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Abstract Epilepsy, a widespread neural ailment considered by prolonged neuronal depolarization and repetitive discharge, has been linked to extreme stimulus of N-methyl-D-aspartate receptors (NMDARs). Despite the availability of approved anti-seizure medications (ASMs) in many developed nations, approximately 30% of epilepsy patients continue to experience drug-resistant seizures. Thus, a growing interest in discovering natural compounds as potential sources for new medications is growing. Sinapinic acid, a natural derivative of cinnamic acid found in food sources, is known for its neuroprotective properties. This study investigated how sinapinic acid interacts with NMDA receptors and its potential role in providing anticonvulsant effects. Male mice were randomly allocated into nine groups: a control group receiving normal saline (1 ml/kg), groups treated with sinapinic acid at doses of 1, 3, and 10 mg/kg, a group treated with diazepam at 10 mg/kg, a group treated with an NMDA agonist at 75 mg/kg, a group treated with an NMDA antagonist at 0.5 mg/kg, a group receiving the ineffective dose of sinapinic acid (1 mg/kg) along with the NMDA antagonist, and a group receiving the effective dose of sinapinic acid (10 mg/kg) along with the NMDA agonist. Sinapinic acid and other treatments were administered intraperitoneally 30 min prior to inducing seizures with PTZ injection. Seizure onset time was recorded following PTZ injection. Blood and brain samples were collected after anesthesia to determine serum and brain nitrite levels. Real-time PCR assessed NMDAR gene expression in the prefrontal cortex (PFC). Data were analyzed using Prism software. The time seizures began was notably extended in groups treated with sinapinic acid at doses of 3 and 10 mg/kg compared to those treated with saline (P

Abstract Glutamatergic neurotransmission and oxidative stress are involved in the pathophysiology of seizures. Some anticonvulsants exert their effects through modulation of these pathways. Trigonelline (TRG) has been shown to possess various pharmacological effects like neuroprotection. Therefore, this study was performed to determine TRG’s anticonvulsant effects, focusing on its potential effects on N-methyl-D-aspartate (NMDA) receptors, a type of glutamate receptor, and oxidative stress state in the prefrontal cortex (PFC) in PTZ-induced seizure in mice. Seventy-two male mice were randomly divided into nine groups. The groups included mice that received normal saline, TRG at doses of 10, 50, and 100 mg/kg, diazepam, NMDA (an agonist), ketamine (an antagonist), the effective dose of TRG with NMDA, as well as sub-effective dose of TRG with ketamine, respectively. All agents were administrated intraperitoneally 60 min before induction of seizures by PTZ. Latency to seizure, total antioxidant capacity (TAC), and malondialdehyde (MDA) levels in serum and PFC were measured. Furthermore, the gene expression of NR2A and NR2B, subunits of NMDA receptors, was measured in the PFC. TRG administration increased the latency to seizure onset and enhanced TAC while reducing MDA levels in both the PFC and serum. TRG also decreased the gene expression of NR2B in the PFC. Unexpectedly, the findings revealed that the concurrent administration of ketamine amplified, whereas NMDA mitigated, the impact of TRG on latency to seizure. Furthermore, NMDA diminished the positive effects of TRG on antioxidant capacity and oxidative stress, while ketamine amplified these beneficial effects, indicating a complex interaction between TRG and NMDA receptor modulation. In the gene expression of NMDA receptors, results showed that ketamine significantly decreased the gene expression of NR2B when co-administrated with a sub-effective dose of TRG. It was found that, at least partially, the anticonvulsant effect of TRG in PTZ-induced seizures in male mice was mediated by the attenuation of glutamatergic neurotransmission as well as the reduction of oxidative stress.

Abstract Metabolic syndrome (MetS) is a common disorder involving a cluster of metabolic abnormalities, such as abdominal obesity, hypertension, dyslipidemia, insulin resistance, and atherogenic profile. MetS is characterized by an increase in oxidative stress and a chronic proinflammatory state, which are directly related to the development and progression of this pathology. It has been seen how a healthy lifestyle and good dietary practices are key to improving the different metabolic parameters and, therefore, play a fundamental role in reducing the risk of developing diabetes. The present review focuses on the research evidence related to the therapeutic properties of Lycium barbarum L. in MetS gathered in the last years. Several preclinical studies suggest that L. barbarum extracts are a good dietary supplement for the prevention of cardiovascular diseases in people with MetS. This compound has been used for years in traditional Chinese medicine for the treatment of atrophic gastritis, problems related to the lungs, kidneys, and liver, and as a supplement for eye health. In addition, different in vitro and in vivo studies have been carried out that support the properties attributed to metabolites derived from L. barbarum, such as polysaccharides that have been shown diverse biological activities. In conclusion, L. barbarum extracts have multiple benefits to increase general well‐being and immune function. However, there are a limited number of studies related to effect of L. barbarum in MetS, but they demonstrated effectiveness in the treatment of obesity, diabetes mellitus type 2, and prevention of diabetes mellitus type 2 complication.

Objective(s): Multiple sclerosis (MS) is a chronic disease of the central nervous system (CNS) and its cause is unknown. Several environmental and genetic factors may have roles in the pathogenesis of MS. The synthesis of solid lipid nanoparticles (SLNs) for ivermectin (IVM) loading was performed to increase its efficiency and bioavailability and evaluate its ability in improving the behavioral and histopathological changes induced by cuprizone (CPZ) in the male C57BL/6 mice. Materials and Methods: Four groups of 7 adult C57BL/6 mice including control (normal diet), CPZ, IVM, and nano-IVM groups were chosen. After synthesis of nano-ivermectin, demyelination was induced by adding 0.2% CPZ to animal feed for 6 weeks. IVM and nano-IVM (1 mg/kg/day, IP) were given for the final 14 days of the study. At last, behavioral tests, histochemical assays, and immunohistochemistry of TRPA1, NF-kB p65, and GFAP were done.Results: The time of immobility of mice in the IVM and nano-IVM groups was reduced compared to the CPZ group. Histopathological examination revealed demyelination in the CPZ group, which was ameliorated by IVM and nano-IVM administration. In IVM and nano-IVM groups corpus callosum levels of TRPA1, NF-kB p65, and GFAP were decreased compared to the CPZ group. In the IVM and nano-IVM groups, the levels of MBP were significantly higher than in the CPZ group. Conclusion: The results evidenced that IVM and nano-IVM administration is capable of reducing demyelination in mice.

Introduction Despite international efforts, the number of individuals struggling with obesity is still increasing. An important aspect of obesity prevention relates to identifying individuals at risk at early stage, allowing for timely risk stratification and initiation of countermeasures. However, obesity is complex and multifactorial by nature, and one isolated (bio)marker is unlikely to enable an optimal risk stratification and prognosis for the individual; rather, a combined set is required. Such a multicomponent interpretation would integrate biomarkers from various domains, such as classical markers (eg, anthropometrics, blood lipids), multiomics (eg, genetics, proteomics, metabolomics), lifestyle and behavioural attributes (eg, diet, physical activity, sleep patterns), psychological traits (mental health status such as depression) and additional host factors (eg, gut microbiota diversity), also by means of advanced interpretation tools such as machine learning. In this paper, we will present a protocol that will be employed for a scoping review that attempts to summarise and map the state-of-the-art in the area of multicomponent (bio)markers related to obesity, focusing on the usability and effectiveness of such biomarkers.Methods and analysis PubMed, Scopus, CINAHL and Embase databases will be searched using predefined key terms to identify peer-reviewed articles published in English until January 2024. Once downloaded into EndNote for deduplication, CADIMA will be employed to review and select abstracts and full-text articles in a two-step procedure, by two independent reviewers. Data extraction will then be carried out by several independent reviewers. Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews and Peer Review of Electronic Search Strategies guidelines will be followed. Combinations employing at least two biomarkers from different domains will be mapped and discussed.Ethics and dissemination Ethical approval is not required; data will rely on published articles. Findings will be published open access in an international peer-reviewed journal. This review will allow guiding future directions for research and public health strategies on obesity prevention, paving the way towards multicomponent interventions.

Abstract Cancer is a leading cause of death worldwide and involves an oxidative stress mechanism. The transcription factor Nrf2 has a crucial role in cytoprotective response against oxidative stress, including cancer growth and progression and therapy resistance. For this reason, inhibitors of Nrf2 are new targets to be studied. Traditional plant-based remedies rich in phytochemicals have been used against human cancers and phenolic compounds are known for their chemopreventive properties. This comprehensive review offers an updated review of the role of phenolic compounds as anticancer agents due to their action on Nrf2 inhibition. In addition, the role of naturally-occurring bioactive anticancer agents are covered in the clinical applications of polyphenols as Nrf2 inhibitors. Video Abstract

Metabolic-associated fatty liver disease (MAFLD) is the most common chronic liver disease observed in clinical practice worldwide. This disorder has been independently associated with an increased risk of developing chronic kidney disease (CKD). The aim of this study was to evaluate whether a 2-year intervention based on a Mediterranean diet (MedDiet) and physical activity focussed on reducing intrahepatic fat contents (IFC) was associated with a decreased risk of CKD. Forty adults (50% women) residing in Mallorca, aged 48 to 60 years, diagnosed with MAFLD were recruited. Participants were divided into two groups based on whether they improved IFC measured by nuclear magnetic resonance. Anthropometric and clinical parameters improved in responders, including reduced weight, body mass index (BMI), and waist circumference. Only responders showed improvements in lipid profile and liver enzymes. Haematological parameters showed favourable changes in both groups. Oxidative stress and inflammatory biomarkers differed between groups. Responders had lower plasma interleukine-18 (IL-18) levels, but higher erythrocyte malonaldehyde (MDA) levels. Non-responders showed increased erythrocyte catalase and superoxide dismutase activity. After 2 years, non-responders had higher serum creatinine, Modification of Diet in Renal Disease (MDRD), and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) levels, while responders showed reductions in these parameters together with uric acid and urine albumin-to-creatinine ratio (UACR). Positive correlations were found between changes in IFC and kidney injury biomarkers, including MDRD and serum creatinine levels. In conclusion, a healthy diet based on the Mediterranean dietary pattern and lifestyle promotes significant improvements in parameters related to cardiovascular, hepatic, and renal health.

With the advent of highly effective plant-based medications with few or no side effects, the use of phytomedicines against complex diseases such as cancer is becoming more widespread. The broadly recognized pentacyclic triterpenes known as boswellic acids (BAs) are derived from the oleogum resin, or frankincense, extracted from the plant species of the genus Boswellia. The frankincense mixture contains various BA types, each having a different potential and helping treat certain cancers. This review focuses on details regarding the traits of the BAs, their roles as anti-cancer agents, the mechanism underlying their activities, and the function of their semi-synthetic derivatives in managing and treating certain cancers. The review also explores the biological sources of BAs, how they are conserved, and how biotechnology might help preserve and improve in vitro BA production. The review concludes that the BAs and their semi-synthetic derivatives are effective against a broad spectrum of cancer cell lines. The detailed information in the review can be helpful for researchers to gain more information about BAs and BA-based medications for efficient and cost-effective cancer treatments.

Metabolic syndrome increases the risk of developing diabetes and cardiovascular disease. The regular practice of physical activity is a crucial factor for healthy aging and for controlling and preventing chronic diseases. To assess the effects of regular physical activity on the biochemical and inflammatory profiles, as well as the quality of life of older adults diagnosed with metabolic syndrome. Participants (aged 55–70 years; living in the Balearic Islands, Spain) were divided into two groups (n = 50 each) according to the degree of physical activity measured by metabolic equivalents of task (METs). Anthropometric parameters, blood pressure, biochemical and hematological parameters, and inflammatory biomarkers were measured. Beck Depression Inventory and adherence to the Mediterranean diet questionnaires, as well as the Dietary Inflammatory Index, chair test, health-related quality of life (HRQoL), and Rapid Assessment of Physical Activity, were also determined. The characterization of the patients was similar in both groups, showing a homogeneous sample. The group with the highest METs experienced a decrease in depression and an increase in the intensity of physical activity. Adherence to the Mediterranean diet and HRQoL physical dimensions increased in participants with the highest METs, also showing a decrease in glycemia and glycosylated hemoglobin values. Inflammatory biomarkers, including tumor necrosis factor alpha, interleukin-6, interleukin-1β, and osteoprotegerin, decreased in patients practicing more physical activity. High levels of physical activity are related to a healthier lifestyle, characterized by high adherence to the Mediterranean diet, decreased depressive behavior, oxidative stress, and inflammatory status in older people with metabolic syndrome.

Background: The Mediterranean Diet (MedDiet) is recognized as a healthy dietary pattern. Non-alcoholic fatty liver disease (NAFLD) is characterized by the excessive accumulation of fat in the liver. Objectives: To assess the antioxidant status in erythrocytes, plasma, and peripheral blood mononuclear cells (PBMCs) of NAFLD patients following a 24-month lifestyle intervention based on the MedDiet. Adult patients (n = 40; aged 40–60 years) diagnosed with NAFLD by magnetic resonance imaging were divided into two groups based on their adherence to the MedDiet. Consumption was assessed using a validated 143-item semiquantitative Food Frequency Questionnaire. Anthropometrics, biochemistry parameters, intrahepatic fat contents (IFC), antioxidants, and inflammatory biomarkers were measured in plasma and erythrocytes before and after the intervention. Results: After the intervention, body mass index (BMI) and plasma levels of total cholesterol, low-density lipoprotein cholesterol (LDL-chol), triglycerides, malondialdehyde (MDA), and cytokeratin-18 (CK18) decreased, and high-density lipoprotein cholesterol (HDL-chol) increased. Participants with high adherence to MedDiet showed lower IFC, hepatic enzyme (AST, ALT, and GGT), glycemia, oxidase LDL (oxLDL) plasma levels, and erythrocyte MDA levels. Higher antioxidant activity (erythrocyte catalase-CAT, superoxide dismutase-SOD, glutathione peroxidase-GPx, glutathione reductase-GRd, and total glutathione-GSH as well as PBMCs-CAT gene expression) was observed in these patients, along with a reduction of PBMCs reactive oxygen species production and Toll-like receptor 4 (TLR4) expression. Inverse associations were observed between adherence to the MedDiet and BMI, glycemia, AST, IFC, and CK18 plasma levels and oxLDL, CAT, SOD, and GRd activities in erythrocytes. A significant linear regression was observed between adherence to the MedDiet and antioxidant score. Conclusions: Adherence to the MedDiet is associated with improved plasma and PBMC antioxidant and inflammatory biomarker profiles and high antioxidant defences in erythrocytes.

Abstract The world population is progressively ageing, assuming an enormous social and health challenge. As the world ages, neurodegenerative diseases are on the rise. Regarding the progressive nature of these diseases, none of the neurodegenerative diseases are curable at date, and the existing treatments can only help relieve the symptoms or slow the progression. Recently, hormesis has increased attention in the treatment of age-related neurodegenerative diseases. The concept of hormesis refers to a biphasic dose-response phenomenon, where low levels of the drug or stress exert protective of beneficial effects and high doses deleterious or toxic effects. Neurohormesis, as the adaptive aspect of hormetic dose responses in neurons, has been shown to slow the onset of neurodegenerative diseases and reduce the damages caused by aging, stroke, and traumatic brain injury. Hormesis was also observed to modulate anxiety, stress, pain, and the severity of seizure. Thus, neurohormesis can be considered as a potentially innovative approach in the treatment of neurodegenerative and other neurologic disorders. Herbal medicinal products and supplements are often considered health resources with many applications. The hormesis phenomenon in medicinal plants is valuable and several studies have shown that hormetic mechanisms of bioactive compounds can prevent or ameliorate the neurodegenerative pathogenesis in animal models of Alzheimer’s and Parkinson’s diseases. Moreover, the hormesis activity of phytochemicals has been evaluated in other neurological disorders such as Autism and Huntington’s disease. In this review, the neurohormetic dose–response concept and the possible underlying neuroprotection mechanisms are discussed. Different neurohormetic phytochemicals used for the better management of neurodegenerative diseases, the rationale for using them, and the key findings of their studies are also reviewed.

Abstract Propolis, a resinous substance produced by honeybees from various plant sources, has been used for thousands of years in traditional medicine for several purposes all over the world. The precise composition of propolis varies according to plant source, seasons harvesting, geography, type of bee flora, climate changes, and honeybee species at the site of collection. This apiary product has broad clinical applications such as antioxidant, anti-inflammatory, antimicrobial, anticancer, analgesic, antidepressant, and anxiolytic as well asimmunomodulatory effects. It is also well known from traditional uses in treating purulent disorders, improving the wound healing, and alleviating many of the related discomforts. Even if its use was already widespread since ancient times, after the First and Second World War, it has grown even more as well as the studies to identify its chemical and pharmacological features, allowing to discriminate the qualities of propolis in terms of the chemical profile and relative biological activity based on the geographic place of origin. Recently, several in vitro and in vivo studies have been carried out and new insights into the pharmaceutical prospects of this bee product in the management of different disorders, have been highlighted. Specifically, the available literature confirms the efficacy of propolis and its bioactive compounds in the reduction of cancer progression, inhibition of bacterial and viral infections as well as mitigation of parasitic-related symptoms, paving the way to the use of propolis as an alternative approach to improve the human health. However, a more conscious use of propolis in terms of standardized extracts as well as new clinical studies are needed to substantiate these health claims.

Abstract Background In late 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which is responsible for coronavirus disease (COVID-19), was identified as the new pathogen to lead pneumonia in Wuhan, China, which has spread all over the world and developed into a pandemic. Despite the over 1 year of pandemic, due to the lack of an effective treatment plan, the morbidity and mortality of COVID-19 remains high. Efforts are underway to find the optimal management for this viral disease. Main body SARS-CoV-2 could simultaneously affect multiple organs with variable degrees of severity, from mild to critical disease. Overproduction of pro-inflammatory mediators, exacerbated cellular and humoral immune responses, and coagulopathy such as Pulmonary Intravascular Coagulopathy (PIC) contributes to cell injuries. Considering the pathophysiology of the disease and multiple microthrombi developments in COVID-19, thrombolytic medications seem to play a role in the management of the disease. Beyond the anticoagulation, the exact role of thrombolytic medications in the management of patients with COVID-19-associated acute respiratory distress syndrome (ARDS) is not explicit. This review focuses on current progress in underlying mechanisms of COVID-19-associated pulmonary intravascular coagulopathy, the historical use of thrombolytic drugs in the management of ARDS, and pharmacotherapy considerations of thrombolytic therapy, their possible benefits, and pitfalls in COVID-19-associated ARDS. Conclusions Inhaled or intravenous administration of thrombolytics appears to be a salvage therapy for severe ARDS associated with COVID-19 by prompt attenuation of lung injury. Considering the pathogenesis of COVID-19-related ARDS and mechanism of action of thrombolytic agents, thrombolytics appear attractive options in stable patients without contraindications.

Objective(s): Multiple Sclerosis (MS) is an inflammatory disorder wherein the myelin of nerve cells in the central nervous system is damaged. In the current study, we assessed the effect of Dapsone (DAP) on the improvement of behavioral dysfunction and preservation of myelin in the cuprizone (CPZ) induced demyelination model via targeting Nrf2 and IKB. Materials and Methods: MS was induced in C57BL/6 mice through diet supplementation of CPZ (0.2%) for 6 weeks, and DAP (12.5 mg/kg/day; IP) was administered for the last 2 weeks of treatment. Pole test and rotarod performance test, LFB and H&E staining, and Immunohistochemistry (IHC) staining of p-Nrf2 and p-IKB were performed. Furthermore, superoxide dismutase (SOD) and nitrite were measured.Results: DAP treatment prevented body loss induced by CPZ (P

In recent years, there has been an increase in the reporting of plastic pollution in the marine environment and its effects on marine animals, especially bony fish. However, the prevalence and effect, particularly concerning biomarkers of oxidative stress, in elasmobranchs remain underreported and unknown. In this study, microplastics were observed in two elasmobranch species from the Balearic Islands: the small-spotted catshark (Scyliorhinus canicula) with an average of 4.38 ± 1.77 items per individual, and the blackmouth catshark (Galeus melastomus) with an average of 8.31 ± 2.46 items per individual. Moreover, for the first time, antioxidant and pro-inflammatory responses were determined in the digestive tract of individuals of both species. Specifically, the activation of antioxidant defences, mainly superoxide dismutase activity and glutathione levels, was observed, while the pro-inflammatory marker myeloperoxidase activity was also greater in individuals with a high abundance of microplastic items. Additionally, a significant increase in glutathione S-transferase activity in catsharks with high microplastic ingestion was evidenced, suggesting that the detoxification process was activated. Overall, the results of this study highlight that both catshark species are ingesting microplastics, which, in turn, are causing physiological effects at a cellular level. Considering this, continued monitoring of these species should include the presence of microplastics, and the results from this study can serve as baseline data for future research.

Global change produces substantial modification to the distribution and rhythm of infection of diseases in fish, favouring the introduction of new pathogens. Recently, the presence of black spot disease, associated with a digenean fluke of the genus Scaphanocephalus, has been observed in specimens of Xyrichthys novacula on the island of Ibiza (Balearic Islands). The aim of the present study was to evaluate the antioxidant and immune response in both the skin mucus and spleen of X. novacula depending on the degree of infection by Scaphanocephalus sp. The specimens were captured in a control area, without the presence of the parasite, and in an affected area, classifying the fish as low infection (1–15 spots) and high infection (>15 spots). As the degree of infection increased, a decrease in the body condition index was observed. The activity of the antioxidant enzymes in the mucus—catalase, superoxide dismutase and glutathione peroxidase—increased progressively with the degree of infection. This activation of antioxidant defences was not enough to prevent an increase in malondialdehyde levels, an indicator of oxidative damage, in the group with the highest infection. Similarly, an increase in immunological parameters—lysozyme, alkaline phosphatase, myeloperoxidase and immunoglobulins—was observed in mucus as infection increased. Regarding the spleen, only an increase in lysozyme activity and alkaline phosphatase in fish with a greater severity of infection was observed. In conclusion, as the severity of Scaphanocephalus sp. infection increased, it induced an immune and oxidative stress response in skin mucus, leading to a decrease in overall body condition. The potential health effects that the ectoparasite may have on X. novacula populations will require follow-up studies.

Non-alcoholic fatty liver disease (NAFLD) is a complex and increasingly prevalent cardiometabolic disorder worldwide. As of today, NAFLD is a pathology without specific pharmacological treatment, with the Mediterranean diet (MedDiet) being the most widely used approach for its management. The objective of this study is to assess the effects of adherence to the Mediterranean diet on fatty acid plasma levels, as well as on the oxidative and inflammatory status of NAFLD patients. A total of 100 adult patients (40–60 years old) diagnosed with NAFLD and from the Balearic Islands, Spain, were classified into three groups according to their adherence to the MedDiet. Consumption was assessed using a validated 143-item semiquantitative Food Frequency Questionnaire. Food items (g/day) were categorised according to their processing using the NOVA system. Anthropometrics, blood pressure, aminotransferases, Dietary Inflammatory Index (DII), inflammatory biomarkers, and fatty acid levels were measured in the plasma of NAFLD patients. High adherence to the MedDiet is associated to a highly plant-based diet, low ultra-processed food (UPF) consumption, low intake of dietary lipids, low intake of animal fats, high intake of monounsaturated fatty acid (MUFA; mainly palmitoleic acid), low intake of saturated fatty acids (SFAs; practically all dietary SFAs), low intake of trans-fatty acids, high intake of omega-3 fatty acids (mainly eicosapentaenoic acid), a higher n-6:n-3 in ratio, low intake of omega-6 fatty acids, and a low level of interleukin-6 (IL-6). High adherence to the MedDiet is related to a better fatty acid profile in the plasma, fewer SFAs and more MUFA and polyunsaturated fatty acids (PUFAs), a plasma biochemical profile, better proinflammatory status, and decreased ultra-processed food consumption of NAFLD patients.

This study aimed to investigate the effects of diazinon on fish, focusing on hepatotoxic biomarkers and the potential protective effects of silymarin supplementation. One hundred eighty rainbow trout were randomly assigned to four groups: control, diazinon exposed (0.1 mg L−1), silymarin supplemented (400 mg kg−1), and diazinon + silymarin. Blood samples and liver tissue were collected after 7, 14, and 21 days of exposure to analyze biochemical parameters and oxidative biomarkers. Diazinon exposure in fish resulted in liver damage, as indicated by increased antioxidant enzyme activities in the hepatocytes. Silymarin showed the potential to mitigate this damage by reducing oxidative stress and restoring enzyme activities. Nevertheless, diazinon increased creatine phosphokinase activity, which may not be normalized by silymarin. Exposure to diazinon increased glucose, triglyceride, and cholesterol levels, whereas total protein, albumin, and globulin levels were significantly decreased in fish. However, silymarin controlled and maintained these levels within the normal range. Diazinon increased creatinine, urea, uric acid, and ammonia contents. Silymarin could regulate creatinine, urea, and uric acid levels while having limited effectiveness on ammonia excretion. Furthermore, diazinon increased malondialdehyde in hepatocytes, whereas administration of silymarin could restore normal malondialdehyde levels. Overall, silymarin showed potential as a therapeutic treatment for mitigating oxidative damage induced by diazinon in fish, but its effectiveness on creatine phosphokinase, glutathione reductase, and ammonia may be limited.

In the last few decades the consumption of ultra-processed foods (UPFs) worldwide has substantially augmented. Increasing evidence suggests that high UPF consumption is associated with an increase in non-communicable diseases, being overweight, and obesity. The aim of this study was to assess how UPF consumption affects oxidative and inflammatory status in the plasma, neutrophils, and urine of old adults with metabolic syndrome. Participants (n = 92) were classified into two groups according to UPF consumption. Dietary intakes were measured by a validated semi-quantitative 143-item food frequency questionnaire and UPF consumption was determined according to the NOVA classification system. Low UPF consumers showed higher adherence to the Mediterranean diet than high UPF consumers. A high intake of fiber and a high concentration of polyphenols in urine were also observed in subjects with low UPF consumption. Despite the absence of differences in biochemical profile, oxidative and inflammatory biomarkers showed some significant changes. Catalase and superoxide dismutase activities were lower in high UPF consumers, whereas myeloperoxidase activity was higher. ROS production in neutrophils stimulated with zymosan was higher in high UPF consumers than in low UPF consumers. Biomarkers such as xanthine oxidase, tumor necrosis factor α (TNFα), interleukin (IL)-6, IL-15, and leptin levels were higher in participants with high intake of UPF. No differences were found in malondialdehyde and other inflammatory cytokines. The current study evidenced that MetS participants with high UPF consumption have a more pro-oxidant and inflammatory profile than those with low UPF consumption, despite showing similar blood biochemical profiles.

Peroxisome proliferator-activated receptor γ (PPARγ) is a transcriptional coactivator that binds to a diverse range of transcription factors. PPARγ coactivator 1 (PGC-1) coactivators possess an extensive range of biological effects in different tissues, and play a key part in the regulation of the oxidative metabolism, consequently modulating the production of reactive oxygen species, autophagy, and mitochondrial biogenesis. Owing to these findings, a large body of studies, aiming to establish the role of PGC-1 in the neuromuscular system, has shown that PGC-1 could be a promising target for therapies targeting neuromuscular diseases. Among these, some evidence has shown that various signaling pathways linked to PGC-1α are deregulated in muscular dystrophy, leading to a reduced capacity for mitochondrial oxidative phosphorylation and increased reactive oxygen species (ROS) production. In the light of these results, any intervention aimed at activating PGC-1 could contribute towards ameliorating the progression of muscular dystrophies. PGC-1α is influenced by different patho-physiological/pharmacological stimuli. Natural products have been reported to display modulatory effects on PPARγ activation with fewer side effects in comparison to synthetic drugs. Taken together, this review summarizes the current knowledge on Duchenne muscular dystrophy, focusing on the potential effects of natural compounds, acting as regulators of PGC-1α.

Background: Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease, the prevalence of which has increased over the years. The management of this pathology is not clear, and a specific pharmacological drug that can treat NAFLD is not available. In this sense, efforts are focused on the potential use of compounds with a natural origin that can contribute to reversing hepatic steatosis. Supplementation with probiotics, live microorganisms, is a potential strategy for the management of NAFLD. Methods: In the present review, the available information on the potential therapeutic effects of probiotics in NAFLD, mainly in animal models and in some clinical trials, is summarized. Results: Studies carried out using animal models of NAFLD induced by a high-fat diet have shown the beneficial effects of probiotic supplementation in reducing liver steatosis and normalizing the blood lipid profile and liver enzyme activities. In addition, a decrease in lipogenesis and an increase in lipolysis have been observed, together with a reduction in the pro-oxidative and pro-inflammatory state and a normalization of intestinal dysbiosis. Clinical trials have reported a decrease in the serum transaminases and an improved lipid profile, as well as a reduction in inflammatory markers. Conclusions: In conclusion, probiotic supplementation can be used as a potential therapy for the management of NAFLD.

Plastic pollution in the oceans is a growing problem, with negative effects on exposed species and ecosystems. Xyrichtys novacula L. is a very important fish species both culturally and economically in the Balearic Islands. The aim of the present study was to detect and categorise the presence of microplastics (MPs) in the digestive tract of X. novacula, as well as the existence of oxidative stress in the liver. For this purpose, the fish were categorised into two groups based on the number of MPs observed in the digestive tracts: a group with no or low presence of MPs (0–3 items) and a group with a higher presence of MPs (4–28 items). MPs were found in 89% of the specimens analysed, with a dominance of fibre type and blue colour. Regarding the type of polymer, polycarbonate was the most abundant, followed by polypropylene and polyethylene. For the group with a greater presence of MPs, the activities of the antioxidant enzymes glutathione peroxidase and glutathione reductase, as well as the phase II detoxification enzyme glutathione s-transferase, were higher than the activities observed in fish with little to no presence of MPs. The activities of catalase and superoxide dismutase and the levels of malondialdehyde did not show significant differences between both groups. In conclusion, these results demonstrate the presence of MPs in the digestive tract of X. novacula and the existence of an antioxidant and detoxification response, mainly based on the glutathione-based enzymes.

Hepatic fat accumulation is the hallmark of non-alcoholic fatty liver disease (NAFLD). Our aim was to determine the plasma levels of oxylipins, free polyunsaturated fatty acids (PUFA) and markers of lipid peroxidation in patients with NAFLD in progressive stages of the pathology. Ninety 40–60-year-old adults diagnosed with metabolic syndrome were distributed in without, mild, moderate or severe NAFLD stages. The free PUFA and oxylipin plasma levels were determined by the UHPLC–MS/MS system. The plasma levels of oxylipins produced by cyclooxygenases, lipoxygenases and cytochrome P450, such as prostaglandin 2α (PGF2α), lipoxinB4 and maresin-1, were higher in severe NAFLD patients, pointing to the coexistence of both inflammation and resolution processes. The plasma levels of the saturated oxylipins 16-hydroxyl-palmitate and 3-hydroxyl-myristate were also higher in the severe NAFLD patients, suggesting a dysregulation of oxidation of fatty acids. The plasma 12-hydroxyl-estearate (12HEST) levels in severe NAFLD were higher than in the other stages, indicating that the hydroxylation of saturated fatty acid produced by reactive oxygen species is more present in this severe stage of NAFLD. The plasma levels of 12HEST and PGF2α are potential candidate biomarkers for diagnosing NAFLD vs. non-NAFLD. In conclusion, the NAFLD progression can be monitored by measuring the plasma levels of free PUFA and oxylipins characterizing the different NAFLD stages or the absence of this disease in metabolic syndrome patients.

Non-alcoholic fatty liver disease (NAFLD) shows liver fat depots without alcohol consumption. NAFLD does not have specific drug therapies, with a healthy lifestyle and weight loss being the main approaches to prevent and treat NAFLD. The aim was to assess the antioxidant and pro-inflammatory state in patients with NAFLD after 12-month-lifestyle intervention depending on the change in adherence to a Mediterranean diet (AMD). Antioxidant and inflammatory biomarkers were measured in 67 adults (aged 40–60 years old) diagnosed with NAFLD. Anthropometric parameters and dietary intake were measured by a validated semi-quantitative 143-item food frequency questionnaire. The nutritional intervention improved anthropometric and biochemical parameters after a 12-month follow-up. However, decreases in alanine aminotransferase (ALT) and C reactive protein (CRP) were higher in participants with high AMD, which also showed higher improvement in physical fitness (Chester step test) and intrahepatic fat contents. The intervention reduced plasma levels of malondialdehyde, myeloperoxidase, zonulin, and omentin, and increased resolvin D1 (RvD1), whereas the decrease in leptin, ectodysplasin-A (EDA), cytokeratin-18 (CK-18), interleukin-1ra (IL-1ra) and endotoxin was only significant in participants with higher AMD. The current study showed that a one-year nutritional intervention improved main NAFLD features such as body mass index, IFC, liver enzymes, and prooxidant and proinflammatory status. There was also a decrease in the concentration of plasmatic endotoxin, suggesting an improvement in intestinal permeability. These health benefits were more evident in participants that improved AMD to a greater extent. The trial was registered at ClinicalTrials.gov with registry number NCT04442620.

The global distribution and presence of plastic, at all levels of the water column, has made plastic debris one of today’s greatest environmental challenges. The ingestion and entanglement of plastic-containing marine debris has been documented in more than 60% of all cetacean species. In light of the increasing pressure on cetaceans, and the diversity of factors that they face, the aim of this work is to provide evidence of the impact of plastic debris on stranded cetaceans, in terms of ingestion and entanglement, in the Balearic Islands for the first-time. Detailed examinations, necropsies, and plastic debris analysis were performed on 30 of the 108 cetaceans stranded between 2019 and 2022. Specimens belonging to five different species, Stenella coeruleoalba, Tursiops truncatus, Grampus griseus, Balaenoptera physalus, and Physeter macrocephalus, were evaluated. Ten percent of the cetaceans (N = 3) presented plastic debris in their stomach, with one case of obstruction and perforation. Fishery gear fragments (ropes and nets) were found in two adults of T. truncatus, whereas packaging debris (plastic bag, packing straps, and plastic sheets) were found in a juvenile P. macrocephalus. Plastic items analysed by Fourier transform infrared spectroscopy (FT-IR) reported three polymer types: polypropylene, polyamide, and high-density polypropylene. A total of seven cases of entanglement were recorded during the study, affecting four different species (S. coeruleoalba, T. truncatus, P. macrocephalus, and Megaptera novaeangliae). Only two individuals were freed from the nets, although one died after a week, whereas the rest were already found dead. In conclusion, data collected in the present study provided evidence of plastic ingestion and entanglement in cetaceans of the Balearic Islands for the first-time, thus highlighting the need for the regular examination of stranded cetaceans (as they are top predators) in future research to better understand the effects of these pollutants.

Background: A Mediterranean diet (MedDiet) is recommended as a therapy for non-alcoholic fatty liver disease (NAFLD) because there is no specific pharmacological treatment for this disease. Objective: To assess the relationship between the adherence to the Mediterranean diet and the intrahepatic fat content (IFC), levels of oxidative stress, and inflammation biomarkers after a 6-month lifestyle intervention in NAFLD patients. Methods: Patients diagnosed with NAFLD (n = 60 adults; 40–60 years old) living in the Balearic Islands, Spain, were classified into two groups, according to the adherence to the MedDiet after 6 months of lifestyle intervention. Anthropometry, blood pressure, IFC, maximal oxygen uptake, and pro/antioxidant and inflammatory biomarkers were measured in plasma and in PBMCs before and after the intervention. Results: Reductions in weight, body mass index, IFC, blood pressure levels, circulating glucose, glycosylated hemoglobin, and markers of liver damage—aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), and cytokeratin 18 (CK-18)—were observed after the intervention. The highest reductions were observed in the group with the best adherence to the MedDiet. A significant improvement in cardiorespiratory fitness was also observed in the group with a higher adherence. The activities of catalase in plasma and catalase and superoxide dismutase in blood mononuclear cells increased only in the group with a higher adherence, as well as the catalase gene expression in the blood mononuclear cells. The plasma levels of malondialdehyde and myeloperoxidase decreased, and resolvin-D1 increased in both groups after the intervention, whereas interleukin-6 levels decreased only in the group with a higher adherence to the MedDiet. Conclusions: A greater adherence to the MedDiet is related to greater improvements in IFC, cardiorespiratory fitness, and pro-oxidative and proinflammatory status in NAFLD patients after a 6-month nutritional intervention based on the MedDiet.

Obesity and overweight are disorders with high impact on the morbidity and mortality of chronic diseases, such as type 2 diabetes mellitus (T2DM) and cardiovascular diseases (CVD). We aim to assess the effects of 2-year nutritional and lifestyle intervention on oxidative and inflammatory status in individuals of 55 years of age and over at high CVD risk. Participants (n = 100 individuals of 55 years of age and over living in the Balearic Islands, Spain) were randomized into control and intervention group. Anthropometric and haematological parameters, blood pressure and physical activity were measured before and after the intervention. Oxidative and inflammatory biomarkers in plasma, urine, peripheral blood mononuclear cells (PBMCs) and neutrophils were determined. A higher reduction in abdominal obesity, blood pressure and triglycerides levels was observed after a 2-year intervention. An improvement of oxidative stress and proinflammatory status was demonstrated with a significant reduction in myeloperoxidase, xanthine oxidase, malondialdehyde and monocyte chemoattractant protein-1 (MCP1) levels, and an increase in polyphenols in plasma was observed. A decrease in reactive oxygen species production in PBMCs and neutrophils levels after zymosan and lipopolysaccharide activation was found in the intervention group with respect to the control group. The intervention with hypocaloric Mediterranean Diet and customized physical activity improves oxidative stress and proinflammatory status and could contribute to decreasing the CVD risk.

Non-alcoholic fatty liver disease (NAFLD) is a disorder characterized by the excessive accumulation of lipids in the liver parenchyma. To date, there is no effective pharmacological treatment against NAFLD. Objective: To assess the relationship between the improvement of the intrahepatic fat content (IFC) in patients with NAFLD and metabolic syndrome and biomarkers of oxidative stress and inflammation after 6 months of lifestyle intervention. Patients diagnosed with NAFLD (n = 60 adults; 40–60 years old) residing in the Balearic Islands, Spain, were distributed in tertiles attending the improvement of IFC calculated by magnetic resonance imaging (MRI). Anthropometrics, blood pressure, maximal oxygen uptake, and pro/antioxidant and inflammatory biomarkers were determined in plasma before and after the lifestyle intervention. The improvement in IFC levels was higher in tertile 3 with respect to tertiles 2 and 1. The greatest improvement in IFC is related to cardiorespiratory fitness and adherence to the Mediterranean diet (ADM). Higher reductions in weight, body mass index (BMI), and alanine aminotransferase (ALT) were observed in tertile 3 with respect to tertile 1 after 6 months of intervention. The improvement in catalase, irisin, and cytokeratin 18 plasma levels were higher in tertile 3, whereas no differences were observed in superoxide dismutase activity. Malondialdehyde and protein carbonyl levels, as biomarkers of oxidative damage, remained unchanged in all groups. The present data show that the reduction of IFC is associated with an improvement in pro/antioxidant and pro-inflammatory status and a better cardiorespiratory fitness in NAFLD patients.

Metabolic syndrome (MetS) is characterized by increased pro-oxidative stress and a pro-inflammatory state. Several studies emphasized the protective effect of the Mediterranean dietary pattern (MDP). To assess the oxidative and inflammatory state according to the adherence to MDP using biomarkers in patients with MetS. Antioxidant and pro-inflammatory biomarkers were determined in plasma, peripheral blood mononuclear cells (PBMCs), and neutrophils of adults (aged 55–75 years old; 60% women) with MetS living in Mallorca (Spain). Anthropometrics, dietary intake by a validated semi-quantitative 143-item food frequency questionnaire, and a Dietary Inflammatory Index were measured. Patients with low adherence to MDP showed higher levels of glycated haemoglobin A1c and triglycerides, and lower levels of HDL cholesterol. Plasma levels of interleukin-1β, IL-6, IL-15, tumour necrosis factor α, xanthine oxidase, and ghrelin, and activities of superoxide dismutase, and myeloperoxidase were higher in subjects with low adherence to the MDP. Reactive oxygen species production in PBMCs and neutrophils stimulated with lipopolysaccharide was higher in participants with low adherence to the MDP. Patients with MetS and higher adherence to the MDP showed less altered anthropometric parameters, blood biochemical profile, and better oxidative and inflammatory status.

Diazotrophs or N2-fixers are one of the most ecologically significant groups in marine ecosystems (pelagic and benthic). Inorganic phosphorus (PO43–) and iron (Fe) can limit the growth and N2-fixing capacities of cyanobacteria. However, studies investigating co-limitation of these factors are lacking. Here, we added different concentrations of PO43– and Fe in two cyanobacterial species whose relatives can be found in seagrass habitats: the unicellular Halothece sp. (PCC 7418) and the filamentous Fischerella muscicola (PCC 73103), grown under different nitrate (NO3–) concentrations and under N2 as sole N source, respectively. Their growth, pigment content, N2-fixation rates, oxidative stress responses, and morphological and cellular changes were investigated. Our results show a serial limitation of NO3– and PO43– (with NO3– as the primary limiting nutrient) for Halothece sp. Simultaneous co-limitation of PO43– and Fe was found for both species tested, and high levels of Fe (especially when added with high PO43– levels) inhibited the growth of Halothece sp. Nutrient limitation (PO43–, Fe, and/or NO3–) enhanced oxidative stress responses, morphological changes, and apoptosis. Furthermore, an extensive bio-informatic analysis describing the predicted Pho, Fur, and NtcA regulons (involved in the survival of cells to P, Fe, and N limitation) was made using the complete genome of Halothece sp. as a model, showing the potential of this strain to adapt to different nutrient regimes (P, Fe, or N).

Background: Pork lard (PL) is traditionally used as an anti-inflammatory agent. We propose to demonstrate the anti-inflammatory properties of PL, and elucidate which compounds could be responsible for the anti-inflammatory effects. Methods: The anti-inflammatory effects of PL were tested in a rat model of zymosan-induced hind paw inflammation. Further, the hydroalcoholic extract from PL was obtained, the composition analyzed, and the anti-inflammatory activity of the extracts and isolated components assayed using immune cells stimulated with lipopolysaccharide (LPS). Results: Applying the ointment on the inflamed rat feet reduced the foot diameter, foot weight, and activities of antioxidant enzymes and inflammatory markers of circulating neutrophils. The main components of the hydroalcoholic extract were 5-dodecanolide, oleamide, hexadecanoic acid, 9-octadecenoic acid, hexadecanamide, and resolvin D1. Conclusions: PL reduces the immune response in an animal model stimulated with zymosan. Hydroalcoholic PL extract and its components (5-Dodecanolide, Oleamide, and Resolvin D1) exerted an anti-inflammatory effect on LPS-stimulated neutrophils and peripheral mononuclear cells reducing the capability to produce TNFα, as well as the activities of antioxidant and pro-inflammatory enzymes. These effects are attributable to 5-dodecanolide, although the effects of this compound alone do not reach the magnitude of the anti-inflammatory effects observed by the complete hydroalcoholic extract.

Oxidative stress (OxS) has been linked to several chronic diseases and is recognized to have both major causes and consequences. The use of antioxidant-based nutraceuticals has been licensed as an optimal tool for management of OxS-related diseases. Currently, great interest is focused on the valorization of agri-food by-products as a source of bioactive compounds, including polyphenols. In this sense, we evaluated the efficacy of a novel nutraceutical formulation based on polyphenolic extract from Aglianico cultivar grape pomace (registered as Taurisolo®). In particular, we tested both native and in vitro gastrointestinal digested forms. The two extracts have been used to treat ex vivo neutrophils from subjects with metabolic syndrome, reporting a marked antioxidant activity of Taurisolo®, as shown by its ability to significantly reduce both the levels of reactive oxygen species (ROS) and the activities of catalase and myeloperoxidase in the cell medium after stimulation of neutrophils with phorbol 12-myristate 13-acetate (PMA). Interestingly, we observed an increase in intracellular enzymatic activities in PMA-treated cells, suggesting that Taurisolo® polyphenols might be able to activate nuclear factors, up-regulating the expression of this target antioxidant gene. In addition, Taurisolo® reversed the increase in malondialdehyde induced by PMA; reduced the expression of pro-inflammatory genes such as cyclooxygenase 2 (COX-2), tumor necrosis factor alpha (TNFα) and myeloperoxidase (MPO); and induced the expression of the anti-inflammatory cytokine IL-10. Overall, these results suggest the efficacy of Taurisolo® in contrasting the OxS at blood level, providing evidence for its therapeutic potential in the management of OxS-related pathological conditions in humans.

Background: Obesity is an important pathology in public health worldwide. Obese patients are characterized by higher cardiovascular risk and a pro-inflammatory profile. Objective: To assess the oxidative stress in peripheral blood mononuclear cells (PBMCs) and inflammatory biomarkers in plasma in adults with normal weight, overweight and obesity. Methods: One hundred and fifty adults (55-80-years-old; 60% women) from the Balearic Islands, Spain, were recruited and classified according to body mass index (BMI). Anthropometric measurements were carried out, fasting blood samples were collected and plasma and PBMCs were obtained. Biochemical parameters, hemogram, antioxidant enzyme activities and protein levels, reactive oxygen species production (ROS), malondialdehyde (MDA), and cytokine (tumour necrosis factor, TNFα, and interleukin 6, IL-6) levels were measured. Results: Glycaemia, triglyceridemia, abdominal obesity, and waist-to-height ratio (WHtR) were higher, and HDL-cholesterol was lower in obese patients. MDA and TNFα plasma levels were higher in the obese compared to normal-weight group, while the levels of IL-6 were higher in both obese and overweight subjects with respect to normal-weight peers. The activities of all antioxidant enzymes in PBMCs as well as the production ROS progressively increased with BMI. The protein levels of catalase in PBMCs were higher in obese and glutathione reductase in obese and overweight subjects compared to normal-weight peers. No other differences were observed. Conclusion: The current results show that overweight and obesity are related to an increase in pro-oxidant and proinflammatory status in plasma and PBMCs. The studied biomarkers may be useful for monitoring the progression/reversal of obesity.

The endemic fan mussel (Pinna nobilis) in the Mediterranean Sea is at high risk of disappearance due to massive mortality events. The aim of the study was to evaluate the antioxidant response of P. nobilis collected in the Balearic Islands (Western Mediterranean) before and after the mass mortality event. Individuals collected before (between 2011 and 2012) and after (between 2016 and 2017) the event were analyzed by histological, molecular, and biochemical methods to compare pathogenic loads and biochemical responses. All the individuals collected during 2016–2017 presented symptoms of the disease and were positive for Haplosporidium pinnae, while acid-fast bacteria or/and Gram-negative bacteria were detected in some individuals of both sampling periods. The activities of the antioxidant enzymes catalase and superoxide dismutase in the gills were significantly lower in P. nobilis affected with the parasite compared to those in the asymptomatic ones, while levels of malondialdehyde, as an indicator of lipid peroxidation, were higher in infected individuals. When analyzing the differential effects of H. pinnae and Mycobacterium sp. on P. nobilis, it was observed that significant effects on biomarkers were only observed in the presence of H. pinnae. Co-infection of P. nobilis by H. pinnae with other pathogens such as Mycobacterium sp. constitutes a serious problem due to its high mortality rate in the Balearic Island waters. This concerning situation for P. nobilis is favored by a reduction in antioxidant defenses related to H. pinnae infection that induces oxidative stress and cell damage.

Background: Nonalcoholic fatty liver disease (NAFLD) is characterized by excessive fat accumulation, especially triglycerides, in hepatocytes. If the pathology is not properly treated, it can progress to nonalcoholic steatohepatitis (NASH) and continue to fibrosis, cirrhosis or hepatocarcinoma. Objective: The aim of the current research was to identify the plasma biomarkers of liver damage, oxidative stress and inflammation that facilitate the early diagnosis of the disease and control its progression. Methods: Antioxidant and inflammatory biomarkers were measured in the plasma of patients diagnosed with NAFLD (n = 100 adults; 40–60 years old) living in the Balearic Islands, Spain. Patients were classified according to the intrahepatic fat content (IFC) measured by magnetic resonance imaging (MRI). Results: Circulating glucose, glycosylated haemoglobin, triglycerides, low-density lipoprotein-cholesterol, aspartate aminotransferase and alanine aminotransferase were higher in patients with an IFC ≥ 2 of NAFLD in comparison to patients with an IFC of 0 and 1. The plasma levels of catalase, irisin, interleukin-6, malondialdehyde, and cytokeratin 18 were higher in stage ≥2 subjects, whereas the resolvin D1 levels were lower. No differences were observed in xanthine oxidase, myeloperoxidase, protein carbonyl and fibroblast growth factor 21 depending on liver status. Conclusion: The current available data show that the severity of NAFLD is associated with an increase in oxidative stress and proinflammatory status. It may be also useful as diagnostic purpose in clinical practice.

The beneficial effects of exercise for the treatment and prevention of metabolic syndrome pathologies have been related to its anti-inflammatory and antioxidant effects. Dietary nitrate supplementation is an emerging treatment strategy to alleviate the symptoms of metabolic syndrome affections and to improve vascular function. In this double-blind crossover trial, metabolic syndrome patients performed two exercise tests for 30 min at 60–70% maximal heart rate after the intake of a placebo or a nitrate-enriched beverage. Acute exercise increased the plasma concentration of TNFα, intercellular adhesion molecule ICAM1, PGE1, PGE2 and the newly detected 16-hydroxypalmitic acid (16-HPAL) in metabolic syndrome patients. The cytokine and oxylipin production by peripheral blood mononuclear cells (PBMCs) and neutrophils could be responsible for the plasma concentrations of TNFα and IL6, but not for the plasma concentration of oxylipins nor its post-exercise increase. The intake of sodium nitrate 30 min before exercise increased the concentration of nitrate and nitrite in the oral cavity and plasma and reduced the oxygen cost of exercise. Additionally, nitrate intake prevented the enhancing effects of acute exercise on the plasma concentration of TNFα, ICAM1, PGE1, PGE2 and 16-HPAL, while reducing the capabilities of PBMCs and neutrophils to produce oxylipins.

Metabolic syndrome (MetS) is associated with increased risk of developing diabetes and cardiovascular diseases. MetS is also characterized by an increase of oxidative stress which contributes to impaired inflammation, vascular function, and atherosclerosis. The aim was to assess the oxidative stress and inflammatory markers in plasma and PBMCs in adults with or without MetS. Antioxidant and inflammatory parameters were measured in peripheral blood mononuclear cells (PBMCs) of 80 men and 80 women over 55 to 80-years-old residing in the Balearic Islands without previously documented cardiovascular disease. Circulating leukocytes, neutrophils, lymphocytes, basophils, and monocytes were higher in MetS subjects with respect to those without MetS. Plasma levels of malondialdehyde, tumor necrosis factor α (TNFα), and interleukin 6 (IL-6) levels were higher in MetS subjects in both genders, but the superoxide dismutase activity was lower. The myeloperoxidase plasma activity was higher in the MetS male subjects. Higher activities and protein levels of catalase and glutathione reductase in PBMCs were observed in MetS subjects in both genders. Obtained data show that MetS is associated with oxidative stress and a proinflammatory state and with high antioxidant defenses in PBMCs probably derived from a pre-activation state of immune cells.

Plants and their corresponding botanical preparations have been used for centuries due to their remarkable potential in both the treatment and prevention of oxidative stress-related disorders. Aging and aging-related diseases, like cardiovascular disease, cancer, diabetes, and neurodegenerative disorders, which have increased exponentially, are intrinsically related with redox imbalance and oxidative stress. Hundreds of biologically active constituents are present in each whole plant matrix, providing promissory bioactive effects for human beings. Indeed, the worldwide population has devoted increased attention and preference for the use of medicinal plants for healthy aging and longevity promotion. In fact, plant-derived bioactives present a broad spectrum of biological effects, and their antioxidant, anti-inflammatory, and, more recently, anti-aging effects, are considered to be a hot topic among the medical and scientific communities. Nonetheless, despite the numerous biological effects, it should not be forgotten that some bioactive molecules are prone to oxidation and can even exert pro-oxidant effects. In this sense, the objective of the present review is to provide a detailed overview of plant-derived bioactives in age-related disorders. Specifically, the role of phytochemicals as antioxidants and pro-oxidant agents is carefully addressed, as is their therapeutic relevance in longevity, aging-related disorders, and healthy-aging promotion. Finally, an eye-opening look into the overall evidence of plant compounds related to longevity is presented.

Background Caloric restriction induces mitochondrial biogenesis and improves physical fitness in rodents. We aimed to provide evidence of how caloric restriction affects the body composition and physical performance of trained athletes and to evaluate the possible impact of an every-other-day feeding diet on nutritional deficiencies of micronutrients and essential fatty acids. Methods The study was performed with 12 healthy male athletes by carrying out a 33% caloric restriction with respect to their usual diet. Athletes performed a maximal exercise stress test both before and after the caloric restriction period. Blood samples were taken before and after the caloric restriction at basal conditions and 30 min post-exercise. Although energy intake was reduced by about 33%, the contribution of carbohydrates, proteins, and lipids to total energy intake during the caloric restriction was similar to the original diet. Results The caloric restriction reduced the daily specific micronutrient intake to values lower than 90% of recommended dietary allowances. No effects were observed in blood parameters related to iron metabolism and tissue damage, glucose levels, lipid profiles, or erythrocyte fatty acid composition. In addition, oxidative damage markers decreased after the nutritional intervention. The caloric restriction intervention significantly reduced body weight and trunk, arm, and leg weights; it also caused a decrease in fat and lean body mass, the energy expenditure rate when performing a maximal exercise stress test, and the energy cost to run one meter at various exercise intensities. Furthermore, the intervention ameliorated the onset of the anaerobic phase of exercise. Conclusion A caloric restriction improves athletes’ performance and energy efficiency, but reduces the daily intake of micronutrients; so, when caloric restriction programs are implemented micronutrient supplementation should be considered. Trial registration The project was registered at ClinicalTrials.gov (NCT02533479).

Panax ginseng is a well-known economic medical plant that is widely used in Chinese traditional medicine. This species contains a unique class of natural products—ginsenosides. Recent clinical and experimental studies have presented numerous lines of evidence on the promising role of ginsenosides on different diseases including neurodegenerative diseases, cardiovascular diseases, and certain types of cancer. Nowadays, most of the attention has focused on ginsenoside Rd as a neuroprotective agent to attenuate ischemic stroke damages. Some of the evidence showed that ginsenoside Rd ameliorates ischemic stroke-induced damages through the suppression of oxidative stress and inflammation. Ginsenoside Rd can prolong neural cells' survival through the upregulation of the endogenous antioxidant system, phosphoinositide-3-kinase/AKT and extracellular signal-regulated protein kinase 1/2 pathways, preservation of mitochondrial membrane potential, suppression of the nuclear factor-kappa B, transient receptor potential melastatin, acid sensing ion channels 1a, poly(ADP-ribose) polymerase-1, protein tyrosine kinase activation, as well as reduction of cytochrome c-releasing and apoptosis-inducing factor. In the current work, we review the available reports on the promising role of ginsenoside Rd on ischemic stroke. We also discuss its chemistry, source, and the molecular mechanism underlying this effect.

Markers of oxidative stress in the hepatopancreas and carotenoid and vitamin E content in the carapace of the invasive crab Percnon gibbesi and the native crab Pachygrapsus marmoratus were compared as indicators of their physiological condition and environmental adaptation. Crabs similar in size were collected from coastal waters of Portals Vells (Mallorca Island, Spain; 39°28’18.79”N, 2°28’19.63”E) at < 1 m depth. Vitamin E levels were significantly higher in P. marmoratus than in P. gibbesi, whereas all carotenoid concentrations, except astaxanthin, were significantly higher in P. gibbesi. Catalase, glutathione peroxidase and glutathione reductase activities were significantly greater in P. marmoratus. Malondialdehyde concentration, a marker of lipid peroxidation, was higher in the hepatopancreas of P. gibbesi. The differences in carotenoid and vitamin E contents and in the antioxidant enzyme activities are a reflection of the different physiological activity of the two species and may suggest that P. gibbesi is not a potential competitor for the native crab P. marmoratus.

Background: There is much evidence indicating that natural substances from edible and medicinal plants possess powerful antioxidant and hepatoprotective activities. The objective of the present study was to investigate the potential hepatoprotective effect of silymarin in fish exposed to malathion. Methods: Zebra cichlid fish were allocated into five groups of which one group received normal feed and served as control. Fish from group 2 were treated with 0.1 mg.L-1 malathion. Fish from group 3 and 4 were fed with enriched diet with 1400 mg and 2100 mg silymarin per 1 kg feed, respectively. While fish from group 5 and 6 were fed with enriched diet with 1400 mg and 2100 mg silymarin per 1 kg feed, respectively and simultaneously were treated with 0.1 mg.L-1 malathion for 15 days. Activities of hepatic enzymes including alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and lactate dehydrogenase were evaluated. Oxidative stress was ascertained by measuring malondialdehyde as marker of lipid peroxidation and total cellular antioxidant capacity. Results: Exposure to malathion caused a significant increase in MDA levels and altered AST, ALT, ALP and LDH activities in liver tissues (p

Fenpropathrin is a new pyrethroid insecticide used to control crop pests. The aim of this study was to evidence fenpropathrin-induced oxidative stress and alterations in biochemical parameters in the freshwater fish, Alburnus mossulensis. Total antioxidant capacity, malondialdehyde (MDA), catalase activity (CAT), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), creatine phosphokinase (CK), acetylcholinesterase (AChE) in the whole body extract were measured in A. mossulensis after exposure to sub-lethal concentrations of fenpropatrin (approximately equal to 1, 2, 3, 5 and 10% of 96 h LC50) for 15 days. The 24, 48, 72 and 96 h LC50 of the fenpropathrin for A. mossulensis was 562.28±45.19, 218.18±18.75, 136.18±11.90 and 121.38±11.84 µg/L at 24±2 °C. Exposure to 2.75, 5.50 and 12.6 µg/L fenpropathrin significantly increased AST activity in fish. A significant increase in the ALP and LDH activities was observed in fish after a 15 day exposure to 1.25, 5.50 and 12.60 µg/L fenpropathrin. Fenpropatrin significantly induced lipid peroxidation and increased MDA levels in fish. Compared with the control group, total protein levels in fish decreased after exposure to 2.75, 5.50 and 12.60 µg/L fenpropathrin on day 15. Total antioxidant capacity, AChE and CPK activities in fish exposed to fenproparthin were significantly lower than control group. There was a significant increase in the CAT and ALT activities in fish after exposure to 5.50 and 12.60 µg/L fenpropathrin. In conclusion, fenpropathrin has the potential to disrupt biochemical parameters in A. mossulensis and to induce oxidative stress.

Diabetes mellitus is one of the major health problems in the world, the incidence and associated mortality are increasing. Inadequate regulation of the blood sugar imposes serious consequences for health. Conventional antidiabetic drugs are effective, however, also with unavoidable side effects. On the other hand, medicinal plants may act as an alternative source of antidiabetic agents. Examples of medicinal plants with antidiabetic potential are described, with focuses on preclinical and clinical studies. The beneficial potential of each plant matrix is given by the combined and concerted action of their profile of biologically active compounds.

Metabolic syndrome is characterized by an increase in oxidative stress and chroniclow-grade inflammation. The effects of an exercise test at 60–70% of the maximum capacity wasevaluated on inflammatory and antioxidant response in elderly people suffering from metabolicsyndrome. Exercise induced significant increases in plasma levels of inflammatory cytokines andmalondialdehyde. The expression of these cytokines and antioxidant enzymes were also increasedin peripheral blood mononuclear cells. In addition, plasma levels of tumour necrosis factor alphawere unchanged. In conclusion, the exercise test induces a situation of oxidative stress thatpromotes the activation of a proinflammatory cytokine cascade.

The aim was to assess the trace element contents in toenails of older adults and its association with regular physical activity. Cross-sectional multicentre study in Spain, collecting data from a random sample of 380 participants (54% female) aged 55-80 years (men) and 60-80 years (women) with no previously documented cardiovascular disease. Physical activity performed was measured using the Minnesota Leisure-time Physical Activity Questionnaire. The 25 most inactive and 25 most active individuals for each sex were selected for this study (final sample n = 100). Anthropometric measurements were performed and toenail samples collected for calcium (Ca), chromium (Cr), iron (Fe), cobalt (Co), nickel (Ni), zinc (Zn), selenium (Se) and mercury (Hg) analysis. Significant differences between sexes were reported in Ca concentrations, women having lower concentrations than men. No differences were reported in trace element contents between active and inactive men. Active women showed higher Ca, Cr, Fe, Co, and Zn and lower Hg contents than their inactive peers (all p

The term “antioxidant„ is one of the most confusing definitions in biological/medical sciences. In chemistry, “antioxidant„ is simply conceived “a compound that removes reactive species, mainly those oxygen-derived„, while in a cell context, the conceptual definition of an antioxidant is poorly understood. Indeed, non-clinically recommended antioxidants are often consumed in large amounts by the global population, based on the belief that cancer, inflammation and degenerative diseases are triggered by high oxygen levels (or reactive oxygen species) and that through blocking reactive species production, organic unbalances/disorders can be prevented and/or even treated. The popularity of these chemicals arises in part from the widespread public mistrust of allopathic medicine. In fact, reactive oxygen species play a dual role in dealing with different disorders, since they may contribute to disease onset and/or progression but may also play a key role in disease prevention. Further, the ability of the most commonly used supplements, such as vitamins C, E, selenium, and herbal supplements to decrease pathologic reactive oxygen species is not clearly established. Hence, the present review aims to provide a nuanced understanding of where current knowledge is and where it should go.

Genus Mentha, a member of Lamiaceae family, encompasses a series of species used on an industrial scale and with a well-described and developed culture process. Extracts of this genus are traditionally used as foods and are highly valued due to the presence of significant amounts of antioxidant phenolic compounds. Many essential oil chemotypes show distinct aromatic flavor conferred by different terpene proportions. Mint extracts and their derived essential oils exert notable effects against a broad spectrum of bacteria, fungi or yeasts, tested both in vitro or in various food matrices. Their chemical compositions are well-known, which suggest and even prompt their safe use. In this review, genus Mentha plant cultivation, phytochemical analysis and even antimicrobial activity are carefully described. Also, in consideration of its natural origin, antioxidant and antimicrobial properties, a special emphasis was given to mint-derived products as an interesting alternative to artificial preservatives towards establishing a wide range of applications for shelf-life extension of food ingredients and even foodstuffs. Mentha cultivation techniques markedly influence its phytochemical composition. Both extracts and essential oils display a broad spectrum of activity, closely related to its phytochemical composition. Therefore, industrial implementation of genus Mentha depends on its efficacy, safety and neutral taste.

BACKGROUND AND AIMS:The increase in overweight and obese children may be linked to increased rates of liver damage and dyslipidaemia. This study aimed to explore the associations of liver biomarkers with overweight/obesity and dyslipidaemia in Mexican children. METHODS:The study was a population-based cross-sectional nutritional survey carried out in the State of Nuevo León, Mexico. The study included a 414 subjects aged between 2 and 10 years old (47.8% girls) who took part in the State Survey of Nutrition and Health-Nuevo León 2011/2012. Associations between alanine aminotransferase (ALT) and aspartate aminotransferase (AST), ALT/AST ratio, and major components of serum lipid profile were assessed. RESULTS:Children with high ALT (defined as ≥P75) showed higher prevalence of dyslipidaemia than their counterparts, with high prevalence of high TChol (P = 0.053), non-HDL-chol, TG, and low HDL-chol. Children with an AST/ALT ≥T3 ratio were 0.43-times (95% CI: 0.25-0.74) and 0.27-times (95% CI: 0.17-0.44) low likely to be overweight/obese and to have dyslipidaemia than those with an AST/ALT

We analyzed the effects of the clinical hyperbaric oxygen therapy (HBOT) on the plasma antioxidant response and levels of endothelin-1, Interleukine-6 (IL-6) and vascular endothelial growth factor (VEGF) in patients with chronic wounds (20.2±10.0 months without healing). They received 20 HBOT sessions (five sessions/week), and blood samples were obtained at sessions 1, 5 and 20 before and 2 hours after the HBOT. An additional blood sample was collected 1 month after wound recovery. Serum creatine kinase activity decreased progressively in accordance with the wound healing. Plasma catalase activity significantly increased after the first and fifth sessions of HBOT. Plasma myeloperoxidase activity reported significantly lower values after sessions. Plasma VEGF and IL-6 increased after sessions. Endothelin-1 levels were progressively decreasing during the HBOT, being significant at the session 20. Plasma malondialdehyde concentration was significantly reduced at the last session. Both creatine kinase activity and malondialdehyde levels were maintained lower 1 month after wound recovery respect to initial values. In conclusion, HBOT enhanced the plasma antioxidant defenses and may contribute to activate the healing resolution, angiogenesis and vascular tone regulation by increasing the VEGF and IL-6 release and the endothelin-1 decrease, which may be significant factors in stimulating wound healing.