Direct Antioxidant Research Articles

MOMAST® Reduces the Plasmatic Lipid Profile and Oxidative Stress and Regulates Cholesterol Metabolism in a Hypercholesterolemic Mouse Model: The Proof of Concept of a Sustainable and Innovative Antioxidant and Hypocholesterolemic Ingredient.

MOMAST® is a patented natural phenolic complex, rich in tyrosol (9.0 g/kg, Tyr), hydroxityrosol (43,5 g/kg, OH-Tyr), and verbascoside (5.0 g/Kg), which is obtained from the OVW by-product of the Coratina cultivar with potent direct antioxidant activity (measured by DPPH and FRAP assays, respectively). Indeed, MOMAST® represents an innovative sustainable bioactive ingredient which has been obtained with ethical and empowering behavior by applying the principles of a circular economy. In the framework of research aimed at fostering its health-promoting activity, in this study it was clearly demonstrated that MOMAST® treatment reduced the oxidative stress and levels of total cholesterol (TC) and low-density lipoprotein (LDL) cholesterol, and increased the HDL levels, without changes in the triglyceride (TG) levels in Western diet (WD)-fed mice. The modulation of the plasmatic lipid profile is similar to red yeast rice (RYR) containing Monacolin K (3%). In addition, at the molecular level in liver homogenates, similarly to RYR, MOMAST® exerts cholesterol-lowering activity through the activation of LDL receptor, whereas, unlike RYR, MOMAST® reduces proprotein convertase subtilisin/kexin type 9 (PCSK9) protein levels via hepatic nuclear factor 1 (HNF1)-α activation. Hence, this study provides the proof of concept regarding the hypocholesterolemic activity of MOMAST, which could be successfully exploited as an active ingredient for the development of innovative and sustainable dietary supplements and functional foods.

COMPARATIVE EFFECT OF ATENOLOL AND NEBIVOLOL ON REVERSE REMODELING OF INTRAMURAL CORONARY ARTERIOLES IN THE SPONTANEOUSLY HYPERTENSIVE RAT MODEL

Objective: Arterial hypertension is an established major risk factor for ischemic heart disease. Functional and structural abnormalities at the level of the microcirculation may play a crucial role in coronary microvascular dysfunction. Indeed, coronary flow reserve is often reduced at angiography in hypertensive patients independently on the presence of left ventricular hypertrophy (Mancini M. et al. Microcirculation 2017). The aim of this study was to assess the effect of the beta-blocker Atenolol and the selective third-generation beta1-adrenergic antagonist Nebivolol on markers of remodeling and endothelial dysfunction in coronary microvascular. Nebivolol has been demonstrated to possess direct vasodilator and antioxidant properties which may improve endothelial dysfunction and reduce smooth muscle cell proliferation. Design and method: For this purpose, we used three groups of SHR rats: Hypertensive untreated group (SHR); SHR plus Atenolol 50 mg/kg/day by oral gavaging for 8 weeks (SHR + ATE); SHR plus Nebivolol 20 mg/kg/day by oral gavaging for 8 weeks (SHR + NEB). Protein expression levels of vasoactive factors, oxidative stress and remodeling markers in coronary microcirculation were determined by immunohistochemical analysis of Endothelin-1 (ET-1), inducible nitric oxide synthase (iNOS) and transforming growth factor-beta1 (TGF-beta1). Results: No differences were observed in structural parameters of mesenteric arteries among groups. SHR + NEB showed a significant reduction in ET-1, iNOS, and TGF-beta1 staining in coronary small arteries comparing to SHR and SHR + ATE. Conclusions: In comparison to atenolol, nebivolol may provide additional benefit beyond blood pressure reduction and beta-receptor blockade since show greater activity in the modulation of protein involved in vasodilation and oxidative stress protection.

A comparative study of metabolites profiles, anti-inflammatory and antioxidant activity of methanolic extracts from three Arthrospira strains in RAW 264.7 macrophages

Arthrospira (spirulina), is a cyanobacterium endowed with antioxidant and anti-inflammatory activity, but strain-dependent production of bioactive compounds may impact these properties. In LPS-stimulated RAW 264.7 macrophages, we compared the antioxidant and anti-inflammatory activity of methanolic extracts from two A. platensis (F&M-C256 and F&M-C260), and an A. maxima (F&M-C258) strains. F&M-C260 (5–25 μg/mL) concentration dependently inhibited LPS-induced NO release (p < 0.01) while F&M-C256 was effective only at the highest concentration (p < 0.01) and F&M-C258 had no activity. Both A. platensis strains significantly suppressed iNOS and COX-2 expression and PGE2 production, while A. maxima lacked effects. Only F&M-C260 up-regulated miR-223 expression (p < 0.001). A. maxima showed the highest inhibition of NLRP3 and IL1-β expression (p < 0.001) and IL1-β secretion (p < 0.01). All extracts displayed direct antioxidant activity and counteracted LPS-induced SOD2 overexpression without affecting HO-1 expression. Metabolites profiles, explored by HPLC-UV and HPLC-HRMS, revealed that F&M-C260 and F&M-C256 were the richest in β-cryptoxanthin and monogalactosyl monoglycerides respectively, with minor differences in zeaxanthin and β-carotene content.These results suggest that the antioxidant activity of the extracts was due to a direct reducing effect rather than to the transcriptional activation of SOD2 and HO-1 and that their differential and multitarget anti-inflammatory effects were correlated to differences in metabolites profiles.

Antioxidant Effect Assessment and Trans Epithelial Analysis of New Hempseed Protein Hydrolysates.

Hempseed (Cannabis sativa) is one of the most promising sources of plant proteins. It contains approximately 24% (w/w) protein, and edestin accounts for approximately 60-80% (w/w) of its total proteins. In a framework of research aimed at fostering the proteins recovered from the press cake by-products generated after the extraction of hempseed oil, two hempseed protein hydrolysates (HH1 and HH2) were produced at an industrial level using a mixture of different enzymes from Aspergillus niger, Aspergillus oryzae, and Bacillus licheniformis for different times (5 h and 18 h). Using a combination of different direct antioxidant tests (DPPH, TEAC, FRAP, and ORAC assays, respectively), it has been demonstrated that HHs exert potent, direct antioxidant activity. A crucial feature of bioactive peptides is their intestinal bioavailability; for this reason, in order to solve this peculiar issue, the ability of HH peptides to be transported by differentiated human intestinal Caco-2 cells has been evaluated. Notably, by using mass spectrometry analysis (HPLC Chip ESI-MS/MS), the stable peptides transported by intestinal cells have been identified, and dedicated experiments confirmed that the trans-epithelial transported HH peptide mixtures retain their antioxidant activity, suggesting that these hempseed hydrolysates may be considered sustainable antioxidant ingredients to be exploited for further application, i.e., nutraceutical and/or food industries.

Sulforaphane Attenuates Neutrophil ROS Production, MPO Degranulation and Phagocytosis, but Does Not Affect NET Formation Ex Vivo and In Vitro.

Sulforaphane has several effects on the human body, including anti-inflammation, antioxidation, antimicrobial and anti-obesity effects. In this study, we examined the effect of sulforaphane on several neutrophil functions: reactive oxygen species (ROS) production, degranulation, phagocytosis, and neutrophil extracellular trap (NET) formation. We also examined the direct antioxidant effect of sulforaphane. First, we measured neutrophil ROS production induced by zymosan in whole blood in the presence of 0 to 560 µM sulforaphane. Second, we examined the direct antioxidant activity of sulforaphane using a HOCl removal test. In addition, inflammation-related proteins, including an azurophilic granule component, were measured by collecting supernatants following ROS measurements. Finally, neutrophils were isolated from blood, and phagocytosis and NET formation were measured. Sulforaphane reduced neutrophil ROS production in a concentration-dependent manner. The ability of sulforaphane to remove HOCl is stronger than that of ascorbic acid. Sulforaphane at 280 µM significantly reduced the release of myeloperoxidase from azurophilic granules, as well as that of the inflammatory cytokines TNF-α and IL-6. Sulforaphane also suppressed phagocytosis but did not affect NET formation. These results suggest that sulforaphane attenuates neutrophil ROS production, degranulation, and phagocytosis, but does not affect NET formation. Moreover, sulforaphane directly removes ROS, including HOCl.

Normal or parallel configuration in spectroelectrochemistry? Bidimensional spectroelectroanalysis in presence of an antioxidant compound

This work demonstrates how the way a chemical system is sampled plays a key role in spectroelectroanalysis, illustrated by the quantification of an analyte in presence of an antioxidant compound. For this purpose, bidimensional spectroelectrochemistry experiments were performed using epinephrine as the model analyte and ascorbic acid as antioxidant and interfering compound, as a proof of concept. This is the first time that three calibration curves are obtained simultaneously on a single spectroelectrochemistry data set, one for the electrochemical signal and two for the optical responses in normal and parallel configurations. The differences between the two optical arrangements, that are related to the diffusion process which is an essential feature for the spectroelectrochemical detection of compounds, have been experimentally demonstrated. As can be observed, the spectral signal in parallel configuration allows us to obtain the best analytical results, since in this configuration only the first micrometers of the solution adjacent to the electrode surface are sampled, thus removing the interfering effect of the antioxidant compound. This fact does not occur with either the electrochemical signal or the spectral response in normal configuration. Furthermore, it has been shown that the parallel configuration provides better results than the normal configuration in terms of sensitivity. In summary, epinephrine is successfully detected in a simple and effective way, even in the presence of a direct antioxidant compound such as ascorbic acid at different concentrations levels, which makes spectroelectrochemistry a good choice for quantitative analysis.

Evaluation of the Antioxidant Activity of Levetiracetam in a Temporal Lobe Epilepsy Model.

Epilepsy is a neurological disorder in which it has been shown that the presence of oxidative stress (OS) is implicated in epileptogenesis. The literature has shown that some antiseizure drugs (ASD) have neuroprotective properties. Levetiracetam (LEV) is a drug commonly used as an ASD, and in some studies, it has been found to possess antioxidant properties. Because the antioxidant effects of LEV have not been demonstrated in the chronic phase of epilepsy, the objective of this study was to evaluate, for the first time, the effects of LEV on the oxidant-antioxidant status in the hippocampus of rats with temporal lobe epilepsy (TLE). The in vitro scavenging capacity of LEV was evaluated. LEV administration in rats with TLE significantly increased superoxide dismutase (SOD) activity, increased catalase (CAT) activity, but did not change glutathione peroxidase (GPx) activity, and significantly decreased glutathione reductase (GR) activity in comparison with epileptic rats. LEV administration in rats with TLE significantly reduced hydrogen peroxide (H2O2) levels but did not change lipoperoxidation and carbonylated protein levels in comparison with epileptic rats. In addition, LEV showed in vitro scavenging activity against hydroxyl radical (HO•). LEV showed significant antioxidant effects in relation to restoring the redox balance in the hippocampus of rats with TLE. In vitro, LEV demonstrated direct antioxidant activity against HO•.

Valorization of the Antioxidant Effect of Mantua PGI Pear By-Product Extracts: Preparation, Analysis and Biological Investigation.

For improving the management of the production chain of PGI Mantua pears (which comprises many varieties, including Abate Fetel), applying the cardinal principles of circular economy and sustainability, the fruits with diseases or defects were recovered for producing dried rounds of pears from the Abate Fetel cultivar, a new product with high nutritional value that extends the remaining life. This process led to the production of secondary and residual by-products, which are mainly composed of the highest and lowest part of the fruits, comprising seeds, pulps, peels and petioles. Hence, this study was focused on the valorization of these secondary by-products of Abate Fetel pears through the production of pear extracts using traditional and "green" extraction methods that involve the use of supercritical CO2 fluid extraction. The produced extracts, together with a reference solvent-derived extract, were analyzed by HPLC-ESI-MS, and in parallel, their direct and cellular antioxidant activity were assessed. Evidence has indicated that all the tested extracts reduced the H2O2-induced reactive oxygen species (ROS), lipid peroxidation and nitric oxide (NO) levels, respectively, in human intestinal Caco-2 cells. Hence, this study clearly suggests that extracts obtained from Mantuan PGI pear by-products may be used as valuable sources of bioactive upcycled phytocomplex for the development of dietary supplements and/or functional foods.

Newly Synthesized Creatine Derivatives as Potential Neuroprotective and Antioxidant Agents on In Vitro Models of Parkinson's Disease.

Oxidative stress is one of the key factors responsible for many diseases-neurodegenerative (Parkinson and Alzheimer) diseases, diabetes, atherosclerosis, etc. Creatine, a natural amino acid derivative, is capable of exerting mild, direct antioxidant activity in cultured mammalian cells acutely injured with an array of different reactive oxygen species (ROS) generating compounds. The aim of the study was in vitro (on isolated rat brain sub-cellular fractions-synaptosomes, mitochondria and microsomes) evaluation of newly synthetized creatine derivatives for possible antioxidant and neuroprotective activity. The synaptosomes and mitochondria were obtained by multiple centrifugations with Percoll, while microsomes-only by multiple centrifugations. Varying models of oxidative stress were used to study the possible antioxidant and neuroprotective effects of the respective compounds: on synaptosomes-6-hydroxydopamine; on mitochondria-tert-butyl hydroperoxide; and on microsomes-iron/ascorbate (non-enzyme-induced lipid peroxidation). Administered alone, creatine derivatives and creatine (at concentration 38 µM) revealed neurotoxic and pro-oxidant effects on isolated rat brain subcellular fractions (synaptosomes, mitochondria and microsomes). In models of 6-hydroxydopamine (on synaptosomes), tert-butyl hydroperoxide (on mitochondria) and iron/ascorbate (on microsomes)-induced oxidative stress, the derivatives showed neuroprotective and antioxidant effects. These effects may be due to the preservation of the reduced glutathione level, ROS scavenging and membranes' stabilizers against free radicals. Thus, they play a role in the antioxidative defense system and have a promising potential as therapeutic neuroprotective agents for the treatment of neurodegenerative disorders, connected with oxidative stress, such as Parkinson's disease.

Effects of Chokeberries (Aronia spp.) on Cytoprotective and Cardiometabolic Markers and Semen Quality in 109 Mildly Hypercholesterolemic Danish Men: A Prospective, Double-Blinded, Randomized, Crossover Trial.

Background: Chokeberries (Aronia spp.) are known to exhibit both direct and indirect antioxidant properties and have been associated with beneficial effects on human health, including cardiovascular risk factors (inflammation, serum lipids, sugars, blood pressure), oxidative stress, and semen quality. This prospective, double-blinded, randomized, crossover clinical trial was conducted to elucidate the effects of Aronia supplementation on these health targets in mildly hypercholesterolemic men. Methods: The standardized Aronia supplementation comprised three wild Aronia spp. (A. arbutifolia, A prunifolia and A. melanocarpa) and the Aronia hybrid × Sorbaronia mitschurinii (standardized to 150 mg anthocyanins daily). Participants (n = 109) were healthy men with respect to all outcome targets except for the total cholesterol level (5.0−7.0 mM). Participants were randomized to supplementation with either Aronia or placebo for 90 days, followed by a wash-out period and lastly the complementary supplementation. Effects on the health parameters were compared among both the whole group of men and in subgroups according to age, body mass index (BMI), lifestyle, dietary habits, and serum glutathione levels at baseline. The study is registered in ClinicalTrials.gov.: NCT03405753. Results: Glutathione levels were significantly improved after 90 days intake of Aronia supplementation compared to placebo in the subgroup of men with a low level of glutathione at baseline (p = 0.038) and a high coffee intake (p = 0.045). A significant decrease in levels of sperm DNA fragmentation and an increase in the percentage of motile sperm were observed in men aged >40 and in men with BMI > 25. Further, these parameters were significantly improved in the dietary subgroup defined by a high level of coffee intake. Total cholesterol and low-density lipoprotein-cholesterol levels decreased significantly in men <40 years after Aronia supplementation. No statistically significant effects were observed regarding blood pressure, markers of blood sugar regulation, hemoglobin A1c, superoxide dismutase, catalase, isoprostane levels, high sensitivity C reactive protein, or other semen parameters. Conclusions: This study demonstrated a significant increase in glutathione levels and improvement of cytoprotective targets following Aronia supplementation in specific subgroups of men >40 years of age and BMI > 25 but did not demonstrate a significant effect in the overall analysis. The observed concurrent increase in glutathione levels and improvement of cytoprotective targets following Aronia supplementation in subgroups of men, suggests that the endogenous phase II antioxidant glutathione is involved in the modulation of the observed cytoprotective effects. This study is a good foundation for further investigation of these cytoprotective effects in groups with oxidative stress in a dose−response study.

Sports nutrition supplements: Current dental perspective

Introduction: Despite their frequent consumption, studies on oral cavity effects of sports supplements that have shown a positive effect on health or performance are scarce. Methodology: Current literature review in the dental, medical and public health fields was carried out using the following databases: Pubmed, MedLine and Biblioteca UANL. Whey protein, creatine, magnesium and beta alanine were used from which those framed in the dates 2017-2022 were selected. Results: Whey protein: When interacting with salivary proteins, they remove the lubricating saliva layer of the mouth and can directly influence the epithelial tissue; in acidic conditions they exhibit astringency which is perceived as increased oral friction or roughness. Creatine: Exhibits non-energy related properties, contributing as a possible direct and indirect antioxidant and eliciting anti-inflammatory effects. Magnesium: In the oral cavity, low dietary intake of magnesium or deficiency is associated with the prevalence of periodontitis. Beta Alanine: The only reported side effect is paresthesia, this can be attenuated by using lower divided doses (1.6 g) or by using a sustained release formulation. Conclusion: It is important to investigate in the initial questioning of patients in the dental office about the possible use of sports nutrition supplements, since some of them could have repercussions on systemic and oral health. Its use should be taken hand in hand with a specialist since the recommended doses could vary depending on age, gender, requirement and general condition.

Dijetarni antioksidansi i zdravstveni efekti - koliki je optimalan unos?

A well-balanced diet provides many compounds with antioxidant properties, such as vitamins, minerals, provitamins (e.g., b-carotene), and phytochemicals (e.g., carotenoids, polyphenols, organosulfur compounds). In addition to direct antioxidants, foods indirectly support the endogenous defense system, by providing substrates for the synthesis of glutathione, antioxidant defense enzymes, metal-binding proteins, or modulators of redox-dependent signaling pathways. Epidemiological studies indicate that higher intakes and circulating concentrations of vitamins C, E, carotenoids, and flavonoids reflect a lower risk of chronic diseases and all-cause mortality, suggesting the importance of optimal intakes of these substances. However, unlike antioxidant micronutrients, phytochemicals have no defined recommended intake levels. A diet should be based on consuming various plant foods (fruit, vegetables, legumes, whole grains, seeds, nuts), antioxidant-rich beverages, and a moderate intake of animal food products to fully exploit the health-promoting effects of dietary antioxidants.

Targeting Mitochondria and Oxidative Stress in Cancer- and Chemotherapy-Induced Muscle Wasting.

Significance: Cancer is frequently associated with the early appearance of cachexia, a multifactorial wasting syndrome. If not present at diagnosis, cachexia develops either as a result of tumor progression or as a side effect of anticancer treatments, especially of standard chemotherapy, eventually representing the direct cause of death in up to one-third of all cancer patients. Cachexia, within its multiorgan affection, is characterized by severe loss of muscle mass and function, representing the most relevant subject of preclinical and clinical investigation. Recent Advances: The pathogenesis of muscle wasting in cancer- and chemotherapy-induced cachexia is complex, and encompasses heightened protein catabolism and reduced anabolism, disrupted mitochondria and energy metabolism, and even neuromuscular junction dismantling. The mechanisms underlying these alterations are still controversial, especially concerning the molecular drivers that could be targeted for anticachexia therapies. Inflammation and mitochondrial oxidative stress are among the principal candidates; the latter being extensively discussed in the present review. Critical Issues: Several approaches have been tested to modulate the redox homeostasis in tumor hosts, and to counteract cancer- and chemotherapy-induced muscle wasting, from exercise training to distinct classes of direct or indirect antioxidants. We herein report the most relevant results obtained from both preclinical and clinical trials. Future Directions: Including the assessment and the treatment of altered redox balance in the clinical management of cancer patients is still a big challenge. The available evidence suggests that fortifying the antioxidant defenses by either pharmacological or nonpharmacological strategies will likely improve cachexia and eventually the outcome of a broad cancer patient population. Antioxid. Redox Signal. 38, 352-370.

Use and Applicability of Ozone Therapy in Clinical Practice in Dentistry: An Integrative Review

Ozone is a colorless gas with a characteristic odor present in nature in the form of trivalent oxygen. In 2015, the Federal Council of Dentistry (CFO/Brazil) approved the use of ozone therapy and in 2018 the Ministry of Health (MS/Brazil) approved the application of Ozone Therapy as a Complementary Integrative Practice in the Unified Health System. Therefore, the objective of this study was to verify the applicability of ozone therapy in dental practice. This is an integrative literature review whose search was performed in the Medline/Pubmed, LILACS, SciElo, and Google Scholar databases. Studies published in the last 5 years in English, Portuguese or Spanish were eligible. After the search, 312 titles were found and after exclusion of duplicates and analysis of abstracts and full text, 13 articles were included in this review. The literature reports the application of ozone therapy in several areas in the treatment of acute and chronic diseases. As a mechanism of action, ozone has a direct antimicrobial effect, immunoregulation, antioxidant defenses, analgesic, and vasodilator effects. In dentistry, its applicability is mainly in preventive dentistry and as a complement in surgical procedur es, endodontic, and periodontal treatments.

МИТОХОНДРИАЛЬНО-НАПРАВЛЕННЫЙ АНТИОКСИДАНТ SKQ1 РЕГУЛИРУЕТ СИГНАЛЬНУЮ СИСТЕМУ KEAP1/NRF2/ARE И АПОПТОЗ В ЛЕЙКОЦИТАХ КРОВИ ПРИ ОКИСЛИТЕЛЬНОМ СТРЕССЕ

This study demonstrated that hyperoxia induced (0.5 MPa, 90 min) oxidative stress decreased mRNA level of Nrf2 transcription factor and Nrf2 induced genes encoding antioxidant enzymes (SOD1, CAT, GPx4) in leukocytes of rat blood. The change in gene expression profiles in hyperoxia was accompanied by disbalance of antioxidant enzyme activities in the leukocytes – activation of superoxide dismutase, and inhibition of catalase, glutathione peroxidase. The administration of SkQ1 (50 nmol/kg during 5 days) significantly increased mRNA level of Nrf2 transcription factor and Nrf2 induced genes encoding antioxidant enzymes SOD2 and GPx4 and nor malized the transcriptional activity of the SOD1 and CAT genes in the leukocytes under the hyperoxia induced oxidative stress. Catalase and glutathione peroxidase activity in the leukocytes increased concurrently with reversion of superoxide dismutase activity to the control level. The protective effect of SkQ1 in hyperoxia induced oxidative stress may be realized via direct antioxidant activity and the stimulation of the Keap1/Nrf2/ARE defense system. Administration of SkQ1 in extremely low amounts (50 nmol/kg for 5 days) effectively inhibits the accumulation of lipid peroxidation molecular products, normalizes the structural state of lymphocyte membranes and the level of their apoptosis under the condition of physiological standard and oxidative stress.

Effect of exercise-based cardiac rehabilitation on the ischemic threshold in patients with high-risk ischemic heart disease

Abstract Introduction Coronary artery disease is a complex condition and is not always resolved after an interventional or surgical procedure, due to the remaining obstructions in the coronary tree or the severity of the atherosclerosis, leaving anginal symptoms, ischemic threshold (IU) in the exercise, decreased cardiorespiratory fitness, and poor quality of life (QoL). Exercise-based cardiac rehabilitation programs (Ex-CRP) usually develop ischemic preconditioning mechanisms thanks to their direct anti-inflammatory, antioxidant, antithrombotic and coronary neovascularization effects, thus improving coronary reserve flow. We hypothesize that an Ex-CRP is capable of favorably impacting the UI in these patients. Therefore, the objective of this study is to evaluate the effects of an Ex-CRP on the UI in patients with high-risk ischemic heart disease. Methods Quasi-experimental study with 121 patients with ischemic threshold due to high-risk ischemic heart disease (with perfusion defects in nuclear medicine, complex coronary anatomy or partially revascularized) and presence of ischemic threshold in the exercise test. An Ex-CRP of 4–6 weeks duration was performed, consisting of supervised and monitored training concurrent with 30-minute aerobic exercise sessions at 70% of heart rate reserve, 3 times per week, supplemented with resistance exercise. and an educational understanding program for the control of risk factors and nutritional and psycho-emotional care. At the end of the program, a stress test was performed to compare the post-intervention effects and ischemic threshold was defined as the presence of angina or electrocardiographic changes of ischemia with negative ST-segment depression in 2 consecutive beats more than 80 ms from the J point. and in more than two contiguous leads. Results The 121 patients with ischemic threshold were 61±10 years old and 75% were male. On the other hand, 29.7% had a diagnosis of heart failure and an average LVEF of 53.1±12.9%. After Ex-CRP, an improvement was found in calculated VO2p (24.7±7.8 vs 34.23±7.5; p=0.000), METs at maximum effort from 7.06±2.15 to 9.78±1.14 (p&amp;lt;0.0001) and submaximal load in watts from 44±21.32 to 61±24.49; p&amp;lt;0.0001. 40.5% of the patients who were admitted with UI resolved it (absence of post-intervention ischemic diagnosis) after Ex-CRP and the remaining percentage with UI (59.5%) displaced it by 2.62 METs (p&amp;lt;0.0001). With this, the cardiovascular risk calculated by the Duke Score also decreased from −7 to −2 (p&amp;lt;0.0001), and the myocardial efficiency index improved from 8 to 6 (p&amp;lt;0.0001), strength (79±15 to 92±8%; p&amp;lt;0.0001) and QoL (65±17 vs 82±12; p&amp;lt;0.0001). Conclusions Ex-CRP had a significant effect on the resolution or displacement of the UI in patients with high-risk ischemic heart disease. In addition, it improved muscle strength, quality of life, myocardial efficiency, and reduced the cardiovascular risk index calculated by the Duke score. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Centro de Estudios e Investigaciόn FISICOL. Cúcuta, ColombiaCardioFit. CDMX, México

Myo-inositol in the treatment of male factor infertility

About 187 million couples worldwide suffer from infertility, with the male factor being diagnosed in 2070% of cases. The main cause of idiopathic infertility has been recognized as the adverse effects of reactive oxygen species. On the one hand, the cellular antioxidant defense is a highly efficient multilevel system; therefore, the pharmacological targets may vary. On the other hand, antioxidant enzymes (superoxide dismutase, catalase, peroxidase) have high activity and specificity, which limits the pharmacological capabilities of direct antioxidants. Indirect methods, such as the normalization of mitochondrial function, are more promising. Mitochondria play a key role in providing energy for sperm motility (one of the main factors of male fertility). Myo-inositol (MI) derivatives involved in cell signaling regulate intracellular Ca2+ ion levels affecting mitochondrial oxidative metabolism and adenosine triphosphate production. Thus, mitochondrial antioxidants are of particular interest for therapeutic strategies. Currently, various routes and regimens of MI use in the treatment of males with oligo-astheno-teratozoospermia (OAT) are being considered in clinical practice. MI-based oral nutraceutical complexes for the treatment of male factor infertility contain both direct and indirect antioxidants. In vitro studies revealed damage to mitochondrial cristae in the sperm intermediate tract in patients with OAT. Experimental studies have demonstrated that mitochondrial structure is restored when sperm are incubated in an MI-containing medium. Clinical studies confirmed that sperm incubation in such an environment leads to increased sperm motility and viability in patients with OAT. Intravaginal administration of MI showed increased total sperm motility and an increased proportion of progressively motile sperm. It is the progressive motility that is considered the best marker for identifying quality and healthy sperm. This type of sperm is usually used for in vitro fertilization techniques. In addition, intravaginal MI administration improved the quality of cervical mucus and reduced its viscosity and crystallization. The effect of intravaginal MI on cervical mucus can be considered as an additional independent factor in increasing fertility.

Antioxidant and Anti-Inflammatory Actions of Polyphenols from Red and White Grape Pomace in Ischemic Heart Diseases.

Grape pomace (GP) represents a very reliable source of polyphenols because it could be found globally as a remnant of the wine industry. During the winemaking process, two types of GP are generated: red GP and white GP, according to the produced wine, red or white. Grape pomace represents a viable source of polyphenols, mainly flavanols, procyanidins anthocyanins, and resveratrol which possess antioxidant and anti-inflammatory activities. Multiple differences were observed between red and white GP in terms of their antioxidant and anti-inflammatory activity in both in vitro and in vivo studies. Although most studies are focused on the antioxidant and anti-inflammatory effect of red grape pomace, there are still many variables that need to be taken into consideration, as well as extensive study of the white GP. It was observed that in both in vitro and in vivo studies, the GP polyphenols have a direct antioxidant activity by acting as a free radical scavenger or donating a hydrogen atom. It also possesses an indirect antioxidant and anti-inflammatory activity by reducing mitochondrial reactive oxygen species (ROS) generation, malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α), interleukin-1-beta (IL-1β), interleukin-6 (IL-6), nuclear factor kappa-light-chain-enhancer of activated B cells (NF- κβ), and inhibitor of nuclear factor kappa-B kinase subunit beta (Iκκβ) levels or nitrate oxide-4 (NOX4) expression and by increasing the levels of antioxidants enzymes like superoxide dismutase (SOD), catalase (CAT) glutathione reductase (GRx) and glutathione peroxidase(GPx). Besides these activities, many beneficial effects in ischemic heart diseases were also observed, such as the maintenance of the ventricular function as close as possible to normal, and the prevention of infarcted area extension. In this context, this review intends to present the actual knowledge of grape pomace’s potential antioxidant and anti-inflammatory activity in ischemic heart disease, knowledge gathered from existing in vitro and in vivo studies focused on this.

N-acetylcysteine as a therapeutic approach to post-COVID-19 pulmonary fibrosis adjunctive treatment.

Growing interest is directed to the outcomes of COVID-19 in survivors, both in the convalescent period and in the long-term, which are responsible for morbidity and quality of life deterioration. This article aims to describe the mechanisms supporting the possible use of NAC as an adjuvant treatment for post-COVID-19 pulmonary fibrosis. A search was performed in PubMed/MEDLINE. Interstitial changes have been observed in the CT scan of COVID-19 pneumonia. In patients with respiratory outcomes in the post-COVID-19 stage, glutathione (GSH) deficiency was found and interpreted as a reaction to the inflammatory cascade caused by the viral infection, while the pathophysiological process of pulmonary fibrosis involves numerous cytokines, such as TGF-β, TNF-α, IL-1, PDGF and VEGF. NAC has a good tolerability profile, is easily administered orally and inexpensively, and has antioxidant and anti-inflammatory effects that may target the pathophysiologic mechanisms involved in pulmonary fibrosis. It may revert GSH deficiency, exerts direct and indirect antioxidant activity, anti-inflammatory activity and improves immune T-cell response. The mechanism of action of NAC suggests a role in the treatment of pulmonary fibrosis induced by COVID-19.

Comparative study of oral versus parenteral crocin in mitigating acrolein-induced lung injury in albino rats

Acrolein (Ac) is the second most commonly inhaled toxin, produced in smoke of fires, tobacco smoke, overheated oils, and fried foods; and usually associated with lung toxicity. Crocin (Cr) is a natural carotenoid with a direct antioxidant capacity. Yet, oral administration of crocin as a natural rout is doubtful, because of poor absorbability. Therefore, the current study aimed to compare the potential protective effect of oral versus intraperitoneal (ip) crocin in mitigating Ac-induced lung toxicity. 50 Adult rats were randomly divided into 5 equal groups; Control (oral-saline and ip-saline) group, Cr (oral-Cr and ip-Cr) group, Ac group, oral-Cr/Ac group, and ip-Cr/Ac group; for biochemical, histopathological, and immunohistochemical investigations. Results indicated increased oxidative stress and inflammatory biomarkers in lungs of Ac-treated group. Histopathological and immunohistochemical examinations revealed lung edema, infiltration, fibrosis, and altered expression of apoptotic and anti-apoptotic markers. Compared to oral-Cr/Ac group, the ip-Cr/Ac group demonstrated remarkable improvement in the oxidative, inflammatory, and apoptotic biomarkers, as well as the histopathological alterations. In conclusion, intraperitoneal crocin exerts a more protective effect on acrolein-induced lung toxicity than the orally administered crocin.