Antioxidants

Drought stress deleteriously affects growth, development and productivity in plants. So, we examined the silicon effect (2 mmol) and proline (10 mmol) individually or the combination (Si + proline) in alleviating the harmful effect of drought on total phenolic compounds, reactive oxygen species (ROS), chlorophyll concentration and antioxidant enzymes as well as yield parameters of drought-stressed sugar beet plants during 2018/2019 and 2019/2020 seasons. Our findings indicated that the root diameter and length (cm), root and shoot fresh weights (g plant⁻¹) as well as root and sugar yield significantly decreased in sugar beet plants under drought. Relative water content (RWC), nitrogen (N), phosphorus (P) and potassium (K) contents and chlorophyll (Chl) concentration considerably reduced in stressed sugar beet plants that compared with control in both seasons. Nonetheless, lipid peroxidation (MDA), electrolyte leakage (EL), hydrogen peroxide (H₂O₂) and superoxide (O₂^●−) considerably elevated as signals of drought. Drought-stressed sugar beet plants showed an increase in proline accumulation, total phenolic compounds and up-regulation of antioxidant enzymes catalase (CAT) and superoxide dismutase (SOD) activity to mitigate drought effects. Si and proline individually or the combination Si + proline considerably increased root and sugar yield, sucrose%, Chl concentration and RWC, MDA and EL were remarkably reduced. The treatments led to adjust proline and total phenolic compounds as well as CAT and SOD activity in stressed sugar beet plants. We concluded that application of Si + proline under drought stress led to improve the resistance of sugar beet by regulating of proline, antioxidant enzymes, phenolic compounds and improving RWC, Chl concentration and Nitrogen, Phosphorus and Potassium (NPK) contents as well as yield parameters. Full article

Our aim was to assess whether long-term adherence to a Mediterranean diet (MedDiet) and leisure-time physical activity (LTPA) were associated with a lower initiation of cardiovascular drug use. We studied the association between cumulative average of MedDiet adherence and LTPA and the risk of cardiovascular drug initiation in older adults at high cardiovascular risk (PREvención con DIeta MEDiterránea trial participants) non-medicated at baseline: glucose-lowering drugs (n = 4437), antihypertensives (n = 2145), statins (n = 3977), fibrates (n = 6391), antiplatelets (n = 5760), vitamin K antagonists (n = 6877), antianginal drugs (n = 6837), and cardiac glycosides (n = 6954). One-point increases in MedDiet adherence were linearly associated with a decreased initiation of glucose-lowering (HR: 0.76 [0.71–0.80]), antihypertensive (HR: 0.79 [0.75–0.82]), statin (HR: 0.82 [0.78–0.85]), fibrate (HR: 0.78 [0.68–0.89]), antiplatelet (HR: 0.79 [0.75–0.83]), vitamin K antagonist (HR: 0.83 [0.74; 0.93]), antianginal (HR: 0.84 [0.74–0.96]), and cardiac glycoside therapy (HR: 0.69 [0.56–0.84]). LTPA was non-linearly related to a delayed initiation of glucose-lowering, antihypertensive, statin, fibrate, antiplatelet, antianginal, and cardiac glycoside therapy (minimum risk: 180–360 metabolic equivalents of task-min/day). Both combined were synergistically associated with a decreased onset of glucose-lowering drugs (p-interaction = 0.04), antihypertensive drugs (p-interaction < 0.001), vitamin K antagonists (p-interaction = 0.04), and cardiac glycosides (p-interaction = 0.01). Summarizing, sustained adherence to a MedDiet and LTPA were associated with lower risk of initiating cardiovascular-related medications. Full article

Aims: Angiotensin-converting-enzyme inhibitors (ACE inhibitors) are a cornerstone of drug therapy after myocardial infarction (MI) and improve left ventricular function and survival. We aimed to elucidate the impact of early treatment with the ACE inhibitor ramipril on the hematopoietic response after MI, as well as on the chronic systemic and vascular inflammation. Methods and Results: In a mouse model of MI, induced by permanent ligation of the left anterior descending artery, immediate initiation of treatment with ramipril (10 mg/k/d via drinking water) reduced cardiac inflammation and the number of circulating inflammatory monocytes, whereas left ventricular function was not altered significantly, respectively. This effect was accompanied by enhanced retention of hematopoietic stem cells, Lin⁻Sca1⁻c-Kit⁺CD34⁺CD16/32⁺ granulocyte–macrophage progenitors (GMP) and Lin⁻Sca1⁻c-Kit⁺CD150⁻CD48⁻ multipotent progenitors (MPP) in the bone marrow, with an upregulation of the niche factors Angiopoetin 1 and Kitl at 7 d post MI. Long-term ACE inhibition for 28 d limited vascular inflammation, particularly the infiltration of Ly6C^high monocytes/macrophages, and reduced superoxide formation, resulting in improved endothelial function in mice with ischemic heart failure. Conclusion: ACE inhibition modulates the myeloid inflammatory response after MI due to the retention of myeloid precursor cells in their bone marrow reservoir. This results in a reduction in cardiac and vascular inflammation with improvement in survival after MI. Full article

Dengue fever is a mosquito-borne viral disease of increasing global importance. The disease has caused heavy burdens due to frequent outbreaks in tropical and subtropical areas of the world. The dengue virus (DENV) is generally transmitted between human hosts via the bite of a mosquito vector, primarily Aedes aegypti and Ae. albopictus as a minor species. It is known that the virus needs to alternately infect mosquito and human cells. DENV-induced cell death is relevant to the pathogenesis in humans as infected cells undergo apoptosis. In contrast, mosquito cells mostly survive the infection; this allows infected mosquitoes to remain healthy enough to serve as an efficient vector in nature. Overexpression of antioxidant genes such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione S-transferase (GST), glutaredoxin (Grx), thioredoxin (Trx), and protein disulfide isomerase (PDI) have been detected in DENV2-infected mosquito cells. Additional antioxidants, including GST, eukaryotic translation initiation factor 5A (eIF5a), and p53 isoform 2 (p53-2), and perhaps some others, are also involved in creating an intracellular environment suitable for cell replication and viral infection. Antiapoptotic effects involving inhibitor of apoptosis (IAP) upregulation and subsequent elevation of caspase-9 and caspase-3 activities also play crucial roles in the ability of mosquito cells to survive DENV infection. This article focused on the effects of intracellular responses in mosquito cells to infection primarily by DENVs. It may provide more information to better understand virus/cell interactions that can possibly elucidate the evolutionary pathway that led to the mosquito becoming a vector. Full article

Hepatocellular carcinoma (HCC) is a severe disease that accounts for 80% of liver cancers. Chemotherapy is the primary therapeutic strategy for patients who cannot be treated with surgery or who have late-stage HCC. C₂-ceramide is an effective reagent that has been found to inhibit the growth of many cancer types. The metabolism of C₂-ceramide plays a vital role in the regulation of cell death/cell survival. The phenoxyphenol compound 4-{2,3,5,6-tetrafluoro-4-[2,3,5,6-tetrafluoro-4-(4-hydroxyphenoxy)phenyl]phenoxy}phenol (diTFPP) was found to have a synergistic effect with C₂-ceramide, resulting in considerable cell death in the HA22T HCC cell line. diTFPP/C₂-ceramide cotreatment induced a two- to threefold increase in cell death compared to that with C2-ceramide alone and induced pyknosis. Annexin V/7-aminoactinomycin D (7AAD) double staining and Western blotting indicated that apoptosis was involved in diTFPP/C₂-ceramide cotreatment-mediated cell death. We next analyzed transcriptome alterations in diTFPP/C₂-ceramide-cotreated HA22T cells with next-generation sequencing (NGS). The data indicated that diTFPP treatment disrupted sphingolipid metabolism, inhibited cell cycle-associated gene expression, and induced autophagy and reactive oxygen species (ROS)-responsive changes in gene expression. Additionally, we assessed the activation of autophagy with acridine orange (AO) staining and observed alterations in the expression of the autophagic proteins LC3B-II and Beclin-1, which indicated autophagy activation after diTFPP/C₂-ceramide cotreatment. Elevated levels of ROS were also reported in diTFPP/C₂-ceramide-treated cells, and the expression of the ROS-associated proteins SOD1, SOD2, and catalase was upregulated after diTFPP/C₂-ceramide treatment. This study revealed the potential regulatory mechanism of the novel compound diTFPP in sphingolipid metabolism by showing that it disrupts ceramide metabolism and apoptotic sphingolipid accumulation. Full article

Breast cancer expresses clinically heterogeneous characteristics and requires multipurpose drug development for curing the different tumor subtypes. Many withanolides have been isolated from Physalis species showing anticancer effects, but the anticancer function of physapruin A (PHA) has rarely been investigated. In this study, the anticancer properties of PHA in breast cancer cells were examined by concentration and time-course experiments. In terms of cellular ATP content, PHA inhibited the proliferation of three kinds of breast cancer cells: MCF7 (estrogen receptor (ER)+, progesterone receptor (PR)+/−, human epidermal growth factor receptor 2 (HER2)−), SKBR3 (ER−/PR−/HER2+), and MDA-MB-231 (triple-negative). Moreover, PHA induced G2/M arrest in MCF7 and MDA-MB-231 cells. In terms of flow cytometry, PHA induced the generation of reactive oxygen species (ROS), the generation of mitochondrial superoxide, mitochondrial membrane potential depletion, and γH2AX-detected DNA damage in breast cancer MCF7 and MDA-MB-231 cells, which were suppressed by the ROS inhibitor N-acetylcysteine (NAC). In terms of flow cytometry and Western blotting, PHA induced apoptotic expression (annexin V, and intrinsic and extrinsic apoptotic signaling), which was suppressed by NAC and an apoptosis inhibitor (Z-VAD-FMK), in breast cancer cells. Therefore, PHA is a potential anti-breast-cancer natural product that modulates the oxidative-stress response, cell-cycle disturbance, apoptosis, and γH2AX-detected DNA damage. Full article

This study aimed to determine the impact of sesame meal, selenium (Se), and vitamin E (VitE) on goats’ oxidative status. Thirty mid-lactation crossbred goats were divided into five homogeneous groups, and were fed 1 kg of alfalfa hay and 1.2 kg of concentrates daily. The control group (C) received a basal diet. In the concentrates of the treated groups, 10% of the soybean meal was replaced by sesame meal and no extra VitE or Se (SM), or an extra 60 mg of VitE (SME), or 0.1 mg organic Se (SMSe), or their combination (60 mg VitE and 0,1 mg organic Se/kg of concentrate (SMESe). In the plasma of the goats, the dietary treatments did not affect glutathione reductase, glutathione peroxidase, glutathione transferase, catalase, superoxide dismutase activities, malondialdehyde (MDA) content, or the total antioxidant capacity. A reduction and a trend for lower protein carbonyls content was found in goats fed SM (p = 0.03) and SME (p = 0.06) compared to SMESe. In the milk, the lactoperoxidase activity decreased with SMSe and SMESe. A numerical decrease in the total antioxidant capacity and an increase in the MDA content in the milk of the SMESe group compared with the other treated groups was found. In mid-lactation goats, SM improves the oxidative status of both the organism and the milk. Full article

As a nicotinoid neurotoxic insecticide, imidacloprid (IMI) works by disrupting nerve transmission via nicotinic acetylcholine receptor (nAChR). Although IMI is specifically targeting insects, nontarget animals such as the freshwater shrimp, Neocaridina denticulata, could also be affected, thus causing adverse effects on the aquatic environment. To investigate IMI toxicity on nontarget organisms like N. denticulata, their physiology (locomotor activity, heartbeat, and gill ventilation) and biochemical factors (oxidative stress, energy metabolism) after IMI exposure were examined. IMI exposure at various concentrations (0.03125, 0.0625, 0.125, 0.25, 0.5, and 1 ppm) to shrimp after 24, 48, 72 h led to dramatic reduction of locomotor activity even at low concentrations. Meanwhile, IMI exposure after 92 h caused reduced heartbeat and gill ventilation at high concentrations. Biochemical assays were performed to investigate oxidative stress and energy metabolism. Interestingly, locomotion immobilization and cardiac activity were rescued after acetylcholine administration. Through molecular docking, IMI demonstrated high binding affinity to nAChR. Thus, locomotor activity and heartbeat in shrimp after IMI exposure may be caused by nAChR blockade and not alterations caused by oxidative stress and energy metabolism. To summarize, N. denticulata serves as an excellent and sensitive aquatic invertebrate model to conduct pesticide toxicity assays that encompass physiologic and biochemical examinations. Full article

Idiosyncratic drug-induced liver injury (DILI) is a type of hepatic injury caused by an uncommon drug adverse reaction that can develop to conditions spanning from asymptomatic liver laboratory abnormalities to acute liver failure (ALF) and death. The cellular and molecular mechanisms involved in DILI are poorly understood. Hepatocyte damage can be caused by the metabolic activation of chemically active intermediate metabolites that covalently bind to macromolecules (e.g., proteins, DNA), forming protein adducts—neoantigens—that lead to the generation of oxidative stress, mitochondrial dysfunction, and endoplasmic reticulum (ER) stress, which can eventually lead to cell death. In parallel, damage-associated molecular patterns (DAMPs) stimulate the immune response, whereby inflammasomes play a pivotal role, and neoantigen presentation on specific human leukocyte antigen (HLA) molecules trigger the adaptive immune response. A wide array of antioxidant mechanisms exists to counterbalance the effect of oxidants, including glutathione (GSH), superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPX), which are pivotal in detoxification. These get compromised during DILI, triggering an imbalance between oxidants and antioxidants defense systems, generating oxidative stress. As a result of exacerbated oxidative stress, several danger signals, including mitochondrial damage, cell death, and inflammatory markers, and microRNAs (miRNAs) related to extracellular vesicles (EVs) have already been reported as mechanistic biomarkers. Here, the status quo and the future directions in DILI are thoroughly discussed, with a special focus on the role of oxidative stress and the development of new biomarkers. Full article

Methionine sulfoxide reductase (Msr) is a family of enzymes that reduces oxidized methionine and plays an important role in the survival of bacteria under oxidative stress conditions. MsrA and MsrB exist in a fusion protein form (MsrAB) in some pathogenic bacteria, such as Helicobacter pylori (Hp), Streptococcus pneumoniae, and Treponema denticola. To understand the fused form instead of the separated enzyme at the molecular level, we determined the crystal structure of HpMsrAB^C44S/C318S at 2.2 Å, which showed that a linker region (Hpiloop, 193–205) between two domains interacted with each HpMsrA or HpMsrB domain via three salt bridges (E193-K107, D197-R103, and K200-D339). Two acetate molecules in the active site pocket showed an sp² planar electron density map in the crystal structure, which interacted with the conserved residues in fusion MsrABs from the pathogen. Biochemical and kinetic analyses revealed that Hpiloop is required to increase the catalytic efficiency of HpMsrAB. Two salt bridge mutants (D193A and E199A) were located at the entrance or tailgate of Hpiloop. Therefore, the linker region of the MsrAB fusion enzyme plays a key role in the structural stability and catalytic efficiency and provides a better understanding of why MsrAB exists in a fused form. Full article

In this study, blueberry and blackcurrant powder were chosen as the phenolic-rich enrichments for oat bran. A Rapid Visco Analyser was used to form blueberry and blackcurrant enriched oat pastes. An in vitro digestion process evaluated the changes of phenolic compounds and the in vitro antioxidant potential of extracts of pastes. The anthocyanidin profiles in the extracts were characterised by the pH differential method. The results showed that blueberry and blackcurrant powder significantly increased the content of phenolic compounds and the in vitro antioxidant capacity of pastes, while the total flavonoid content decreased after digestion compared to the undigested samples. Strong correlations between these bioactive compounds and antioxidant values were observed. Lipopolysaccharide-stimulated RAW264.7 macrophages were used to investigate the intracellular antioxidant activity of the extracts from the digested oat bran paste with 25% enrichment of blueberry or blackcurrant powder. The results indicated that the extracts of digested pastes prevented the macrophages from experiencing lipopolysaccharide (LPS)-stimulated intracellular reactive oxygen species accumulation, mainly by the Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2) signalling pathway. These findings suggest that the bioactive ingredients from blueberry and blackcurrant powder enhanced the in vitro and intracellular antioxidant capacity of oat bran pastes, and these enriched pastes have the potential to be utilised in the development of the functional foods. Full article

Atherothrombosis, a multifactorial and multistep artery disorder, represents one of the main causes of morbidity and mortality worldwide. The development and progression of atherothrombosis is closely associated with age, gender and a complex relationship between unhealthy lifestyle habits and several genetic risk factors. The imbalance between oxidative stress and antioxidant defenses is the main biological event leading to the development of a pro-oxidant phenotype, triggering cellular and molecular mechanisms associated with the atherothrombotic process. The pathogenesis of atherosclerosis and its late thrombotic complications involve multiple cellular events such as inflammation, endothelial dysfunction, proliferation of vascular smooth muscle cells (SMCs), extracellular matrix (ECM) alterations, and platelet activation, contributing to chronic pathological remodeling of the vascular wall, atheromatous plague formation, vascular stenosis, and eventually, thrombus growth and propagation. Emerging studies suggest that clotting activation and endothelial cell (EC) dysfunction play key roles in the pathogenesis of atherothrombosis. Furthermore, a growing body of evidence indicates that defective autophagy is closely linked to the overproduction of reactive oxygen species (ROS) which, in turn, are involved in the development and progression of atherosclerotic disease. This topic represents a large field of study aimed at identifying new potential therapeutic targets. In this review, we focus on the major role played by the autophagic pathway induced by oxidative stress in the modulation of EC dysfunction as a background to understand its potential role in the development of atherothrombosis. Full article

The objective of this narrative review is to provide updated evidence, based on data from experimental and clinical studies, of the prominent role of omega-3 polyunsaturated fatty acids (n-3 PUFAs) for a number of crucial mechanisms involved in counteracting cell damage induced by oxidative stress in eye diseases. This article is focused on the antioxidant and neuroprotective effects of docosahexaenoic acid (DHA), which have been assessed in different experimental models and clinical studies, particularly in proliferative diabetic retinopathy, age-related macular degeneration and glaucoma that are the most common eye diseases leading to severe vision loss. The mechanisms involved in the role of DHA in protecting human retinal pigment epithelial cells from oxidative stress as well as the interaction with glutathione (GSH) are also described. The review is intended to provide novel and salient findings supporting the rationale of the use of dietary supplementation with high-dose DHA (1050 mg/day) in the form of triglyceride as a potent antioxidant compound for improving the eye health. However, the overall clinical evidence for the use of dietary strategies based on supplementation with n-3 PUFAs in eye diseases linked to oxidative stress other than high-dose DHA triglyceride is both limited and inconsistent. Full article

Barley (Hordeum vulgare) accumulates phenolic compounds (PhCs), which play a key role in plant defense against environmental stressors as antioxidants or UV screening compounds. The influence of light and atmospheric CO₂ concentration ([CO₂]) on the accumulation and localization of PhCs in barley leaves was examined for two varieties with different tolerances to oxidative stress. PhC localization was visualized in vivo using fluorescence microscopy. Close relationships were found between fluorescence-determined localization of PhCs in barley leaves and PhC content estimated using liquid chromatography coupled with mass spectroscopy detection. Light intensity had the strongest effect on the accumulation of PhCs, but the total PhC content was similar at elevated [CO₂], minimizing the differences between high and low light. PhCs localized preferentially near the surfaces of leaves, but under low light, an increasing allocation of PhCs in deeper mesophyll layers was observed. The PhC profile was significantly different between barley varieties. The relatively tolerant variety accumulated significantly more hydroxycinnamic acids, indicating that these PhCs may play a more prominent role in oxidative stress prevention. Our research presents novel evidence that [CO₂] modulates the accumulation of PhCs in barley leaves. Mesophyll cells, rather than epidermal cells, were most responsive to environmental stimuli in terms of PhC accumulation. Full article

Emerging data demonstrate the important roles of altered gut microbiomes (dysbiosis) in many disease states in the peripheral tissues and the central nervous system. Gut dysbiosis with decreased ratios of Bacteroidetes/Firmicutes and other changes are reported to be caused by many disease states and various environmental factors, such as ethanol (e.g., alcohol drinking), Western-style high-fat diets, high fructose, etc. It is also caused by genetic factors, including genetic polymorphisms and epigenetic changes in different individuals. Gut dysbiosis, impaired intestinal barrier function, and elevated serum endotoxin levels can be observed in human patients and/or experimental rodent models exposed to these factors or with certain disease states. However, gut dysbiosis and leaky gut can be normalized through lifestyle alterations such as increased consumption of healthy diets with various fruits and vegetables containing many different kinds of antioxidant phytochemicals. In this review, we describe the mechanisms of gut dysbiosis, leaky gut, endotoxemia, and fatty liver disease with a specific focus on the alcohol-associated pathways. We also mention translational approaches by discussing the benefits of many antioxidant phytochemicals and/or their metabolites against alcohol-mediated oxidative stress, gut dysbiosis, intestinal barrier dysfunction, and fatty liver disease. Full article

Cardiovascular disease is the leading cause of death in the U.S. While various studies have shown the beneficial impact of exogenous hydrogen sulfide (H₂S)-releasing drugs, few have demonstrated the influence of endogenous H₂S production. Modulating the predominant enzymatic sources of H₂S—cystathionine-β-synthase, cystathionine-γ-lyase, and 3-mercaptopyruvate sulfurtransferase—is an emerging and promising research area. This review frames the discussion of harnessing endogenous H₂S within the context of a non-ischemic form of cardiomyopathy, termed diabetic cardiomyopathy, and heart failure. Also, we examine the current literature around therapeutic interventions, such as intermittent fasting and exercise, that stimulate H₂S production. Full article

This review aims to pin out the importance of developing a technique for rapid detection of antioxidants, based on molecular imprinting techniques. It covers three major areas that have made great progress over the years in the field of research, namely: antioxidants characterization, molecular imprinting and electrochemistry, alone or combined. It also reveals the importance of bringing these three areas together for a good evaluation of antioxidants in a simple or complex medium, based on selectivity and specificity. Although numerous studies have associated antioxidants with molecular imprinting, or antioxidants with electrochemistry, but even electrochemistry with molecular imprinting to valorize different compounds, the growing prominence of antioxidants in the food, medical, and paramedical sectors deserves to combine the three areas, which may lead to innovative industrial applications with satisfactory results for both manufacturers and consumers. Full article

Nowadays, more and more young people want to experience illegal, psychoactive substances, without knowing the risks of exposure. Besides affecting social life, psychoactive substances also have an important effect on consumer health. We summarized and analyzed the published literature data with reference to the mechanism of free radical generation and the link between chemical structure and oxidative stress related to dopaminergic neurotransmission. This review presents data on the physicochemical properties, on the ability to cross the blood brain barrier, the chemical structure activity relationship (SAR), and possible mechanisms by which neuronal injuries occur due to oxidative stress as a result of drug abuse such as “bath salts”, amphetamines, or cocaine. The mechanisms of action of ingested compounds or their metabolites involve intermediate steps in which free radicals are generated. The brain is strongly affected by the consumption of such substances, facilitating the induction of neurodegenerative diseases. It can be concluded that neurotoxicity is associated with drug abuse. Dependence and oxidative stress are linked to inhibition of neurogenesis and the onset of neuronal death. Understanding the pathological mechanisms following oxidative attack can be a starting point in the development of new therapeutic targets. Full article