Lipid Oxidative Markers Research Articles

LIPIDS AND ISCHEMIA MODIFIED ALBUMIN IN MILD SUBCLINICAL HYPOTHYROIDISM: RESPONSE TO LEVOTHYROXINE REPLACEMENT

Aim Subclinical hypothyroidism (SCH) with TSH less than (10µIU/ml) is a common finding discovered during routine thyroid function testing. Thyroxine substitution and its benefits to alleviate dyslipidemia and oxidative stress (OS) markers at this stage are a matter of debate.Material and Methods This study aimed to investigate the influence of thyroxine substitution on lipid profile and oxidative stress markers in newly diagnosed SCH subjects. The study included a total number of 50 newly diagnosed, (20 treated and 30 untreated) SCH subjects aged 20-50 years with (TSH < 10 μIU/ml) and FT4 levels in the normal range. Patients on medications that could cause thyroid hormone dysfunction, diabetes mellitus and current or pregnancy during the last two years were excluded. Serum TSH, T3, T4, FT4, Anti-thyroid peroxidase (TPO) antibodies, Total cholesterol (TC), High-density lipoprotein cholesterol (HDL), Triglycerides (TG), low-density lipoprotein cholesterol (LDL), ischemia-modified albumin (IMA) were determined in all subjects at baseline and after nine months.Results After Thyroxine replacement, a significant decrease in TSH, LDL, IMA and an increase in FT4 was observed. The decrease in TC was not statistically evident. There was no significant change in T3, T4, TG, HDL, after treatment. The untreated group showed an insignificant increase only in TSH.Conclusion Thyroid substitution therapy has a favorable influence on lipid profile and oxidative stress where it particularly reduced LDL and IMA.Key Words: Subclinical hypothyroidism, L-Thyroxine, Lipids, IMA, oxidative stress

Serum α-Hydroxybutyrate: A Candidate Marker of Insulin Resistance Is Associated with Deterioration in Anthropometric Measurements in Individuals with Low Diabetes Risk.

α-Hydroxybutyrate (α-HB) is a marker of insulin resistance (IR) and lipid oxidation, both of which precede the development of diabetes and cardiovascular disorders. We aimed to analyze the relation of α-HB levels with anthropometric measurements in individuals without metabolic risk factors. A total of 82 nonobese individuals [body mass index (BMI) <30 kg/m2] without an accompanying chronic disorder were enrolled into the study. The entire cohort of participants underwent physical examination. Biochemical and hormonal parameters were analyzed. The BMI was calculated as weight/height2 (kg/m2). An ELISA method was used to analyze serum α-HB level. The relation of variables was analyzed by correlation analysis. The mean age, BMI, body fat ratio, and waist/hip ratio of participants were 36 (9) years, 24.9 (2.2), 39.2 (3.9), and 0.82 (0.06), respectively. The mean fasting glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR) levels, total cholesterol, triglyceride, HDL, and LDL levels were 90.7 (5.1) mg/dL, 9.8 (1.5) IU/mL, 2.2 (0.3), 193.2 (32.6) mg/dL, 119.3 (60.3) mg/dL, 54.6 (12.2) mg/dL, and 114.2 (30.4) mg/dL, respectively. Serum α-HB level was significantly correlated with age, BMI, body fat ratio, waist circumference, waist/hip ratio, fasting glucose, insulin, HOMA-IR, HDL, total cholesterol, and triglyceride. Serum α-HB, a strong marker of insulin resistance, is well correlated with deterioration of anthropometric parameters such as an increase in BMI and body fat distribution in patients with low diabetes risk.

Lipid overload during gestation and lactation can independently alter lipid homeostasis in offspring and promote metabolic impairment after new challenge to high-fat diet

BackgroundNutritional status in early life is critically involved in the metabolic phenotype of offspring. However the changes triggered by maternal consumption of high-fat diet (HFD) in pre- or postnatal period should be better understood. Here we evaluated whether maternal HFD consumption during gestation and lactation could differently affect liver miR-122 and miR-370 expression leading to metabolic damages observed in offspring. Moreover, we investigate whether early overnutrition program offspring to more harmful response to HFD in later life.MethodsFemale mice were fed either a standard chow (SC) diet or a HFD three weeks before and during mating, gestation and/or lactation. Offspring were evaluated on the delivery day (d0), in a cross-fostering model at day 28 (d28) and in adult life, after a re-challenge with a HFD (d82).ResultsIn vitro analysis using liver cell line showed that palmitate could induced decrease in miR-122 and increase in miR-370 expression. Newborn pups (d0) from obese dams showed a decrease in lipid oxidation markers (Cpt1a and Acadvl), an increase in triacylglycerol synthesis markers (Agpat and Gpam), as well as lower miR-122 and higher miR-370 hepatic content that was inversely correlated to maternal serum NEFA and TAG. Pups fostered to SC dams presented an increase in body weight and Agpat/Gpam expression at d28 compared to pups fostered to HFD dams and an inverse correlation was observed between miR-122 hepatic expression and offspring serum TAG. In adult life (d82), the reintroduction of HFD resulted in higher body weight gain and hepatic lipid content. These effects were accompanied by impairment in lipid and glucose metabolism, demonstrated by reduced Cpt1a/Acadvl and increased Agpat/Gpam expression, lower glucose tolerance and insulin sensitivity.ConclusionOur data suggest that both gestational and lactation overnutrition results in metabolic changes that can permanently alter lipid homeostasis in offspring. The presence of fatty acids in maternal blood and milk seem to be responsible for modulating the expression of miR-122 and miR-370, which are involved in liver metabolism. These alterations significantly increase susceptibility to obesity and ectopic lipid accumulation and lead to a more harmful response to HFD in offspring.

Anti-aging effects of M2000 (β-D-mannuronic acid) as a novel immunosuppressive drug on the enzymatic and non-enzymatic oxidative stress parameters in an experimental model.

The anti-aging property of β-D-mannuronic acid (M2000) as a novel non-steroidal anti-inflammatory and immunosuppressive agent was investigated on several determinants relative to the oxidative stress in an animal model. Sprague-Dawley rats were used for evaluating the safety and efficacy properties of M2000 on some oxidative stress enzymes, including the following: mitochondrial superoxide dismutase (SOD2), catalase (CAT), glutathione peroxidase (GPX1), glutathione S-transferase (GST), myeloperoxidase (MPO), and inducible nitric oxide synthase (iNOS) gene expression by real-time PCR. Malondialdehyde (MDA), carbonyl protein (PCO) (the lipid and protein oxidation marker, respectively), and total antioxidant capacity (TAC) were tested in serum by biochemical analysis. In addition, cortisol as a steroid hormone was surveyed by chemiluminescence immunoassay after 12 weeks of M2000 consumption. The rats were sacrificed 3 months after daily oral administration of M2000. Our findings revealed the favorable effects of M2000 on several antioxidant enzyme and gene expression, including SOD2, CAT, GPX1, and GST; however, our results were not statistically significant. Moreover, there was no significant difference in MDA and PCO as lipid and protein oxidation markers, TAC, and cortisol compared with the control group following M2000 consumption. A slight weight increase in the M2000-treated group was also observed. Our data showed the anti-aging property of M2000 as a novel designed non-steroidal anti-inflammatory drug (NSAID) with immunosuppressive property on various oxidative stress determinants.

Attenuation of oxidative stress and cardioprotective effects of zinc supplementation in experimental diabetic rats.

Oxidative stress plays a major role in the pathogenesis of diabetes mellitus, which further exacerbates damage of cardiac, hepatic and other tissues. We have recently reported that Zn supplementation beneficially modulates hyperglycaemia and hypoinsulinaemia, with attendant reduction of associated metabolic abnormalities in diabetic rats. The present study assessed the potential of Zn supplementation in modulating oxidative stress and cardioprotective effects in diabetic rats. Diabetes was induced in Wistar rats with streptozotocin, and groups of diabetic rats were treated with 5- and 10-fold dietary Zn interventions (0·19 and 0·38 g Zn/kg diet) for 6 weeks. The markers of oxidative stress, antioxidant enzyme activities and concentrations of antioxidant molecules, lipid profile, and expressions of fibrosis and pro-apoptotic factors in the cardiac tissue were particularly assessed. Supplemental Zn showed significant attenuation of diabetes-induced oxidative stress in terms of altered antioxidant enzyme activities and increased the concentrations of antioxidant molecules. Hypercholesterolaemia and hyperlipidaemia were also significantly countered by Zn supplementation. Along with attenuated oxidative stress, Zn supplementation also showed significant cardioprotective effects by altering the mRNA expressions of fibrosis and pro-apoptotic factors (by >50 %). The expression of lipid oxidative marker 4-hydroxy-2-nonenal (4-HNE) protein in cardiac tissue of diabetic animals was rectified (68 %) by Zn supplementation. Elevated cardiac and hepatic markers in circulation and pathological abnormalities in cardiac and hepatic tissue architecture of diabetic animals were ameliorated by dietary Zn intervention. The present study indicates that Zn supplementation can attenuate diabetes-induced oxidative stress in circulation as well as in cardiac and hepatic tissues.

Hypolipidemic, antioxidant and anti-atherosclerogenic effect of aqueous extract leaves of Cassia. occidentalis Linn (Caesalpiniaceae) in diet-induced hypercholesterolemic rats

BackgroundHyperlipidemia and oxidative stress are major risk factors for atherosclerosis, and all three are among the most important risk factors for cardiovascular diseases. Cassia occidentalis aqueous extract has been used in African traditional medicine for the treatment of hypertension and associated cardiovascular diseases. This study was undertaken to evaluate the hypolipidemic and anti-atherosclerotic properties of the aqueous extract of the leaves of C. occidentalis in rats with hypercholesterolemia (HC).Sixty Normocholesterolemic (NC) male rats were divided into six groups (n = 10) and fed a high-cholesterol (HC) diet for 30 days (5 groups), or normal rat chow (normal control group). The plant extract was administered to animals at the increasing dose of 240, 320 and 400 mg/kg. After 4 weeks of treatment 5 rats out of 10 were sacrificed, blood samples, aorta, liver, and fresh faecal were collected and processed for biochemical tests. The experiments were conducted under the same conditions with a group of rat treated with Atorvastatin (1 mg/kg), used positive control. The effects of C. occidentalis on weight gain, water and food consumptions, levels of serum lipids and lipoprotein lipid oxidation and stress markers in blood and liver were also examined.ResultsA significant body weight gain was observed in general in all the group of animals without any treatment after 4 weeks. During the treatment period, the C. occidentalis extract induced a significant increase (P < 0.01) in water consumption and food intakes. After 4 weeks of treatment with hypercholesterolemia, the body temperature and organ weights including the liver, kidney, heart and the testis did not present any significant change. The administration of C. occidentalis extract significantly (p < 0.05) prevented the elevation in TC, LDL-C, VLDL-C, hepatic and aortic TG and TC. The atherogenic, triglycerides, and lipid peroxidation (TBARS) index were also decreased in the rats treated with the plant extract. C. occidentalis favoured the performance of faecal cholesterol. It also significantly inhibited the changes and the formation of aortic atherosclerotic plaques.ConclusionThis study provides evidence of hypolipidemic and antiatherosclerotic effects of C. occidentalis extract. C. occidenntalis aqueous extract reduced bad cholesterols, triglycerides and increasing good cholesterols in rats subjected to a feeding regime enriched with cholesterol. The results support the traditional use of the extract of this plant in the treatment of hypertension and diabetes.

Effect of Omega-3 Fatty Acids on Serum Lipid Profile and Oxidative Stress in Pediatric Patients on Regular Hemodialysis: A Randomized Placebo-Controlled Study

We sought to evaluate the effects of omega-3 fatty acids supplementation on serum lipid profile and oxidative stress markers in pediatric patients with end-stage renal disease on regular hemodialysis (HD). This study was a double-blinded, randomized, placebo-controlled trial conducted on 49 pediatric patients on regular HD for at least 6 months. Patients were randomly divided into either omega-3 group (n=25) who received 1-g oral omega-3 capsule once daily for 16weeks or placebo group (n=24) who received 1-g matching oral placebo capsule once daily for 16weeks. Lipid profile markers including: total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and oxidative stress markers including the following: malondialdehyde, glutathione peroxidase, and superoxide dismutase were measured at baseline and after 16weeks of supplementation. By the end of the study, children in omega-3 group showed a highly significant reduction in total cholesterol and a highly significant increase in glutathione peroxidase and superoxide dismutase levels. The administration of omega-3 has a beneficial effect on serum lipid profile and oxidative stress in children undergoing HD.

Nuclear receptors regulate lipid metabolism and oxidative stress markers in chondrocytes

Joint homeostasis failure can result in osteoarthritis (OA). Currently, there are no treatments to alter disease progression in OA, but targeting early changes in cellular behavior has great potential. Recent data show that nuclear receptors contribute to the pathogenesis of OA and could be viable therapeutic targets, but their molecular mechanisms in cartilage are incompletely understood. This study examines global changes in gene expression after treatment with agonists for four nuclear receptor implicated in OA (LXR, PPARδ, PPARγ, and RXR). Murine articular chondrocytes were treated with agonists for LXR, PPARδ, PPARγ, or RXR and underwent microarray, qPCR, and cellular lipid analyses to evaluate changes in gene expression and lipid profile. Immunohistochemistry was conducted to compare two differentially expressed targets (Txnip, Gsta4) in control and cartilage-specific PPARδ knockout mice subjected to surgical destabilization of the medial meniscus (DMM). Nuclear receptor agonists induced different gene expression profiles with many responses affecting lipid metabolism. LXR activation downregulated gene expression of proteases involved in OA, whereas RXR agonism decreased expression of ECM components and increased expression of Mmp13. Functional assays indicate increases in cell triglyceride accumulation after PPARγ, LXR, and RXR agonism but a decrease after PPARδ agonism. PPARδ and RXR downregulate the antioxidant Gsta4, and PPARδ upregulates Txnip. Wild-type, but not PPARδ-deficient mice, display increased staining for Txnip after DMM. Collectively, these data demonstrate that nuclear receptor activation in chondrocytes primarily affects lipid metabolism. In the case of PPARδ, this change might lead to increased oxidative stress, possibly contributing to OA-associated changes.Key messageNuclear receptors regulate metabolic genes in chondrocytes.Nuclear receptors affect triglyceride levels.PPARδ mediates regulation of oxidative stress markers.Nuclear receptors are promising therapeutic targets for osteoarthritis.

Probucol Protects Rats from Cardiac Dysfunction Induced by Oxidative Stress following Cardiopulmonary Resuscitation.

Objective To investigate the protective effect of probucol on induced cardiac arrest (CA) rats and possible mechanisms. Methods Sprague Dawley rats were orally administrated with probucol at different dosage or vehicle for 5 days and subjected to a CA model by electrical stimulation, followed by cardiopulmonary resuscitation (CPR). The return of spontaneous circulation (ROSC) rate, antioxidant enzyme activities, and lipid oxidation markers were measured in serum and myocardium. Hemodynamic parameters and myocardial functions of animals were analyzed. Expression of erythroid-derived 2-like 2 (NFE2L2) and Kelch-like ECH-associated protein 1 (KEAP1) in the myocardium were examined with immunohistochemistry. Results Probucol treatment significantly increased the ROSC rate and survival time of CA-induced rats. After ROSC, levels of oxidation-specific markers were decreased, while activities of antioxidant enzymes were increased significantly in probucol treatment groups. The probucol treatment improves hemodynamic parameters and myocardial functions. These parameter changes were in a dose-dependent manner. In the probucol treatment groups, the expression of KEAP1 was downregulated, while that of NFE2L2 was upregulated significantly. Conclusion In the CA-induced rat model, probucol dose dependently improved the ROSC rate, prolonged survival time, alleviated oxidative stress, and improved cardiac function. Such protective effects are possibly through regulations of the KEAP1-NFE2L2 system.

Supplementation of grazing beef cows during gestation as a strategy to improve skeletal muscle development of the offspring

The appropriate supply of nutrients in pregnant cows has been associated with the optimal development of foetal tissues, performance of their progeny and their meat quality. The aim of this study was to evaluate supplementation effects of grazing cows in different stages of gestation on skeletal muscle development and performance of the progeny. Thereby, 27 Nellore cows were divided into three groups (n=9 for each group) and their progeny as follows: UNS, unsupplemented during gestation; MID, supplemented from 30 to 180 days of gestation; LATE, supplemented from 181 to 281 days of gestation. The percentage composition of the supplement provided for the matrices was the following: ground corn (26.25%), wheat bran (26.25%) and soya bean meal (47.5%). The supplement was formulated to contain 30% CP. Supplemented matrices received 150 kg of supplement (1 and 1.5 kg/day for cows in the MID and LATE groups, respectively). After birth, a biopsy was performed to obtain samples of skeletal muscle tissue from calves to determine number and size of muscle fibres and for messenger RNA (mRNA) expression analysis. The percentage composition of the supplement provided for the progeny was the following: ground corn grain (30%), wheat bran (30%), soya bean meal (35%) and molasses (5%). The supplement was formulated to contain 25% CP and offered in an amount of 6 g/kg BW. Performance of the progeny was monitored throughout the suckling period. Means were submitted to ANOVA and regression, and UNS, MID and LATE periods of supplementation were compared. Differences were considered at P<0.10. Birth weight, average daily gain and weaning weight of the offspring did not differ among treatments (P>0.10). Similarly, no differences were observed between calves for nutrient intake (P>0.10). However, greater subcutaneous fat thickness (P=0.006) was observed in the calves of LATE group. The ribeye area (P=0.077) was greater in calves born from supplemented compared with UNS cows. The supplementation of pregnant cows did not affect the muscle fibre size of their progeny (P=0.208). On the other hand, calves born from dams supplemented at mid-gestation had greater muscle fibre number (P=0.093) compared with calves from UNS group. Greater mRNA expression of peroxysome proliferator-activated receptor α (P=0.073) and fibroblast growth factor 2 (P=0.003) was observed in the calves born from MID cows. Although strategic supplementation did not affect the BW of offspring, it did cause changes in carcass traits, number of myofibres, and mRNA expression of a muscle hypertrophy and lipid oxidation markers in skeletal muscle of the offspring.

Application of different thermal analysis techniques to characterize oxidized olive oils

The deep changes caused by oxidation on virgin olive oil (VOO), which is a high‐quality product, not subjected to ameliorative refining, make this phenomenon one of the most studied. Among the techniques used to study oxidation in olive oil, thermal analysis (TA) provides useful information about the thermal behavior of the samples as affected by oxidation. Thermogravimetry (TG), measuring the changes in the sample mass, can monitor the kinetics of oil mass loss in decomposition processes or oxidation and has been found particularly useful, especially when operating simultaneously with Differential Thermal Analysis (DTA) or Differential Scanning Calorimetry (DSC). The DSC thermal curves of olive oil, both on cooling and heating, has been found to be largely influenced by the oxidative status of the samples and different statistical approaches have been successfully proposed to correlate the thermal parameters with the conventional chemical indicators of oxidation. DSC can be also used to study the kinetics of phase transition phenomena as affected by oxidation. This review provides an exhaustive survey about the application of the thermoanalytical techniques on this topic proposing them as as a fast and green alternative to conventional chemical methods.Practical applications:The evaluation of the oxidative status of olive oil requires the development of simple and fast analytical techniques. The most used analytical methods are based on the chemical evaluation of the presence of molecules markers of lipid oxidation, but thermal analysis may provide a fast and green tool in this field, as it does not require sample preparation and use of solvents. The application of thermal analysis for the assessment of the oxidative degradation of olive oil has today reached numerous evidences that attest its actual applicability, and they are all summarized in this review. By these studies it is possible to put in evidence its ability to give qualitative information about the oxidative status of olive oil, both in terms of fatty substance degradation and presence of oxidation molecules that could be very helpful in the field of quality assurance for this high‐quality vegetable oil.Thermal analysis as a valuable tool to evaluate olive oil oxidation without sample preparation or use of solvents.

Markers of lipid oxidative damage in the exhaled breath condensate of nano TiO2 production workers

Nanoscale titanium dioxide (nanoTiO2) is a commercially important nanomaterial. Animal studies have documented lung injury and inflammation, oxidative stress, cytotoxicity and genotoxicity. Yet, human health data are scarce and quantitative risk assessments and biomonitoring of exposure are lacking. NanoTiO2 is classified by IARC as a group 2B, possible human carcinogen. In our earlier studies we documented an increase in markers of inflammation, as well as DNA and protein oxidative damage, in exhaled breath condensate (EBC) of workers exposed nanoTiO2. This study focuses on biomarkers of lipid oxidation. Several established lipid oxidative markers (malondialdehyde, 4-hydroxy-trans-hexenal, 4-hydroxy-trans-nonenal, 8-isoProstaglandin F2α and aldehydes C6–C12) were studied in EBC and urine of 34 workers and 45 comparable controls. The median particle number concentration in the production line ranged from 1.98 × 104 to 2.32 × 104 particles/cm3 with ∼80% of the particles <100 nm in diameter. Mass concentration varied between 0.40 and 0.65 mg/m3. All 11 markers of lipid oxidation were elevated in production workers relative to the controls (p < 0.001). A significant dose-dependent association was found between exposure to TiO2 and markers of lipid oxidation in the EBC. These markers were not elevated in the urine samples. Lipid oxidation in the EBC of workers exposed to (nano)TiO2 complements our earlier findings on DNA and protein damage. These results are consistent with the oxidative stress hypothesis and suggest lung injury at the molecular level. Further studies should focus on clinical markers of potential disease progression. EBC has reemerged as a sensitive technique for noninvasive monitoring of workers exposed to engineered nanoparticles.

Systemic Heme and Iron Overload Results in Depletion of Serum Hemopexin, Haptoglobin and Transferrin and Correlates with Markers of Endothelial Activation and Lipid Oxidation in Beta Thalassemia Major and Intermedia

Beta thalassemia is an inherited hemoglobinopathy due to reduced synthesis of Beta globin chains and, consequently, of hemoglobin A (a2b2). The clinical manifestations are mainly the result of chronic anemia and iron overload. The latter is due to increased iron absorption, induced by accelerated but ineffective erythropoiesis, and recurrent red blood cell transfusions. Alfa-chains and iron excess promote oxidative damage of red blood cell membrane, resulting in macrophage sequestration and extravascular hemolysis, and to a lower extent, in intravascular hemolysis, with consequent release of hemoglobin (Hb), heme and iron.Increasing evidence suggests that free heme exerts vasculotoxic, pro-inflammatory and procoagulant effects due to its ability to trigger endothelial and immune cells activation. In addition, a role for heme and iron has been postulated in the pathogenesis of other vascular diseases, including atherosclerosis. In mouse models of Beta thalassemia and sickle cell disease, circulating heme levels are elevated and correlate with the exhaustion of systemic scavengers for hemoglobin and heme, haptoglobin and hemopexin, respectively, as well as with severe endothelial dysfunction and inflammation. Hemopexin-based therapies significantly improve endothelial damage, vascular oxidative stress and inflammation in these mice (Vinchi et al., Circulation 2013, Blood 2016; Vercellotti GM. et al., Mol Med 2016).Whereas more data are reported on sickle patients in this regard, few data are available in patients with Beta thalassemia. In the present study, we examined serum samples from a cohort of 60 patients with Beta thalassemia major (age 11.5 ± 6.8, 44% males-56% females, Hb 7.69 ± 1.22 mg/dl, transfused every 3-4 weeks) and 7 patients with Beta thalassemia intermedia (age 14 ± 12 , 70% males-30% females, Hb 8.4 ± 0.74 mg/dl, transfused every 4-5 weeks). 10% of the patients received inconsistent iron chelation therapy. Serum from 10 healthy subjects (age 22.7±15.3, 50% males-50% females, Hb 13.12±1.15 mg/dl) served as control.Both groups of patients show high systemic heme and iron levels, which associate with a severe drop in serum haptoglobin, hemopexin and transferrin. Consistently, transferrin saturation (12.4±2 vs 79.6±24 %) and serum ferritin (55.14 ±0.23 vs 4919.2 ±2657.4 ng/ml) are elevated. Interestingly, these patients present with high systemic levels of the soluble adhesion molecules sVCAM-1 and sICAM-1, markers of enhanced endothelial activation. In addition, they show increased levels of serum malondialdehyde, a well-known marker of lipid peroxidation and oxidative stress, and high levels of circulating oxidized low density lipoproteins (oxLDL). All parameters significantly correlate with increased systemic heme and iron indices as well as decreased haptoglobin, hemopexin and transferrin levels.In conclusion, Beta thalassemia patients show a strong correlation between systemic heme and iron overload, depletion of the respective scavengers, and markers of oxidative stress and endothelial dysfunction, thus confirming studies in animal models. These results emphasize the involvement of serum hemoglobin, heme and iron in the pathophysiology of Beta thalassemia, including vascular dysfunction, and the key protective role of their carriers. These findings are relevant for disorders hallmarked by vasculopathy, such as sickle cell disease and Beta thalassemia, as well as cardiovascular diseases, such as atherosclerosis. Our data support the potential therapeutic benefit of the administration of hemoglobin/heme scavengers along with efficient iron chelation therapy to counteract heme- and iron-driven toxicity.(The last three authors equally contributed to the work)****P<0.0001 [Display omitted] DisclosuresVercellotti:CSL-Behring: Research Funding; Imara: Research Funding. Belcher:Cydan/Imara: Research Funding; CSL-Behring: Research Funding.

The NUTRAOLEOUM Study, a randomized controlled trial, for achieving nutritional added value for olive oils.

BackgroundVirgin olive oil, a recognized healthy food, cannot be consumed in great quantities. We aim to assess in humans whether an optimized virgin olive oil with high phenolic content (OVOO, 429 mg/Kg) and a functional one (FOO), both rich in phenolic compounds (429 mg/Kg) and triterpenic acids (389 mg/kg), could provide health benefits additional to those supplied a by a standard virgin olive oil (VOO).Methods/designA randomized, double-blind, crossover, controlled study will be conducted. Healthy volunteers (aged 20 to 50) will be randomized into one of three groups of daily raw olive oil consumption: VOO, OVOO, and FOO (30 mL/d). Olive oils will be administered over 3-week periods preceded by 2-week washout ones. The main outcomes will be markers of lipid and DNA oxidation, inflammation, and vascular damage. A bioavailability and dose-response study will be nested within this sustained- consumption one. It will be made up of 18 volunteers and be performed at two stages after a single dose of each olive oil. Endothelial function and nitric oxide will be assessed at baseline and at 4 h and 6 h after olive oil single dose ingestion.DiscussionFor the first time the NUTRAOLEUM Study will provide first level evidence on the health benefits in vivo in humans of olive oil triterpenes (oleanolic and maslinic acid) in addition to their bioavailability and disposition.Trial registrationThe Trial has been registered in ClinicalTrials.gov ID: NCT02520739.

Catechin and epicatechin reduce mitochondrial dysfunction and oxidative stress induced by amiodarone in human lung fibroblasts

BackgroundAmiodarone (AMD) and its metabolite N-desethylamiodarone can cause some adverse effects, which include pulmonary toxicity. Some studies suggest that mitochondrial dysfunction and oxidative stress may play a role in these adverse effects. Catechin and epicatechin are recognized as important phenolic compounds with the ability to decrease oxidative stress. Therefore, the aim of this study was to evaluate the potential of catechin and epicatechin to modulate mitochondrial dysfunction and oxidative damage caused by AMD in human lung fibroblast cells (MRC-5). MethodsMitochondrial dysfunction was assessed through the activity of mitochondrial complex I and ATP biosynthesis. Cell viability was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Superoxide dismutase and catalase activity were measured spectrophotometrically at 480 and 240nm, respectively. Lipid and protein oxidative levels were determined by thiobarbituric reactive substances and protein carbonyl assays, respectively. Nitric oxide (NO) levels were evaluated using the Griess reaction method. ResultsAMD was able to inhibit the activity of mitochondrial complex I and ATP biosynthesis in MRC-5 cells. Lipid and protein oxidative markers increased along with cell death, while superoxide dismutase and catalase activities and NO production decreased with AMD treatment. Both catechin and epicatechin circumvented mitochondrial dysfunction, thereby restoring the activity of mitochondrial complex I and ATP biosynthesis. Furthermore, the phenolic compounds were able to restore the imbalance in superoxide dismutase and catalase activities as well as the decrease in NO levels induced by AMD. Protein and lipid oxidative damage and cell death were reduced by catechin and epicatechin in AMD-treated cells. ConclusionsCatechin and epicatechin reduced mitochondrial dysfunction and oxidative stress caused by AMD in MRC-5 cells.

Markers of lipid oxidative damage among office workers exposed intermittently to air pollutants including nanoTiO2 particles.

Nanoscale titanium dioxide (nanoTiO2) is a commercially important nanomaterial used in numerous applications. Experimental studies with nanotitania have documented lung injury and inflammation, oxidative stress, and genotoxicity. Production workers in TiO2 manufacturing with a high proportion of nanoparticles and a mixture of other air pollutants, such as gases and organic aerosols, had increased markers of oxidative stress, including DNA and protein damage, as well as lipid peroxidation in their exhaled breath condensate (EBC) compared to unexposed controls. Office workers were observed to get intermittent exposures to nanoTiO2 during their process monitoring. The aim of this study was to investigate the impact of such short-term exposures on the markers of health effects in office workers relative to production workers from the same factory. Twenty-two office employees were examined. They were occupationally exposed to (nano)TiO2 aerosol during their daily visits of the production area for an average of 14±9 min/day. Median particle number concentration in office workers while in the production area was 2.32×104/cm3. About 80% of the particles were <100 nm in diameter. A panel of biomarkers of lipid oxidation, specifically malondialdehyde (MDA), 4-hydroxy-trans-hexenal (HHE), 4-hydroxy-trans-nonenal (HNE), 8-isoprostaglandin F2α (8-isoprostane), and aldehydes C6-C12, were studied in the EBC and urine of office workers and 14 unexposed controls. Nine markers of lipid oxidation were elevated in the EBC of office employees relative to controls (p<0.05); only 8-isoprostane and C11 were not increased. Significant association was found in the multivariate analysis between their employment in the TiO2 production plant and EBC markers of lipid oxidation. No association was seen with age, lifestyle factors, or environmental air contamination. The EBC markers in office employees reached about 50% of the levels measured in production workers, and the difference between production workers and office employees was highly significant (p<0.001). None of these biomarkers were elevated in urine. The approach presented here seems to be very sensitive and useful for non-invasive monitoring of employees exposed to air pollutants, including gases, organic aerosols, and nanoTiO2, and may prove useful for routine biomonitoring purposes. Among them, aldehydes C6, C8, C9, and C10 appear to be the most sensitive markers of lipid oxidation in similar occupational cohorts. One major challenge with sensitive biomonitoring techniques, however, is their non-specificity and difficulty in interpreting the meaning of their physiological values in the context of chronic disease development and damage-repair kinetics.

Effect of different intensities of physical activity on cardiometabolic markers and vascular and cardiac function in adult rats fed with a high-fat high-carbohydrate diet

BackgroundPhysical activity (PA) and diet are 2 lifestyle factors that affect cardiometabolic risk. However, data on how a high-fat high-carbohydrate (HFHC) diet influences the effect of different intensities of PA on cardiometabolic health and cardiovascular function in a controlled setting are yet to be fully established. This study investigated the effect of sedentary behavior, light-intensity training (LIT), and high-intensity interval training (HIIT) on cardiometabolic markers and vascular and cardiac function in HFHC-fed adult rats. MethodsTwelve-week-old Wistar rats were randomly allocated to 4 groups (12 rats/group): control (CTL), sedentary (SED), LIT, and HIIT. Biometric indices, glucose and lipid control, inflammatory and oxidative stress markers, vascular reactivity, and cardiac electrophysiology of the experimental groups were examined after 12 weeks of HFHC-diet feeding and PA interventions. ResultsThe SED group had slower cardiac conduction (p = 0.0426) and greater thoracic aortic contractile responses (p < 0.05) compared with the CTL group. The LIT group showed improved cardiac conduction compared with the SED group (p = 0.0003), and the HIIT group showed decreased mesenteric artery contractile responses compared with all other groups and improved endothelium-dependent mesenteric artery relaxation compared with the LIT group (both p < 0.05). The LIT and HIIT groups had lower visceral (p = 0.0057 for LIT, p = 0.0120 for HIIT) and epididymal fat (p < 0.0001 for LIT, p = 0.0002 for HIIT) compared with the CTL group. ConclusionLIT induced positive adaptations on fat accumulation and cardiac conduction, and HIIT induced a positive effect on fat accumulation, mesenteric artery contraction, and endothelium-dependent relaxation. No other differences were observed between groups. These findings suggest that few positive health effects can be achieved through LIT and HIIT when consuming a chronic and sustained HFHC diet.

Brief Communication: Plasma lipid oxidation predicts atherosclerotic status better than cholesterol in diabetic apolipoprotein E deficient mice.

Increased levels of oxidative stress have been suggested to play a detrimental role in the development of diabetes-related vascular complications. Here, we investigated whether the concentration of malondialdehyde, a marker of lipid oxidation correlated to the degree of aortic plaque lesions in a proatherogenic diabetic mouse model. Three groups of apolipoprotein E knockout mice were studied for 20 weeks, a control, a streptozotocin-induced diabetic, and a diabetic enalapril-treated group. Enalapril was hypothesized to lower oxidative stress level and thus the plaque burden. Both diabetic groups were significantly different from the control group as they had higher blood glucose, HbA1c, total cholesterol, low-density lipoprotein, very low-density lipoprotein, together with a lower high-density lipoprotein concentration and body weight. Animals in the diabetic group had significantly higher plaque area and plasma malondialdehyde than controls. The two diabetic groups did not differ significantly in any measured characteristic. In summary, there was a positive correlation between plasma malondialdehyde concentration and aorta plaque area in apolipoprotein E knockout. Even though further investigation of the role of lipid oxidation in the development of atherosclerosis is warranted, these results suggest that biomarkers of lipid oxidation may be of value in the evaluation of cardiovascular risk.

Effect of intermittent frying on fatty acids, vitamin E, lipid oxidation and acrylamide in oils and plantain chips collected from small- scale producers in Cameroon

Deep-fat frying is susceptible to induce the formation of undesirable products as lipid oxidation products and acrylamide in fried foods. Plantain chips produced by small-scale producers are sold to consumers without any control. The objective of this study was to evaluate the quality of plantain chips from local producers in relation to production process parameters and oils, and to identify the limiting factors for the production of acrylamide in plantain chips. Samples of frying oils and plantain chips prepared with either palm olein or soybean oil were collected from 10 producers in Yaounde. Quality parameters determined in this study were: fatty acid composition of the oils, determined by gas chromatography (GC) of free acid methyl ester; trans fatty acids, determined by Fourier transform infra-red spectroscopy; Tocopherols and tocotrienols as markers of nutritional quality were analyzed by High Performance Liquid Chromatography in isocratic mode. Free fatty acids and acylglycerols as markers of lipid hydrolysis were analyzed by GC of trimethylsilyl derivatives of glycerides. Conjugated dienes, Anisidine value and viscosity as markers of lipid oxidation and thermal decomposition of the oils; acrylamide which is formed through Maillard reaction and identified as a toxic compound in various fried products. Asparagine content of the raw fresh plantain powder was also determined. Fatty acid composition of palm oleins was stable within a day of intermittent frying. In soybean oils, about 57% and 62.5% of linoleic and linolenic acids were lost but trans fatty acids were not detected. Soybean oils were partly hydrolysed leading to the formation of free fatty acids, monoacylglycerols and diacylglycerols. In both oils, tocopherols and tocotrienols contents decreased significantly by about 50%. Anisidine value (AV) and polymers contents increased slightly in fried palm oleins while conjugated hydroperoxides, AV and polymers greatly increased in soybean oils. Acrylamide was not detected in the chips. This is explained by the absence of asparagine in the raw plantains, the other acrylamide precursors being present. This study shows that the plantain chips prepared at the small-scale level in Yaounde with palm olein are of good quality regarding oxidation and hydrolysis parameters and the absence of acrylamide. In contrast, oxidation developed with soybean oil whose usage for frying should be questioned. Considering that asparagine is the limiting factor for the formation of acrylamide in plantain chips, its content depending on several factors such as production parameters and maturity stage should be explored. Keywords: frying, plantain, producers, palm olein, soybean oil, oxidation, acrylamide, asparagine

Effect of dietary supplementation of garlic and vitamin E on lipid and protein oxidation in common carp meat during different storage times

This study was conducted to investigate the effects of dietary garlic powder and vitamin E supplement for 6 weeks on lipid and protein oxidation markers in nonfrozen and frozen carp meat at various time intervals. Fish were divided into four groups: Group 1 served as control; Group 2 and 3 received 25 and 50 g/kg diet garlic powder, respectively; Group 4 received diet supplemented with 150 mg/kg vitamin E. Based on the results, meat malondialdehyde (MDA) concentrations showed a significant (p < 0.05) decrease after 12, 48, 72 and 96 hours storage at 4 °C and after a storage period of 1 and 3 months at -20 °C in all treatment groups as compared to the control group. Carbonyl groups accumulation was found to be significantly reduced at 6 hours (in group 4), at 12 hours (in groups 3 and 4) and at 24, 48, 72 and 96 hours (in all treatment groups) after storage at 4 °C compared to the control group. Alpha-tocopheryl acetate supplementation resulted in the lowest MDA and protein carbonyl contents relative to garlic supplementation. It can be concluded that both studied compounds are notably effective against lipid and protein oxidation of carp meat during storage.