Early Oxidative Stress Response in Patients with Severe Aortic Stenosis Undergoing Transcatheter and Surgical Aortic Valve Replacement: A Transatlantic Study.

Myocardial ischemia/reperfusion-related oxidative stress as a result of cardiopulmonary bypass is thought to contribute to the adverse clinical outcomes following surgical aortic valve replacement (SAVR). Although the acute response following this procedure has been well characterized, much less is known about the nature and extent of oxidative stress induced by the transcatheter aortic valve replacement (TAVR) procedure. We therefore sought to examine and directly compare the oxidative stress response in patients undergoing TAVR and SAVR. A total of 60 patients were prospectively enrolled in this exploratory study, 38 patients undergoing TAVR and 22 patients SAVR. Reduced and oxidized glutathione (GSH, GSSG) in red blood cells as well as the ferric-reducing ability of plasma (FRAP) and plasma concentrations of 8-isoprostanes were measured at baseline (S1), during early reperfusion (S2), and 6-8 hours (S3) following aortic valve replacement (AVR). TAVR and SAVR were successful in all patients. Patients undergoing TAVR were older (79.3 ± 9.5 vs. 74.2 ± 4.1 years; P < 0.01) and had a higher mean STS risk score (6.6 ± 4.8 vs. 3.2 ± 3.0; P < 0.001) than patients undergoing SAVR. At baseline, FRAP and 8-isoprostane plasma concentrations were similar between the two groups, but erythrocytic GSH concentrations were significantly lower in the TAVR group. After AVR, FRAP was markedly higher in the TAVR group, whereas 8-isoprostane concentrations were significantly elevated in the SAVR group. In conclusion, TAVR appears not to cause acute oxidative stress and may even improve the antioxidant capacity in the extracellular compartment.

Plasma versus Erythrocyte Vitamin E in Renal Transplant Recipients, and Duality of Tocopherol Species.

Redox imbalance is an adverse on-going phenomenon in renal transplant recipients (RTR). Vitamin E has important antioxidant properties that counterbalance its deleterious effects. However, plasma vitamin E affinity with lipids challenges interpretation of its levels. To test the hypothesis that erythrocyte membranes represent a lipids-independent specimen to estimate vitamin E status, we performed a cross-sectional study in a cohort of adult RTR (n = 113) recruited in a university setting (2015-2018). We compared crude and total lipids-standardized linear regression-derived coefficients of plasma and erythrocyte tocopherol species in relation to clinical and laboratory parameters. Strongly positive associations of fasting lipids with plasma tocopherol became inverse, rather than absent, in total lipids-standardized analyses, indicating potential overadjustment. Whilst, no variables from the lipids domain were associated with the tocopherol species measured from erythrocyte specimens. In relation to inflammatory status and clinical parameters with antioxidant activity, we found associations in directions that are consistent with either beneficial or adverse effects concerning α- or γ-tocopherol, respectively. In conclusion, erythrocytes offer a lipids-independent alternative to estimate vitamin E status and investigate its relationship with parameters over other biological domains. In RTR, α- and γ-tocopherol may serve as biomarkers of relatively lower or higher vulnerability to oxidative stress and inflammation, noticeably in opposite directions.

Clinical decision making in postmastectomy radiotherapy in node negative breast cancer.

For decades, postmastectomy radiotherapy (PMRT) has been recommended for node positive [N(+)] breast cancer patients; nevertheless, the beneficial effect of PMRT for treatment of node negative [N(-)] disease remains under discussion. Nowadays, the biology of breast cancer and the risk factors (RFs) for locoregional failure (LRF) must be included in the decision on whether or not to carry out PMRT. For these reasons, the present review aims to evaluate the rationale use of PMRT in N(-) patients and discuss which subgroups may further benefit from the treatment in present times where the decision must be personalised, according to the RFs of locoregional recurrence (LRR). To perform the analysis, we ponder that LRR of over 10% should be considered unacceptable due to the fact that LRRs generate great morbidity in patients. For this purpose, we consider that routine RT in these patients is not recommended, although there are subgroups of patients with high LRR, in which PMRT could be beneficial.

Role of Oxidative Stress in Renal Transplantation: Bases for an n-3 PUFA Strategy Against Delayed Graft Function.

Renal transplantation (RT) is considered the "gold standard" treatment for end-stage renal disease patients. Efforts should be made to reduce ischaemia-reperfusion (IR) injury, which unavoidably occurs in RT as long as several clinical settings, i.e. open-heart surgeries, prosthesis implantation, among others. It is well known that IR is primarily responsible for injury associated with RT. Consequently, tissue inflammation and organ dysfunction will ensue due to the occurrence of oxidative stress (OS) in the reperfused tissue, a condition generated when endogenous antioxidant defences become overwhelmed by a massive production of reactive oxygen species. Furthermore, OS is involved in the impairment of renal function, leading to deleterious conditions such as delayed graft function (DGF), which is a common clinical expression of IR injury in RT. Omega-3 polyunsaturated fatty acids (n -3 PUFA) have been widely used in different clinical settings to counteract the deleterious effects of OS. Thus, based on the currently available literature, the central aim of this review was to propose an n-3 PUFAbased strategy targeting the key role of OS in the pathophysiology of renal IR injury in order to encourage protection against the occurrence of DGF.

Potential Role of Polyphenols in the Prevention of Cardiovascular Diseases: Molecular Bases.

Cardiovascular diseases (CVD) are the leading cause of mortality worldwide. It is widely accepted that oxidative stress plays a key role in their development and progression; hence oxidative damage might be abrogated by antioxidants. Polyphenols are phytochemicals showing extensively studied antioxidant properties in-vivo. Most representative sources of these compounds include fruits, greens, nuts, herbs, cocoa, tea and coffee. Epidemiological evidence suggests an association between the consumption of polyphenol-rich vegetables and the reduction of cardiovascular disease prevalence. This fact could be related to the anti-inflammatory, antithrombotic and vasodilatory effects of polyphenols. Even though these biological effects could be mainly attributed to the antioxidant activity of polyphenols, other pharmacological mechanisms should also be considered. The latter could comprise direct anti-inflammatory effects, modulation of intracellular signaling and gene expression, improvement of nitric oxide homeostasis, as well as platelet antiaggregation. However, it is noticeable that protocols of interventions to evaluate the properties of polyphenols have failed to show the same positive results reported from observational studies. At present, a controversy exists regarding the actual effectiveness of polyphenols in preventing cardiovascular diseases. Therefore, an improvement of the available knowledge about polyphenol pharmacokinetics, together with a better understanding of the mechanisms of action of these compounds, could be of great benefit. Thus, a rational support for the development of interventional designs could provide reliable evidence on the actual role of polyphenols in CVD prevention.

Novel relationships between oxidative stress and angiogenesis-related factors in sepsis: New biomarkers and therapies.

Sepsis is a systemic uncontrolled inflammatory response in the presence of an infection. It remains a major cause of morbidity and mortality in hospitalized patients. According to its severity, sepsis can progress to three different states: severe sepsis, septic shock, and multiple organ dysfunction syndrome, related to organ dysfunction and/or tissue hypoperfusion. Different processes underlie its pathophysiology; among them are oxidative stress, endothelial and mitochondrial dysfunction, and angiogenesis-related factors. However, no studies have integrated these elements in sepsis. The main difficulty in sepsis is its diagnosis. Currently, the potential of inflammatory biomarkers in septic patients remains weak. In this context, the research into new biomarkers is essential to aid with sepsis diagnosis and prognostication. Furthermore, even though the current management of severe forms of sepsis has been effective, morbimortality remains elevated. Therefore, it is essential to explore alternative approaches to therapy development. The aim of this review is to present an update of evidence supporting the role of oxidative stress and angiogenesis-related factors in the pathophysiology of the different forms of sepsis. It proposes a novel convergence between both elements in their role in the disease, and it will cover their utility as new diagnostic tools, predictors of outcome, and as novel therapeutic targets.

Cardiovascular Disease: A Target for the Pharmacological Effects of Quercetin.

Quercetin, a prominent dietary antioxidant present in vegetables, especially onions, fruits, highlighting apples and berries, wine and tea, belongs to a group of plant derived heterocyclic polyphenols. These compounds could be important mediators of the biological actions attributed to healthy diets. Chemically, quercetin is a type of flavonoid that specifically belongs to the flavonols group. It naturally occurs either as glycoside or aglycone, both of which have biological activity. Many of the natural sources of quercetin are included in the Mediterranean diet, a dietary habit associated with a decrease of cardiovascular diseases. During the last years, several researches have reported effects consistent with pharmacological applications of quercetin in cardiovascular diseases, such as atherosclerosis, ischemia-reperfusion injury, cardiotoxicity, and hypertension, among others. In this review, the pathways and molecules involved in the beneficial effects of quercetin are summarized. In addition, a scope of the new insights concerning quercetin pharmacokinetics, pharmacodynamics and bioavailability are presented. The mechanisms whereby quercetin exerts its effects have not been fully elucidated. However, interesting results have been obtained from early clinical studies involving cardioprotection by quercetin, but much knowledge is still lacking in the field of its bioavailability to improve the clinical application of this flavonol. This study presents evidence supporting the point of view that quercetin should be considered a potential therapeutic agent against cardiovascular diseases, giving rise to novel applications in their prevention and treatment.

Prevention of liver steatosis through fish oil supplementation: correlation of oxidative stress with insulin resistance and liver fatty acid content / Prevención de la esteatosis hepática mediante suplementación con aceite de pescado: correlación de los niveles hepáticos de ácidos grasos poliinsaturados con el estrés oxidativo y la resistencia a la insulina

Non-alcoholic fatty liver disease (NAFLD) is triggered by a nutritional-metabolic alteration characterized by triacylglicerides acumulation, insulin resistance (IR), oxidative stress and depletion of polyunsaturated fatty acid (PUFA). The n-3 PUFA, such as eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids, would be hepatoprotective against the development of NAFLD by stimulating lipolysis and inhibit lipogenesis. So, fish oil supplementation (EPA + DHA) prevents HFDinduced NAFLD. In this context, the aim of this study is to evaluate the correlation between liver oxidative stress with IR and levels of PUFA in supplemented mice. Male mice C57BL/6J (n=9) were fed for 12th week: a) control diet (20% protein, 70% carbohydrate, 10% lipids), b) control diet and fish oil supplementation (200 mg EPA+DHA/kg/day), c) high fat diet (20% protein, 20% carbohydrate, 60% lipids), and d) high fat diet and fish oil supplementation. Liver steatosis (histology), insulin resistance (HOMA), liver oxidative stress (GSH/GSSG, carbonyl protein and 8-isoprostanes) and liver fatty acid content were evaluated. The significant decrease in liver oxidative stress parameters (p<0.05, ANOVA followed by Newman Keuls test) were correlated (Pearson test) with HOMA and levels of PUFA, along with the hepatoprotection observed. It concludes that prevention of NAFLD by supplementation with fish oil (EPA+DHA) is dependent of the prevention of liver oxidative stress, IR and PUFA depletion.

La enfermedad por hígado graso no alcohólica (EHGNA) está provocada por una alteración metabólico- nutricional caracterizada por la acumulación de triacilglicéridos, resistencia a la insulina, estrés oxidativo y disminución de ácidos grasos poliinsaturados (AGPI). Los AGPI ω-3, como los ácidos eicosapentaenoico (EPA) y docosahexaenoico (DHA), serían hepatoprotectores contra la EHGNA al estimular la lipolisis e inhibir la lipogénesis hepática. La suplementación con aceite de pescado (EPA + DHA) previene la esteatosis hepática inducida por una dieta alta en grasas. En este contexto, el objetivo de este estudio es evaluar la correlación entre el estrés oxidativo hepático, la resistencia a la insulina y los niveles de AGPI ω-3 en ratones suplementados. Ratones machos C57BL/6J (n=9) alimentados durante 12 semanas con: a) dieta control (20% proteína, 70% hidratos de carbono, 10% lípidos), b) dieta control y suplementación con 200 mg de EPA+DHA/kg/día, c) dieta alta en grasa (20% proteína, 20% hidratos de carbono, 60% lípidos), y d) dieta alta en grasas más EPA+DHA. Se evaluaron la esteatosis hepática (histología), resistencia a la insulina (HOMA), estrés oxidativo hepático (GSH/GSSG, proteínas carboniladas y 8-isoprostanos) y el contenido de ácidos grasos hepáticos. La disminución significativa en los parámetros hepáticos de estrés oxidativo (p <0,05, ANOVA seguido de Newman-Keuls) se correlacionó positivamente (test de Pearson) con el HOMA y los niveles de AGPI ω-3, junto con la hepatoprotección observada. Se concluye que la prevención de EHGNA por suplementación con EPA+DHA, se acompaña de una correlación inversa entre el estrés oxidativo y la resistencia a la insulina y la disminución de AGPI ω-3 hepáticos.

Bioconversion of α-linolenic acid to n-3 LCPUFA and expression of PPAR-alpha, acyl Coenzyme A oxidase 1 and carnitine acyl transferase I are incremented after feeding rats with α-linolenic acid-rich oils.

High dietary intake of n-6 fatty acids in relation to n-3 fatty acids may generate health disorders, such as cardiovascular and other chronic diseases. Fish consumption rich in n-3 fatty acids is low in Latin America, it being necessary to seek other alternatives to provide α-linolenic acid (ALA), precursor of n-3 LCPUFA (EPA and DHA). Two innovative oils were assayed, chia (Salvia hispanica) and rosa mosqueta (Rosa rubiginosa). This study evaluated hepatic bioconversion of ALA to EPA and DHA, expression of PPAR-α, acyl-Coenzyme A oxidase 1 (ACOX1) and carnitine acyltransferase I (CAT-I), and accumulation of EPA and DHA in plasma and adipose tissue in Sprague-Dawley rats. Three experimental groups were fed 21 days: sunflower oil (SFO, control); chia oil (CO); rosa mosqueta oil (RMO). Fatty acid composition of total lipids and phospholipids from plasma, hepatic and adipose tissue was assessed by gas-liquid chromatography and TLC. Expression of PPAR-α (RT-PCR) and ACOX1 and CAT-I (Western blot). CO and RMO increased plasma, hepatic and adipose tissue levels of ALA, EPA and DHA and decreased n-6:n-3 ratio compared to SFO (p < 0.05, One-way ANOVA and Newman-Keuls test). CO increased levels of ALA and EPA compared to RMO (p < 0.05). No significant differences were observed for DHA levels. CO also increased the expression of PPAR-α, ACOX1 and CAT-I. Only CAT-I levels were increased by RO. CO and RMO may be a nutritional alternative to provide ALA for its bioconversion to EPA and DHA, and to increase the expression of PPAR-α, ACOX1 and CAT-I, especially CO-oil.