Search Results (102)

Although emerging evidence suggests that epigenetic mechanisms contribute to the pathogenesis and progression of type 2 diabetes mellitus (T2DM), data remain limited for patients with suboptimal metabolic control. The aim of this study was to assess global DNA methylation in patients with poorly controlled T2DM and to identify diabetes-related factors associated with DNA methylation levels. The study included 107 patients and 50 healthy controls. Global DNA methylation (5mC) was measured by UHPLC-DAD method. Pro-oxidant and antioxidant biomarkers, advanced glycation end-products, high-sensitivity C-reactive protein (hsCRP) and complete blood count were determined and leukocyte indices calculated. Patients had a significantly lower 5mC than controls (3.56 ± 0.31% vs. 4.00 ± 0.68%; p < 0.001), with further reductions observed in those with longer disease duration and diabetic foot ulcers. Oxidative stress and inflammatory biomarkers were higher in the patient group. DNA hypomethylation was associated with a higher monocyte-to-lymphocyte ratio and hsCRP, pro-oxidant–antioxidant balance, ischemia-modified albumin, and advanced oxidation protein products levels. Conversely, 5mC levels showed positive correlations with total antioxidant status and total sulfhydryl groups. Principal component analysis identified five key factors: proinflammatory, pro-oxidant, aging, hyperglycemic, and antioxidant. The pro-oxidant factor emerged as the sole independent predictor of global DNA hypomethylation in T2DM (OR = 2.294; p = 0.027). Our results indicate that global DNA hypomethylation could be a biomarker of T2DM progression, reflecting the complex interactions between oxidative stress, inflammation, and epigenetic modifications in T2DM. Full article

In the present study, five novel dexketoprofen amide derivatives with a free carboxyl group in their side chains were synthesized. The in vivo anti-inflammatory potential of dexketoprofen derivatives was evaluated using a carrageenan-induced paw edema model of acute inflammation. Additionally, the local and systemic redox status in rats following acute administration of the compounds was assessed by measuring levels of pro-oxidative markers and the activity of antioxidant enzymes. Among the analyzed molecules, derivatives 2 and 4 exhibited the most potent in vivo anti-inflammatory activity, showing effects comparable to those of the parent compound dexketoprofen. In vitro results revealed that all newly synthesized compounds exhibited low inhibitory activity toward COX-1, whereas only compound 4 showed significant COX-2 inhibition. The stronger binding affinity of derivative 4 for COX-2 in comparison to other tested compounds is likely attributed to its ability to form multiple electrostatic interactions within the enzyme’s active site. Furthermore, compounds 2 and 5 demonstrated efficacy comparable to the parent drug in restoring redox balance, indicating their potential antioxidant properties under acute inflammatory conditions. The findings of this study underscore the therapeutic potential of the novel dexketoprofen amide derivatives as dual-function agents with the capacity to modulate both inflammatory responses and oxidative stress. Full article

This study evaluates the health of a captive colony of Hamadryas baboons at Ravenna Zoo Safari (Italy), focusing on oxidative stress markers and biometric data. Forty-eight individuals were assessed during routine veterinary procedures: males underwent vasectomy, and females were checked for pregnancy. Biometric data collected included body weight, body length, and genital measurements in males, while females were evaluated for reproductive status. Oxidative stress was measured using two tests that assess both harmful pro-oxidant levels and the body’s antioxidant defenses. Results showed no significant differences in oxidative stress levels between sexes, although males and females differed in body weight. Pregnant and postpartum females exhibited higher oxidative stress, likely due to the metabolic and hormonal demands of reproduction. This supports the idea that reproductive activity increases the production of reactive oxygen species, requiring stronger antioxidant responses. In males, correlations between body weight and genital measurements suggest these could help estimate age in the absence of birth records. No link was found between oxidative stress and body weight, indicating limited age-related effects on these markers. Overall, the study highlights the importance of monitoring oxidative stress in captive primates to better understand the effects of reproduction and aging, and to improve welfare and management practices. Full article

Background/Objectives: Epilepsy is a complex neurological disorder with a strong link to oxidative stress, which contributes to seizure susceptibility and neuronal damage. This study aims to investigate the effects of curcumin (Cur), sodium valproate (VPA), and mitocurcumin (MitoCur), a mitochondria-targeted curcumin, on behavioral and oxidative stress parameters in a zebrafish model of pentylenetetrazole (PTZ)-induced seizures. Methods: Adult zebrafish were exposed to two concentrations (0.25 and 0.5 µM for Cur and MitoCur; 0.25 and 0.5 mM for VPA). Behavioral assessments, including locomotion, spatial exploration, and directional movement, were conducted using EthoVision XT tracking software. Oxidative stress markers, including superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GPx), and total antioxidant status (TAS), were analyzed in brain homogenates. Results: Behavioral analyses indicated dose-dependent effects, with higher doses generally reducing activity. MitoCur at 0.25 µM enhanced antioxidant defenses and reduced oxidative damage, while higher doses exhibited a pro-oxidant shift. VPA at 0.25 mM improved TAS without significantly altering MDA levels. Conclusions: These findings emphasize the importance of dose optimization in antioxidant-based epilepsy treatments and highlight the potential of MitoCur as a targeted therapeutic option. Full article

Reactive oxygen species (ROS) play a key role in cancer progression and antitumor therapy. Glioblastoma is a highly heterogeneous tumor with different cell populations exhibiting various redox statuses. Elevated ROS levels in cancer cells promote tumor growth and simultaneously make them more sensitive to anticancer drugs, but further elevation leads to cell death and apoptosis. Meanwhile, various subsets of tumor cells, such a glioblastoma stem cells (GSC) or the cells in tumor microenvironment (TME), demonstrate adaptive mechanisms to excessive ROS production by developing effective antioxidant systems such as glutathione- and thioredoxin-dependent. GSCs demonstrate higher chemoresistance and lower ROS levels than other glioma cells, while TME cells create a pro-oxidative environment and have immunosuppressive effects. Both subpopulations have become an attractive target for developing therapies. Increased expression of thioredoxin reductase (TrxR) is often associated with tumor progression and poor patient survival. Various TrxR inhibitors have been investigated as potential anticancer therapies, including nitrosoureas, flavonoids and metallic complexes. Gold derivatives are irreversible inhibitors of TrxR. Among them, auranofin (AF), a selective TrxR inhibitor, has proven its effectiveness as a drug for the treatment of rheumatoid arthritis and its efficacy as an anticancer agent has been demonstrated in preclinical studies in vitro and in vivo. However, further clinical application of AF could be challenging due to the low solubility and insufficient delivery to glioblastoma. Different delivery strategies for hydrophobic drugs could be used to increase the concentration of AF in the brain. Combining different therapeutic approaches that affect the redox status of various glioma cell populations could become a new strategy for treating brain tumor diseases. Full article

Chronic kidney disease (CKD) is associated with a high incidence of cardiovascular disease (CVD) due to the accumulation of uremic toxins, altered redox state, and chronic systemic inflammation. This study aimed to analyze the relationship between the redox status of patients with CKD and the phenotype of microvesicles (MVs) subtypes, and cardiovascular events. The oxidative stress level of each participant was determined using an individualized OXY-SCORE. The relationship between pro-oxidant and antioxidant parameters and the expression of membrane markers in endothelial-derived microvesicles (EMVs) and platelet-derived microvesicles (PMVs) was established. Patients with advanced CKD (ACKD) and hemodialysis (HD) had a higher OXY-SCORE than healthy subjects (HS), whereas peritoneal dialysis (PD) patients had similar scores to HS. PD patients showed elevated PMVs and CD41 expression, whereas HD patients had higher EMVs and CD31 expression. Patients with ACKD had higher tissue factor (TF) expression in the PMVs and EMVs. TF expression was correlated with xanthine oxidase (XO) activity and was negatively correlated with antioxidant parameters. Patients with cardiovascular events show elevated TF. In conclusion, microvesicles and oxidative stress may serve as markers of cardiovascular risk in CKD, with TF expression in PMVs and EMVs being potential predictive and prognostic biomarkers of CVD. Full article

Red blood cells (RBCs) are a vital component of the body’s oxygen supply system. In addition to being pro-oxidants, they are also essential components of the body’s antioxidant defense mechanism. RBCs are susceptible to both endogenous and exogenous sources of oxidants. Oxyhemoglobin autoxidation is the primary source of endogenous RBC oxidant production, which produces superoxide radicals and hydrogen peroxide. Potent exogenous oxidants from other blood cells and the surrounding endothelium can also enter RBCs. Both enzymatic (like glutathione peroxidase) and non-enzymatic (like glutathione) mechanisms can neutralize oxidants. These systems are generally referred to as oxidant scavengers or antioxidants, and they work to neutralize these harmful molecules (i.e., oxidants). While their antioxidative capabilities are essential to their physiological functions and delivering oxygen to tissues, their pro-oxidant behavior plays a part in several human pathologies. The redox-related changes in RBCs can have an impact on their function and fate. The balance between pro-oxidants and antioxidants determines the oxidative status of cells, which affects signal transduction, differentiation, and proliferation. When pro-oxidant activity exceeds antioxidative capacity, oxidative stress occurs, leading to cytotoxicity. This type of stress has been linked to various pathologies, including hemolytic anemia. This review compiles the most recent literature investigating the connections between RBC redox biochemistry, antioxidants, and diverse disorders. Full article

Cannabinoids include both endogenous endocannabinoids and exogenous phytocannabinoids, such as cannabidiol (CBD), and have potential as therapeutic agents in cancer treatment due to their selective anticancer activities. CBD exhibits both antioxidant and pro-oxidant effects depending on its concentration and cell types. These properties allow CBD to influence oxidative stress responses and potentially enhance the efficacy of antitumor therapies. In this study, we treated U87MG glioma cells with low dose (1 μM) CBD and evaluated its molecular effects. Our findings indicate that CBD reduced cell viability by 20% (p < 0.05) through the alteration of mitochondrial membrane potential. The alteration of redox status by CBD caused an attempt to rescue mitochondrial functionality through nuclear localization of the GABP transcription factor involved in mitochondria biogenesis. Moreover, CBD treatment caused an increase in autophagic flux, as supported by the increase in Beclin-1 and the ratio of LC3-II/LC3-I. Due to mitochondria functionality alteration, pro-apoptotic proteins were induced without activating apoptotic effectors Caspase-3 or Caspase-7. The study of the transcription factor NRF2 and the ubiquitin-binding protein p62 expression revealed an increase in their levels in CBD-treated cells. In conclusion, low-dose CBD makes U87MG cells more vulnerable to cytotoxic effects, reducing cell viability and mitochondrial dynamics while increasing autophagic flux and redox systems. This explains the mechanisms by which glioma cells respond to CBD treatment. These findings highlight the therapeutic potential of CBD, suggesting that modulating NRF2 and autophagy pathways could represent a promising strategy for glioblastoma treatment. Full article

The use of biological plant protection products is promising for agriculture. In particular, chitosan-based biopesticides have become widespread for stimulating growth and protecting plants from a wide range of pathogens. Novochizol is a product obtained by intramolecular cross-linking of linear chitosan molecules and has a globular shape, which provides it with a number of advantages over chitosan. Novochizol has previously been shown to have a stimulating effect on the growth and development of common wheat (Triticum aestivum L.). However, the effect of this preparation on the protective mechanisms against rust diseases has not been studied before. Our studies have revealed the dose effect of the preparation on the development of stem rust of wheat. When treating plants with novochizol at a concentration of 0.125% four days before infection, the best results were obtained, namely: a stable reaction was observed and the number of pustules decreased. To identify critical points of the drug’s effect on the protective mechanism against stem rust, we used an adrenaline test, which allows for a quick assessment of the pro/antioxidant status of plant extracts. We also assessed the activity of the major antioxidant enzymes, peroxidase and catalase, using commercial kits and the Folin–Ciocalteu reaction to assess the concentration of phenolic compounds. As a result, two stages were identified in infected plants pretreated with novochizol: early (up to 10 h after inoculation), characterized by antioxidant activity, and late (10–244 h), with prooxidant activity. These stages correspond to two peaks of accumulation of reactive oxygen species (ROS) in response to pathogen infection. The first peak is associated with the accumulation of superoxide anion O₂−, which is converted into oxygen and hydrogen peroxide under the action of the enzyme SOD (superoxide dismutase). The second peak is associated with the accumulation of H₂O₂. Hydrogen peroxide performs a protective function leading to the death of pathogen mycelial cells. In comparison with infected plants without novochizol treatment, we found a decrease in the activity of catalase (an enzyme that breaks down H₂O₂) at both stages, as well as peroxidase in the interval from 10 to 144 h after inoculation. Also, an increase in the concentration of phenolic compounds was found in the treated infected plants. We suggest that these changes under the influence of pretreatment with novochizol contribute to enhancements in plant defense functions against stem rust. Taking into account the physicochemical advantages of novochizol over chitosan, which provide a very low effective dose of the drug, the obtained results indicate its promise and safety as a biological plant protection product. This work is a preliminary stage for an extended analysis of the effect of novochizol on plant immunity using biochemical and molecular genetic approaches. Full article

Polyphenols are powerful natural antioxidants with numerous biological activities. They change cell membrane permeability, interact with receptors, intracellular enzymes, and cell membrane transporters, and quench reactive oxygen species (ROS). Yarrowia lipolytica yeast, being similar to mammalian cells, can be used as a model to study their survival ability upon long-lasting cultivation, assaying the effect of dihydroquercetin polyphenol (DHQ). The complex assessment of the physiological features of the population assaying cell respiration, survival, ROS detection, and flow cytometry was used. Y. lipolytica showed signs of chronological aging by eight weeks of growth, namely a decrease in the cell number, and size, increased ROS generation, a decrease in colony-forming unit (CFU) and metabolic activity, and decreased respiratory rate and membrane potential. An amount of 150 µM DHQ decreased ROS generation at the 6-week growth stage upon adding an oxidant of 2,2′-azobis (2-amidinopropane) dihydrochloride (AAPH). Moreover, it decreased CFU at 1–4 weeks of cultivation, inhibited cell metabolic activity of the 24-h-old culture and stimulated that on 14–56 days of growth, induced the cell respiration rate in the 24-h-old culture, and blocked alternative mitochondrial oxidase at growth late stages. DHQ serves as a mild pro-oxidant on the first day of age-stimulating anti-stress protection. In the deep stationary stage, it can act as a powerful antioxidant, stabilizing cell redox status and reducing free radical oxidation in mitochondria. It provides a stable state of population. The hormetic effects of DHQ using lower eukaryotes of Y. lipolytica have been previously discussed, which can be used as a model organism for screening geroprotective compounds of natural origin. Full article

Background/Objectives: When prooxidants outweigh antioxidants, oxidative stress can occur, causing an accumulation of reactive oxygen species (ROS). This process can lead to cellular damage and plays a role in the development of numerous health conditions. This study aimed to investigate the cytoprotective effects on differentiated Caco-2 cells of hydrolysates derived from the red Californian worm (WH) and their fractions, identify the peptides responsible for this effect, and elucidate the mechanisms involved. Methods: The WH was obtained through hydrolysis with Alcalase 2.4 L and subsequently fractionated to two fractions (F > 3 kDa and F < 3 kDa) using a ceramic membrane with a molecular weight cutoff of 3 kDa. The peptides found in the F < 3 kDa fraction, demonstrating the highest cytoprotective activity, were then sequenced via liquid chromatography-mass spectrometry analysis (LC-MS/MS), and molecular docking was conducted to elucidate the underlying antioxidant mechanisms. Results: The hydrolysate of Eisenia foetida and its F < 3 kDa fraction exhibited no cytotoxicity, protected the cells from H₂O₂-induced oxidative stress (50% increase viability), preserved cell viability by restoring their redox status (ROS: 20% decrease, and glutathione (GSH): recovered to basal control levels) and cell cycle distribution, and decreased apoptosis (16%). Twenty-eight peptides were identified, with five showing antioxidant activity through stable interactions with myeloperoxidase (MPO) and Kelch-like ECH-associated protein 1 (Keap-1), KPEDWDDR being the peptide that presented the highest affinity with both molecules (−7.9 and −8.8 kCal/mol, respectively). Conclusions: These results highlight the WH as a potential source of bioactive peptides for the management of oxidative stress. Full article

Prostate cancer is the leading cause of cancer death in men. Some studies suggest that selenium Se (+4) may help prevent prostate cancer. Certain forms of Se (+4), such as Selol, have shown anticancer activity with demonstrated pro-oxidative effects, which can lead to cellular damage and cell death, making them potential candidates for cancer therapy. Our recent study in healthy mice found that Selol changes the oxidative–antioxidative status in blood and tissue. However, there are no data on the effect of Selol in mice with tumors, considering that the tumor itself influences this balance. This research investigated the impact of Selol on tumor morphology and oxidative–antioxidative status in blood and tumors, which may be crucial for the formulation’s effectiveness. Our study was conducted on healthy and tumor-bearing animal models, which were either administered Selol or not. We determined antioxidant enzyme activities (Se-GPx, GPx, GST, and TrxR) spectrophotometrically in blood and the tumor. Furthermore, we measured plasma prostate-specific antigen (PSA) levels, plasma and tumor malondialdehyde (MDA) concentration as a biomarker of oxidative stress, selenium (Se) concentrations and the tumor ORAC value. Additionally, we assessed the impact of Selol on tumor morphology and the expression of p53, BCL2, and Ki-67. The results indicate that treatment with Selol influences the morphology of tumor cells, indicating a potential role in inducing cell death through necrosis. Long-term supplementation with Selol increased antioxidant enzyme activity in healthy animals and triggered oxidative stress in cancer cells, activating their antioxidant defense mechanisms. This research pathway shows promise in understanding the anticancer effects of Selol. Selol appears to increase the breakdown of cancer cells more effectively in small tumors than in larger ones. In advanced tumors, it may accelerate tumor growth if used as monotherapy. Therefore, further studies are necessary to evaluate its efficacy either in combination therapy or for the prevention of recurrence. Full article

Background: women aging is a normal process of life; however, hormonal changes create an imbalance between prooxidants and antioxidants and could be measured as the antioxidant capability (AC) of an organism. Objective: to find the association between plasma AC levels, dietary intakes, and body composition in 18–64-year-old women living in the northeast of Mexico. Methods: A total of n = 514 women (18–64 years old) were grouped according to STRAW criteria as reproductive, menopausal transition, and postmenopausal. Anthropometrics, body mass index (BMI), weight–hip ratio (WHR), and weight–height ratio WHtR were determined, and percentage of body fat was analyzed by bioelectrical impedance. Dietary intake of macronutrients and vitamins A, E, and C were analyzed by a 3-day food recall. The AC status in plasma was analyzed by the ORAC_FL assay. Results: Plasma AC levels were higher in postmenopausal women (815 µmol TE/L), and menopausal transition women (806 µmol TE/L) than in reproductive women (633 µmol TE/L). BMI was overweight (>25 kg/m²) in all three groups. WHtR and WHR are above the healthy limit of 0.5 and 0.8, respectively for both menopausal transition and postmenopausal women. In reproductive women, negative relationships were calculated between plasma AC and age (Rho = −0.250, p = 0.007), BMI (Rho = −0.473, p < 0.001), WHtR (Rho = −0.563, p < 0.001), WHR (Rho = −0.499, p < 0.001), and % body fat (Rho = −0.396, p < 0.001). A negative association was determined between plasma AC and WHtR in reproductive women (B = −2.718, p = 0.026). No association resulted for those in menopausal transition, and a positive association was obtained between plasma AC and protein (B = 0.001, p = 0.024) and vitamin E (B = 0.003, p = 0.013) intakes in postmenopausal women. Conclusions: the antioxidant capability (AC) in plasma was lower in reproductive women, and anthropometric parameters marking decreased physical fitness were associated with decreased AC. Full article

Obesity and overweight pose significant risks to health, contributing to the prevalence of chronic conditions like type 2 diabetes mellitus (T2DM) and cardiovascular diseases (CVD). The current study aimed to assess the impact of a 6-year nutritional and lifestyle intervention on oxidative and inflammatory markers in individuals aged 55 to 75, specifically those at high risk of CVD. A study was carried out in a group of 80 participants with metabolic syndrome (MetS) residing in Mallorca, Spain, who underwent nutritional intervention based on a low-calorie Mediterranean diet (MedDiet) and promotion of physical activity. Before and after the intervention, several parameters including anthropometric data, haematological factors, blood pressure, and physical activity level were measured. Oxidative and inflammatory biomarkers in plasma were analysed. After the 6-year intervention, participants who managed to reduce their body mass index (BMI) had greater reductions in abdominal obesity, waist to heigh ratio (WHtR), diastolic blood pressure, and glucose levels, and increased high density protein cholesterol (HDL-c) compared to those who did not reduce BMI. This higher reduction in BMI was related to reduced energy intake and increased adherence to MedDiet, with greater polyphenol intake, and total physical activity (PA). Furthermore, improvements in oxidative stress and proinflammatory status were observed in participants who reduced their BMI. Significant reductions in the activity of the prooxidant enzyme, myeloperoxidase (MPO), levels of the lipid oxidation marker, malondialdehyde (MDA), and the proinflammatory chemokine, monocyte chemoattractant protein-1 (MCP-1,) were found in those who reduced their BMI. In contrast, participants who did not improve their BMI exhibited higher levels of proinflammatory markers such as MCP-1 and tumour necrosis factor α (TNFα), as well as increased activity of the antioxidant enzyme catalase (CAT). Current findings suggest that an effective way to reduce BMI is a hypocaloric MedDiet combined with tailored physical activity to improve oxidative stress and proinflammatory status, and potentially reducing the risk of CVD. Full article

The objective of this study was to modify a protein-rich by-product, generated during β-glucan production, to render it appropriate for incorporation into meat products. Additionally, the study sought to assess the quality of a prototype meat product containing oat additives, depending on its concentration. Through hydrolyzation, its solubility was enhanced, making it suitable for broader applications in food products. With an average protein content of 52% and fat content of 6%, the pure hydrolysate exhibited a notable ferric ion reduction, as well as metal chelating properties. In meat formulations, the hydrolysate was integrated at concentrations of 1%, 2%, and 3%, relative to the meat mass. Following cooking and subsequent storage for 21 days, assessments were conducted every 7 days to evaluate colour retention, texture, and oxidation status. At concentrations of 2% to 3% (equivalent to 2–3 g/100 g), the hydrolysate significantly enhanced colour stability, while concurrently fostering oxidation. Notably, cohesiveness and resilience were augmented, with no discernible impact on hardness. The application of oat protein hydrolysate, particularly at 2–3 g/100 g, serves as a viable strategy for enhancing colour stability in meat formulations. However, its pro-oxidative effects necessitate supplementation with antioxidants to mitigate potential deterioration in the final product. Full article