age-related diseases including Alzheimer's disease (AD) altered PUFAs metabolism has been reported. However, the mechanism behind PUFAs impairment and AD developpement remains unclear. In humans, PUFAs biosynthesis requires delta-5 desaturase (D5D), delta-6 desaturase (D6D) and elongase 2 activities; which are encoded by fatty acid desaturase 1 (FADS1), fatty acid desaturase 2 (FADS2), and elongation of very-long-chain fatty acids-like 2 (ELOVL2) genes, respectively. In the present work, we aim to assess whether genetic variants in FADS1, FADS2 and ELOVL2 genes influence plasma and erythrocyte PUFA composition and AD risk. A case-control study was carried out in 113 AD patients and 161 healthy controls.Rs174556, rs174617, and rs3756963 of FADS1, FADS2, and ELOVL2 genes, respectively were genotyped using PCR-RFLP. PUFA levels were quantified using Gas Chromatography. Genotype distributions of rs174556 (FADS1) and rs3756963 (ELOVL2) were different between case and control groups. The genotype TT of rs174556 and rs3756963 single nucleotide polymorphism (SNP) increases significantly the risk of AD in our population. PUFA analysis showed higher plasma and erythrocyte arachidonic acid (AA) level in patients with AD, whereas only plasma docosahexaenoic acid (DHA) was significantly decreased in AD patients. The indexes AA/Dihomo-gamma-linolenic acid (DGLA) and C24:4n-6/Adrenic acid (AdA) were both higher in the AD group. Interestingly, patients with TT genotype of rs174556 presented higher AA level and AA/DGLA index in both plasma and erythrocyte. In addition, higher AA and AA/DGLA index were observed in erythrocyte of TT genotype ofrs3756963 carrier's patients. Along with, positive correlation between AA/DGLA index, age or Gamma-linolenic acid (GLA)/ Linoleic acid (LA) index was seen in erythrocyte and /or plasma of AD patients. After adjustment for confounding factors, the genotype TT of rs174556, erythrocyte AA and AA/DGLA index were found to be predictive risk factors for AD while plasma DHA was found associated with lower AD risk. Both rs174556 and rs3756963 influence AD risk in the Tunisian population and they are likely associated with high AA level. The combination of the two variants increases further the susceptibility to AD. We suggest that FADS1 and ELOVL2 variants could likely regulate the efficiency of AA biosynthesis which could be at the origin of inflammatory derivate.

Association Between Genetic Variants in FADS1-FADS2 and ELOVL2 and Obesity, Lipid Traits, and Fatty Acids in Tunisian Population.

The aim of this study was to determine whether genetic variants in FADS1/FADS2 and ELOVL2 are associated with overweight-obesity and body mass index (BMI) and to assess the association between these genetic variants and lipid profile and fatty acid levels. A total of 259 overweight-obese patients were compared to 369 healthy controls. FADS1, FADS2, and ELOVL2 genes were associated with BMI and overweight-obesity (P ≤ .001). In an additive model, the C allele in each of these variants was associated with a lower BMI: -1.18, -0.90, and -1.23 units, respectively. Higher amounts of total cholesterol, low-density lipoprotein cholesterol, total saturated fatty acids (lauric [12:0], myristic [C14:0], palmitic [C16:0], stearic [C18:0], arachidic [20:0], lignoceric [24:0]), monounsaturated fatty acids (myristoleic [C14:1], erucic [C22:1 n-9]), and polyunsaturated fatty acids (α-linolenic [ALA, 18:3 n-3], docosahexaenoic [DHA, C22:6 n-3], eicosapentaenoic acid [EPA, C20:5n-3], arachidonic acid [AA, 20:4n-6], and conjugated linolenic acids [CLA1 and CLA2]) were shown in patients. A significant increase in D6D activities presented by 20:4n-6/18:2n-6 and 18:3n-6/18:2n-6, Δ9 desaturase (D9D) activity, estimated by the ratio 18:1n-9/18:0 and elongase activities (AE), and estimated by the ratio of docosatetraenoic/AA and DPA/EPA in patients. The C minor allele of FADS1 had significantly lower DHA. A significant decrease in stearic acid, EPA, and AE activity (docosatetraenoic/AA) was revealed in patients with the minor allele carriers of FADS2. The C minor allele of ELOVL2 had significantly lower ALA, EPA, DPA, and D6D activity (C20:4 n-6/C18:2n-6). These data suggest that variations in FADS1, FADS2, and ELOVL2 affect the risk of overweight-obesity and the level of circulating fatty acids and could point to a key molecular pathway of metabolic syndrome and its related comorbidities.

Association of angiotensin-converting enzyme insertion/deletion (ACE I/D) and angiotensinogen (AGT M235T) polymorphisms with the risk of obesity in a Tunisian population.

OBJECTIVE: This study aims to determine whether genetic variants in ACE I/D and AGT M235T are associated with overweight-obesity and body mass index (BMI) in a Tunisian population. METHODS: We designed an age- and sex-matched case-control study. The height and weight were measured and BMI was calculated. A total of 259 overweight-obese patients and 369 healthy controls were genotyped for the ACE I/D and AGT M235T genes using polymerase chain reaction and restriction fragment length polymorphism. RESULTS: ACE I/D and AGT M235T genes were associated with BMI, waist circumference and overweight-obesity (p⩽0.001). In an additive model, the I and the M alleles in ACE and AGT variants, respectively, were associated with a lower BMI: -1.45 and -2.29 units, respectively. ACE I/D genotypes were associated with dyslipidemia; AGT M235T genotypes with dyslipidemia and total cholesterol. CONCLUSION: These data suggest that variations in ACE I/D and AGT M235T affect the risk of overweight-obesity, BMI and dyslipidemia, and could point to a key molecular pathway of metabolic syndrome and its related comorbidities.