Genes da instabilidade de microssatélites no câncer colorretal: papel na inflamação e estresse oxidativo / Microsatellite instability genes in colorectal cancer: role in inflammation and oxidative stress

A instabilidade de microssatélites é um fenômeno genético caracterizado pela alteração na repetição de sequências de nucleotídeos conhecidas como microssatélites. Esta instabilidade pode ocorrer devido a defeitos nos genes reparadores de DNA, como os genes MLH1, MSH2, MSH6 e PMS2. A inflamação crônica tem sido associada ao desenvolvimento do câncer colorretal. Os genes da instabilidade de microssatélites estão envolvidos na regulação da resposta inflamatória, podendo influenciar a progressão tumoral. Estudos demonstraram que a presença de instabilidade de microssatélites em tumores colorretais está relacionada a uma maior infiltração de células imunes, como linfócitos T, macrófagos e neutrófilos, que podem modular a resposta inflamatória no microambiente tumoral. O estresse oxidativo é caracterizado pelo desequilíbrio entre a produção de espécies reativas de oxigênio e a capacidade antioxidante do organismo e desempenha um papel importante na carcinogênese. Os genes da instabilidade de microssatélites podem influenciar a resposta ao estresse oxidativo, afetando a capacidade das células tumorais de lidar com o dano oxidativo e promovendo a sobrevivência celular. O objetivo deste trabalho consiste na compreensão dos genes envolvidos na instabilidade de microssatélites no câncer colorretal e como eles contribuem para o desenvolvimento da doença, relacionando com processos inflamatórios e estresse oxidativo nas células tumorais. Justifica-se pela necessidade de compreensão das interconexões entre a instabilidade de microssatélites, inflamação e o estresse oxidativo em pacientes com câncer colorretal.

Microsatellite instability is a genetic phenomenon characterized by changes in the repetition of nucleotide sequences known as microsatellites. This instability may occur due to defects in DNA repair genes, such as the MLH1, MSH2, MSH6 and PMS2 genes. Chronic inflammation has been linked to the development of colorectal cancer. Microsatellite instability genes are involved in regulating the inflammatory response and may influence tumor progression. Studies have shown that the presence of microsatellite instability in colorectal tumors is related to a greater infiltration of immune cells, such as T lymphocytes, macrophages and neutrophils, which can modulate the inflammatory response in the tumor microenvironment. Oxidative stress is characterized by the imbalance between the production of reactive oxygen species and the body's antioxidant capacity and plays an important role in carcinogenesis. Microsatellite instability genes can influence the response to oxidative stress, affecting the ability of tumor cells to deal with oxidative damage and promoting cell survival. The objective of this work is to understand the genes involved in microsatellite instability in colorectal cancer and how they contribute to the development of the disease, relating it to inflammatory processes and oxidative stress in tumor cells. It is justified by the need to understand the interconnections between microsatellite instability, inflammation and oxidative stress in patients with colorectal cancer.

Morphological and Morphometric Analysis, Apoptosis and Oxidative Stress Study in Hep 2 Cells Treated by Resveratrol or Quercetine / Análisis Morfológico y Morfométrico, Estudio de Apoptosis y Estrés Oxidativo en Células Hep 2 Tratadas con Resveratrol o Quercetina

SUMMARY: Resveratrol (RES) and quercetine (QRC), is a promising agent relevant for both cancer chemoprevention and treatment via several signaling pathways, involved in their anticancer activity related to its chemotherapeutic potential, associated with the induction of ROS generation in cancer cells, leading to apoptosis. In our study, we have summarized the mechanisms of action of RES and QRC, and their pharmacological implications and potential therapeutic applications in cancer therapy. After treatment of Hep 2 cells with QRC or RES, the death pathways such as the cytochrome c release, ERK1/2 and IRS-1 pathways were upregulated, while cell survival pathway, including PI3K/AKT were downregulated. The RES and QRC caused oncosis, cells hypertrophy, hypercondensatin of chromatin, rupture of the plasma membrane and nuclear membrane, and formation of apoptotic bodies. Morphometric measurements of some cellular and nuclear parameters showed that RES and QRC induced an increase in cells and nuclear size, the nucleocytoplasmic ratio remained below 1 (N-Cyt R < 1), sign of low nuclear activity. The RES and QRC induced apoptosis of Hep2 cells by increasing of oxidative stress markers, MDA, and by modulating detoxifying enzymes, CAT and SOD. Our study results prove antiproliferative and proapoptotic properties of quercetin and resveratrol with regard to larynx cancer.

Resveratrol (RES) y quercetina (QRC), es un agente prometedor y relevante tanto para la quimioprevención como para el tratamiento del cáncer a través de varias vías de señalización, involucrado en su actividad anticancerígena relacionada con su potencial quimioterapéutico, asociado con la inducción de la generación de especies reactivas del oxígeno (ROS) en células cancerosas, lo que lleva a apoptosis. En nuestro estudio, hemos resumido los mecanismos de acción de RES y QRC, y sus implicaciones farmacológicas y posibles aplicaciones terapéuticas en la terapia del cáncer. Después del tratamiento de las células Hep 2 con QRC o RES, las vías de muerte, tal como la liberación de citocromo c, las vías ERK1/2 e IRS-1, se regulaban positivamente, mientras que la vía de supervivencia celular, incluida PI3K/AKT, se regulaba negativamente. El RES y el QRC provocaron oncosis, hipertrofia celular, hipercondensación de la cromatina, rotura de la membrana plasmática y nuclear y formación de cuerpos apoptóticos. Las mediciones morfométricas de algunos parámetros celulares y nucleares mostraron que RES y QRC indujeron un aumento en las células y el tamaño nuclear, la proporción nucleocitoplasmática se mantuvo por debajo de 1 (N- Cyt R <1), signo de baja actividad nuclear. RES y QRC indujeron la apoptosis de las células Hep2 aumentando los marcadores de estrés oxidativo, MDA, y modulando las enzimas desintoxicantes, CAT y SOD. Los resultados de nuestro estudio demuestran las propiedades antiproliferativas y proapoptóticas de la quercetina y el resveratrol con respecto al cáncer de laringe.

Liver response to the consumption of fried sunflower oil.

Sunflower oil is one of the most commonly used fat sources in Argentina, and deep-fat frying is the popular food preparation process. The liver response of feeding a diet containing fried sunflower oil (SFOx) on growing rats was studied. Thirty-nine male weanling Wistar rats were randomly assigned to one of three diets for 8 wks: control (C), sunflower oil (SFO), and a diet containing SFOx, both of the sunflower diets were mixed with a commercial rat chow at weight ratio of 13% (w/w). Body weight and food consumption were recorded weekly. At t=8 wk, lipid profile and glycemia were measured. Visceral adiposity was registered. Liver was weighed and preserved for histological analysis, relative fatty acid profile, fibrosis markers and oxidative status. The three diets did not alter body weights; however, the SFOx fed rats showed increased energy intake and visceral fat; therefore, in liver saturated fat content, trans fatty acids, plus other unidentified minor components, such as hydroperoxides, hydroxides, epidioxides, hydroperoxy epidioxides, hydroxylepidioxides, and epoxides, were detected. The hepatosomatic index of SFOx rats was altered and showed hepatic steatosis. SFOx rats exhibited increased liver dichlorodihydrofluorescein-diacetate and thiobarbituric acid substance levels and oxidized-proteins content. Their livers had lower relative levels of monounsaturated, polyunsaturated fatty acids and catalase activity, but matrix metalloproteinase-9 activity was unchanged. Consumption of a diet rich in fried oil during growth could induce liver damage due to steatosis, excessive lipid toxicity and the accumulation of reactive oxygen species. Further progression could lead to hepatic fibrosis.

Endothelin-1 down-regulates nuclear factor erythroid 2-related factor-2 and contributes to perivascular adipose tissue dysfunction in obesity.

Perivascular adipose tissue (PVAT) negatively regulates vascular muscle contraction. However, in the context of obesity, the PVAT releases vasoconstrictor substances that detrimentally affect vascular function. A pivotal player in this scenario is the peptide endothelin-1 (ET-1), which induces oxidative stress and disrupts vascular function. The present study postulates that obesity augments ET-1 production in the PVAT, decreases the function of the nuclear factor erythroid 2-related factor-2 (Nrf2) transcription factor, further increasing reactive oxygen species (ROS) generation, culminating in PVAT dysfunction. Male C57BL/6 mice were fed either a standard or a high-fat diet for 16 weeks. Mice were also treated with saline or a daily dose of 100 mg·kg-1 of the ETA and ETB receptor antagonist Bosentan, for 7 days. Vascular function was evaluated in thoracic aortic rings, with and without PVAT. Mechanistic studies utilized PVAT from all groups and cultured WT-1 mouse brown adipocytes. PVAT from obese mice exhibited increased ET-1 production, increased ECE1 and ETA gene expression, loss of the anticontractile effect, as well as increased ROS production, decreased Nrf2 activity, and downregulated expression of Nrf2-targeted antioxidant genes. PVAT of obese mice also exhibited increased expression of Tyr216-phosphorylated-GSK3ß and KEAP1, but not BACH1 - negative Nrf2 regulators. Bosentan treatment reversed all these effects. Similarly, ET-1 increased ROS generation and decreased Nrf2 activity in brown adipocytes, events mitigated by BQ123 (ETA receptor antagonist). These findings place ET-1 as a major contributor to PVAT dysfunction in obesity and highlight that pharmacological control of ET-1 effects restores PVAT's cardiovascular protective role.

Tributyltin-induced visceral adiposity is associated with impaired redox balance in white adipose tissue of male rats.

Tributyltin (TBT) is an organotin compound that has several adverse health effects, including the development of obesity. Although obesity is strongly associated with adipose redox imbalance, there is a lack of information on whether TBT promotes a pro-oxidative environment in WAT. Thus, adult male Wistar rats were randomly exposed to either vehicle (ethanol 0.4%) or TBT (1000 ng/kg) for 30 days. Body and fat pad masses, visceral fat morphology, lipid peroxidation, protein carbonylation, redox status markers, and catalase activity were evaluated. TBT promoted increased adiposity and visceral fat, with hypertrophic adipocytes, but did not alter body mass and subcutaneous fat. ROS production and lipid peroxidation were elevated in TBT group, as well as catalase protein expression and activity, although protein oxidation and glutathione peroxidase protein expression remained unchanged. In conclusion, this is the first study to demonstrate that subacute TBT administration leads to visceral adipose redox imbalance, with increased oxidative stress. This enlights the understanding of the metabolic toxic outcomes of continuous exposure to TBT in mammals.

Polysaccharides extracted from tucum-do-cerrado fruits (Bactris setosa Mart) have antineoplastic effects in mice while preserving hepatic gluconeogenesis.

This study investigated the antitumoral, anti-inflammatory and oxidative effects of polysaccharides from tucum (Bactris setosa, TUC) using the Ehrlich carcinoma as a tumor model. Additionally, the glycogen content, cytochrome P levels, and gluconeogenesis from lactate were assessed in the liver of healthy animals. Tumor-bearing female mice were orally treated with 50 and 100 mg.kg-1 of TUC or vehicle, once a day, or with 1.5 mg.kg-1 methotrexate via i.p., every 3 days, along 21 days. Both doses of TUC reduced the tumor weight and volume. In the tumor tissue, it decreased GSH and IL-1ß levels, and increased LPO, NAG, NO and TNF-α levels. The tumor histology showed necrosis and leukocytes infiltration. The metabolic effects of TUC were investigated by measurement of total cytochrome P (CYP) and glycogen in tumor-bearing mice, and by ex vivo liver perfusion on non-bearing tumor male mice, using lactate as gluconeogenic precursor. Metabolically, the hepatic glucose and pyruvate productions, oxygen uptake, and the total CYP concentration were not modified by TUC. Thus, tucum-do-cerrado polysaccharides have antitumor effects through the modulation of oxidative stress and inflammation, without impairing glucose production from lactate in the liver, the main organ responsible for the metabolism of organic and xenobiotic compounds.

Neurodevelopmental changes in Drosophila melanogaster are restored by treatment with lutein-loaded nanoparticles: Positive modulation of neurochemical and behavioral parameters.

Neurodevelopmental disorders, such as autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD), are characterized by persistent changes in communication and social interaction, as well as restricted and stereotyped patterns of behavior. The complex etiology of these disorders possibly combines the effects of multiple genes and environmental factors. Hence, exposure to insecticides such as imidacloprid (IMI) has been used to replicate the changes observed in these disorders. Lutein is known for its anti-inflammatory and antioxidant properties and is associated with neuroprotective effects. Therefore, the aim of this study was to evaluate the protective effect of lutein-loaded nanoparticles, along with their mechanisms of action, on Drosophila melanogaster offspring exposed to IMI-induced damage. To simulate the neurodevelopmental disorder model, flies were exposed to a diet containing IMI for 7 days. Posteriorly, their offspring were exposed to a diet containing lutein-loaded nanoparticles for a period of 24 h, and male and female flies were subjected to behavioral and biochemical evaluations. Treatment with lutein-loaded nanoparticles reversed the parameters of hyperactivity, aggressiveness, social interaction, repetitive movements, and anxiety in the offspring of flies exposed to IMI. It also protected markers of oxidative stress and cell viability, in addition to preventing the reduction of Nrf2 and Shank3 immunoreactivity. These results demonstrate that the damage induced by exposure to IMI was restored through treatment with lutein-loaded nanoparticles, elucidating lutein's mechanisms of action as a therapeutic agent, which, after further studies, can become a co-adjuvant in the treatment of neurodevelopmental disorders, such as ASD and ADHD.

From pathophysiology to practice: addressing oxidative stress and sperm DNA fragmentation in Varicocele-affected subfertile men.

Varicocele can reduce male fertility potential through various oxidative stress mechanisms. Excessive production of reactive oxygen species may overwhelm the sperm's defenses against oxidative stress, damaging the sperm chromatin. Sperm DNA fragmentation, in the form of DNA strand breaks, is recognized as a consequence of the oxidative stress cascade and is commonly found in the ejaculates of men with varicocele and fertility issues. This paper reviews the current knowledge regarding the association between varicocele, oxidative stress, sperm DNA fragmentation, and male infertility, and examines the role of varicocele repair in alleviating oxidative-sperm DNA fragmentation in these patients. Additionally, we highlight areas for further research to address knowledge gaps relevant to clinical practice.

Prolonged exposure to the synthetic glucocorticoid dexamethasone induces brain damage via oxidative stress and apoptotic response in adult Daniorerio.

Due to its extensive use as a painkiller, anti-inflammatory, and immune modulatory agent, as well as its effectiveness in treating severe COVID-19, dexamethasone, a synthetic glucocorticoid, has gained attention not only for its impact on public health but also for its environmental implications. Various studies have reported its presence in aquatic environments, including urban waters, surface samples, sediments, drinking water, and wastewater effluents. However, limited information is available regarding its toxic effects on nontarget aquatic organisms. Therefore, this study aimed to investigate the mechanism of toxicity underlying dexamethasone-induced brain damage in the bioindicator Danio rerio following long-term exposure. Adult zebrafish were treated with environmentally relevant concentrations of dexamethasone (20, 40, and 60 ng L-1) for 28 days. To elucidate the possible mechanisms involved in the toxicity of the pharmaceutical compound, we conducted a behavioral test battery (Novel Tank and Light and Dark tests), oxidative stress biomarkers, acetylcholinesterase enzyme activity quantification, histopathological analysis, and gene expression analysis using qRT-PCR (p53, bcl-2, bax, caspase-3, nrf1, and nrf2).The results revealed that the pharmaceutical compound could produce anxiety-like symptoms, increase the oxidative-induced stress response, decrease the activity of acetylcholinesterase enzyme, and cause histopathological alterations, including perineuronal vacuolization, granular and molecular layers deterioration, cell swallowing and intracellular spaces. The expression of genes involved in the apoptotic process (p53, bax, and casp-3) and antioxidant defense (nrf1 and nrf2) was upregulated in response to oxidative damage, while the expression of the anti-apoptotic gene bcl-2 was down-regulated indicating that the environmental presence of dexamethasone may pose a threat to wildlife and human health.

Changes in Noradrenergic Synthesis and Dopamine Beta-Hydroxylase Activity in Response to Oxidative Stress after Iron-induced Brain Injury.

Noradrenaline (NA) levels are altered during the first hours and several days after cortical injury. NA modulates motor functional recovery. The present study investigated whether iron-induced cortical injury modulated noradrenergic synthesis and dopamine beta-hydroxylase (DBH) activity in response to oxidative stress in the brain cortex, pons and cerebellum of the rat. Seventy-eight rats were divided into two groups: (a) the sham group, which received an intracortical injection of a vehicle solution; and (b) the injured group, which received an intracortical injection of ferrous chloride. Motor deficits were evaluated for 20 days post-injury. On the 3rd and 20th days, the rats were euthanized to measure oxidative stress indicators (reactive oxygen species (ROS), reduced glutathione (GSH) and oxidized glutathione (GSSG)) and catecholamines (NA, dopamine (DA)), plus DBH mRNA and protein levels. Our results showed that iron-induced brain cortex injury increased noradrenergic synthesis and DBH activity in the brain cortex, pons and cerebellum at 3 days post-injury, predominantly on the ipsilateral side to the injury, in response to oxidative stress. A compensatory increase in contralateral noradrenergic activity was observed, but without changes in the DBH mRNA and protein levels in the cerebellum and pons. In conclusion, iron-induced cortical injury increased the noradrenergic response in the brain cortex, pons and cerebellum, particularly on the ipsilateral side, accompanied by a compensatory response on the contralateral side. The oxidative stress was countered by antioxidant activity, which favored functional recovery following motor deficits.

Impact of intravascular hemolysis on functional and molecular alterations in the urinary bladder: implications for an overactive bladder in sickle cell disease.

Patients with sickle cell disease (SCD) display an overactive bladder (OAB). Intravascular hemolysis in SCD is associated with various severe SCD complications. However, no experimental studies have evaluated the effect of intravascular hemolysis on bladder function. This study aimed to assess the effects of intravascular hemolysis on the micturition process and the contractile mechanisms of the detrusor smooth muscle (DSM) in a mouse model with phenylhydrazine (PHZ)-induced hemolysis; furthermore, it aimed to investigate the role of intravascular hemolysis in the dysfunction of nitric oxide (NO) signaling and in increasing oxidative stress in the bladder. Mice underwent a void spot assay, and DSM contractions were evaluated in organ baths. The PHZ group exhibited increased urinary frequency and increased void volumes. DSM contractile responses to carbachol, KCl, α-ß-methylene-ATP, and EFS were increased in the PHZ group. Protein expression of phosphorylated endothelial NO synthase (eNOS) (Ser-1177), phosphorylated neuronal NO synthase (nNOS) (Ser-1417), and phosphorylated vasodilator-stimulated phosphoprotein (VASP) (Ser-239) decreased in the bladder of the PHZ group. Protein expression of oxidative stress markers, NOX-2, 3-NT, and 4-HNE, increased in the bladder of the PHZ group. Our study shows that intravascular hemolysis promotes voiding dysfunction correlated with alterations in the NO signaling pathway in the bladder, as evidenced by reduced levels of p-eNOS (Ser-1177), nNOS (Ser-1417), and p-VASP (Ser-239). The study also showed that intravascular hemolysis increases oxidative stress in the bladder. Our study indicates that intravascular hemolysis promotes an OAB phenotype similar to those observed in patients and mice with SCD.

Nrf2 cell signaling pathway is responsible for the antioxidant effect of resveratrol in aging.

INTRODUCTION: One of the markers of aging is oxidative stress, a condition characterized by an increase in free radicals concomitant with a reduction in antioxidant defenses. Within this, resveratrol is a compound that has been shown to act as a potent antioxidant. However, few studies highlight the cellular signaling pathways that are activated or inhibited during aging and that are responsible for this biological effect. AIM: To verify the antioxidant profile of resveratrol (5 µM) in leukocytes from donors in different age groups. METHODS: The project was approved by the Ethics Committee. Individuals were divided into three groups: 20-39, 40-59, and 60-80 years old. After separating the leukocytes, assays were performed to evaluate the AMPK (AMP-activated protein kinase) and Nrf2 (erythroid nuclear factor 2-related factor 2) pathways. In addition, luciferase assay and enzyme-linked immunosorbent assay were performed to evaluate transcription factor activation and Nrf2 expression, respectively. The analysis between age and treatment was performed using Pearson correlation (*P < 0.05). RESULTS: There was a reduction in the antioxidant effect of resveratrol during the aging process. In leukocytes from donors over 60 years of age, the AMPK pathway was silenced. Nrf2 was active at all ages. There was an increase in the activation of the transcription factor and phosphorylated protein in all age groups. CONCLUSIONS: Nrf2 is an important biochemical mechanism responsible for the antioxidant effect of resveratrol. This effect diminishes with aging but is still observed. Geriatr Gerontol Int 2024; ••: ••-••.

Unraveling the rationale and conducting a comprehensive assessment of AdipoRon (adiponectin receptor agonist) as a candidate drug for diabetic nephropathy and cardiomyopathy prevention and intervention-a systematic review.

Type 2 diabetes mellitus (T2DM) is a widespread chronic disease characterized by persistent hyperglycemia, leading to severe complications such as diabetic cardiomyopathy and nephropathy, significantly affecting patient health and quality of life. The complex mechanisms underlying these complications include chronic inflammation, oxidative stress, and metabolic dysregulation. Diabetic cardiomyopathy, marked by structural and functional heart abnormalities, and diabetic nephropathy, characterized by progressive kidney damage, are major contributors to the increased morbidity and mortality associated with T2DM. AdipoRon, a synthetic adiponectin receptor agonist, has shown potential in preclinical studies for mimicking the beneficial effects of endogenous adiponectin, reducing inflammation and oxidative stress, and improving lipid metabolism and mitochondrial function. This systematic review evaluates the therapeutic potential of AdipoRon, focusing on its impact on diabetic cardiomyopathy and nephropathy. Through a comprehensive literature search and analysis, we highlight AdipoRon's role in ameliorating cardiovascular and renal complications in various animal models and cellular systems. The findings underscore the urgent need for translational clinical studies to validate AdipoRon's efficacy and safety in human populations, aiming to advance this promising therapeutic approach from experimental models to clinical application, potentially offering new hope for improved management of diabetic complications.

Brazil nuts potential: effects on lipid peroxidation and heart health in nephrectomized rats.

OBJECTIVES: To investigate the effects of a Brazil nut-enriched diet on the wall thickness and the left ventricular chamber diameter of the heart, and lipid peroxidation in a CKD-induced model. METHODS: Male Wistar rats at 12 weeks of age were divided into two groups (n=16/group): the Nx group, which underwent 5/6 nephrectomy, and the Sham group, as a control. After 5 weeks, the groups were subdivided according to diet (n=8/group): the Nx and Sham groups received a control diet; the Nx5% and Sham5% groups received a diet enriched with 5 % Brazil nuts for 8 weeks. The left ventricular thickening and chamber diameter were determined. Plasma biochemical parameters were evaluated. Analysis of thiobarbituric acid reactive substances (TBARS) and antioxidant enzyme activity was performed in the plasma and the left ventricle (LV). LV mRNA expression of nuclear factor-kappa B (NF-κB) and nuclear factor erythroid 2-related factor 2 (Nrf2) was evaluated by reverse transcription-polymerase chain reaction. RESULTS: The Nx5% group showed a remodeled LV wall with decreased thickness compared to the Nx group (p=0.016). Furthermore, LV TBARS concentration was reduced in the Nx5% group (p=0.0064). In addition, the Nx5% group showed an increase in plasma GPx activity (p=0.0431). No significant results were found concerning the LV mRNA expression of NF-κB and Nrf2 genes. CONCLUSIONS: A Brazil nut-enriched diet decreased LV thickness and LV TBARS concentration and increased GPx activity in a 5/6 nephrectomy experimental model, making it a promising adjuvant therapy to improve antioxidant status and cardiovascular outcomes in chronic kidney disease.

Aesthetic Radiofrequency Associated with Rosmarinus officinalis Supplementation is Safe and Reduces Oxidative Stress in Women: Randomized, and Double-Blind Clinical Trial.

The objective were to evaluate the effects of supplementation of standardized dry extract of Rosmarinus officinalis (RO) and the application of aesthetic radiofrequency on the oxidative stress markers catalase (CAT), superoxide dismutase (SOD), non-protein thiols (NP-SH), and thiobarbituric acid reactive species (TBARS) and the biochemical markers triglycerides, total cholesterol, high density lipoprotein (HDL) cholesterol, glutamic-oxaloacetic transaminase (TGO/AST), pyruvic-glutamic transaminase (TGP/ALT), gamma glutamyl transpeptidase (gamma-GT), and creatinine. This study included 32 women received the aesthetic therapy to reduce localized fat. They were divided into the control group (n = 8) receiving placebo capsules and the intervention group (n = 24) subdivided into Group A, B, and C, each with eight members receiving supplementation with 100, 500, and 1000 mg/day of standardized dry extract of RO, respectively. The Universal Trial Number (UTN) - U1111-1274-6255. Supplementation with RO (500 mg/day) demonstrated a reduction in oxidative stress (quantified with through a significant increase in NP-SH and a reduction in SOD and CAT enzymes). The radiofrequency aesthetic treatment did not promote an increase in oxidative stress; however, it caused significant changes in total cholesterol, HDL cholesterol, and creatinine. RO is a plant with antioxidant effects and its oral consumption is safe in selected women subjects in hepatic and renal markers.

The impact of settleable atmospheric particulate on the energy metabolism, biochemical processes, and behavior of a sentinel mangrove crab.

We use the sentinel mangrove crab, Minuca rapax, as a model to investigate the effects of metallic settleable particulate matter (SePM) on wetland. Multiple levels of energetic responses, including (i) metabolic rate and energy budget, (ii) oxidative stress, and (iii) behavioral response by righting time, were assessed as well as the metal and metalloid content in crabs exposed to 0, 0.1 and 1 g.L-1 of SePM, under emerged and submerged conditions over five days, simulating the rigors of the intertidal habitat. Al, Fe, Mn, Cr, and Y exhibited a concentration-dependent increase. Metal concentrations were higher in submerged crabs due to the continuous ingestion of SePM and direct exposure through gills. Exposure concentration up to 1 g.L-1 decreased metabolic rate and enzymatic activities, reduced assimilation efficiency and energy for maintenance, and induces a slower response to righting time, probably by metal effects on nervous system and energy deficits. In conclusion, SePM exposure affects the redox status and physiology of M. rapax depending on he submersion regime and SePM concentration. The disruption to the energy budget and the lethargic behavior in M. rapax exposed to SePM implies potential ecological alterations in the mangrove ecosystem with unknown consequences for the local population.

Nebulized Glutathione as a Key Antioxidant for the Treatment of Oxidative Stress in Neurodegenerative Conditions.

Glutathione (GSH), a tripeptide synthesized intracellularly, serves as a pivotal antioxidant, neutralizing reactive oxygen species (ROS) and reactive nitrogen species (RNS) while maintaining redox homeostasis and detoxifying xenobiotics. Its potent antioxidant properties, particularly attributed to the sulfhydryl group (-SH) in cysteine, are crucial for cellular health across various organelles. The glutathione-glutathione disulfide (GSH-GSSG) cycle is facilitated by enzymes like glutathione peroxidase (GPx) and glutathione reductase (GR), thus aiding in detoxification processes and mitigating oxidative damage and inflammation. Mitochondria, being primary sources of reactive oxygen species, benefit significantly from GSH, which regulates metal homeostasis and supports autophagy, apoptosis, and ferroptosis, playing a fundamental role in neuroprotection. The vulnerability of the brain to oxidative stress underscores the importance of GSH in neurological disorders and regenerative medicine. Nebulization of glutathione presents a novel and promising approach to delivering this antioxidant directly to the central nervous system (CNS), potentially enhancing its bioavailability and therapeutic efficacy. This method may offer significant advantages in mitigating neurodegeneration by enhancing nuclear factor erythroid 2-related factor 2 (NRF2) pathway signaling and mitochondrial function, thereby providing direct neuroprotection. By addressing oxidative stress and its detrimental effects on neuronal health, nebulized GSH could play a crucial role in managing and potentially ameliorating conditions such as Parkinson's Disease (PD) and Alzheimer's Disease (AD). Further clinical research is warranted to elucidate the therapeutic potential of nebulized GSH in preserving mitochondrial health, enhancing CNS function, and combating neurodegenerative conditions, aiming to improve outcomes for individuals affected by brain diseases characterized by oxidative stress and neuroinflammation.

Associations of oxidative stress markers with the prevalence of sarcopenia in the United States general population.

OBJECTIVE: The purpose of the present study was to examine the association of oxidative stress markers with sarcopenia in the general United States population under the age of 60. METHODS: We used the National Health and Nutrition Examination Survey data from 2011‒2014 and performed Restricted Cubic Spline (RCS) plots, weighted multivariable logistic regression analysis to calculate ratio ratios and 95% Confidence Intervals, and subgroup analysis based on age, sex, hypertension, diabetes mellitus, and body mass index stratification to determine the association of markers of oxidative stress with the prevalence of sarcopenia. RESULTS: The present analysis included a total of 8,782 participants. Firstly, the RCS plots showed a roughly L-shaped curve association of total bilirubin and serum iron with a prevalence of sarcopenia. Secondly, albumin was negatively and linearly associated with the risk of sarcopenia. Finally, with the increase in gamma-glutamyl transferase, the prevalence of sarcopenia showed a trend of first rising and then declining as a result of the iron increase. CONCLUSIONS: We demonstrated a nonlinear association between markers of oxidative stress and sarcopenia. The need to focus more on levels of oxidative stress in the body could provide better prevention strategies for sarcopenia.

New insights into the pro-oxidant mechanism of dehydroleucodine on Trypanosoma cruzi.

Chagas disease, caused by Trypanosoma cruzi (T. cruzi), is one of the most important neglected diseases in Latin America. The limited use of the current nitro-derivative-based chemotherapy highlights the need for alternative drugs and the identification of their molecular targets. In this study, we investigated the trypanocidal effect of the sesquiterpene lactone dehydroleucodine (DhL) and its derivatives, focusing on the antioxidative defense of the parasites. DhL and two derivatives, at lesser extent, displayed antiproliferative effect on the parasites. This effect was blocked by the reducing agent glutathione (GSH). Treated parasites exhibited increased intracellular ROS concentration and trypanothione synthetase activity, accompanied by mitochondrial swelling. Although molecular dynamics studies predicted that GSH would not interact with DhL, 1H-NMR analysis confirmed that GSH could protect parasites by interacting with the lactone. When parasites overexpressing mitochondrial tryparedoxin peroxidase were incubated with DhL, its effect was attenuated. Overexpression of cytosolic tryparedoxin peroxidase also provided some protection against DhL. These findings suggest that DhL induces oxidative imbalance in T. cruzi, offering new insights into potential drug targets against this parasite.

Effects of concurrent training and N-acetylcysteine supplementation on cardiac remodeling and oxidative stress in middle-aged spontaneously hypertensive rats.

BACKGROUND: This study evaluated the effects of concurrent isolated training (T) or training combined with the antioxidant N-acetylcysteine (NAC) on cardiac remodeling and oxidative stress in spontaneously hypertensive rats (SHR). METHODS: Six-month-old male SHR were divided into sedentary (S, n = 12), concurrent training (T, n = 13), sedentary supplemented with NAC (SNAC, n = 13), and concurrent training with NAC supplementation (TNAC, n = 14) groups. T and TNAC rats were trained three times a week on a treadmill and ladder; NAC supplemented groups received 120 mg/kg/day NAC in rat chow for eight weeks. Myocardial antioxidant enzyme activity and lipid hydroperoxide concentration were assessed by spectrophotometry. Gene expression of NADPH oxidase subunits Nox2, Nox4, p22 phox, and p47 phox was evaluated by real time RT-PCR. Statistical analysis was performed using ANOVA and Bonferroni or Kruskal-Wallis and Dunn. RESULTS: Echocardiogram showed concentric remodeling in TNAC, characterized by increased relative wall thickness (S 0.40 ± 0.04; T 0.39 ± 0.03; SNAC 0.40 ± 0.04; TNAC 0.43 ± 0.04 *; * p < 0.05 vs T and SNAC) and diastolic posterior wall thickness (S 1.50 ± 0.12; T 1.52 ± 0.10; SNAC 1.56 ± 0.12; TNAC 1.62 ± 0.14 * mm; * p < 0.05 vs T), with improved contractile function (posterior wall shortening velocity: S 39.4 ± 5.01; T 36.4 ± 2.96; SNAC 39.7 ± 3.44; TNAC 41.6 ± 3.57 * mm/s; * p < 0.05 vs T). Myocardial lipid hydroperoxide concentration was lower in NAC treated groups (S 210 ± 48; T 182 ± 43; SNAC 159 ± 33 *; TNAC 110 ± 23 *# nmol/g tissue; * p < 0.05 vs S, # p < 0.05 vs T and SNAC). Nox 2 and p22 phox expression was higher and p47 phox lower in T than S [S 1.37 (0.66-1.66); T 0.78 (0.61-1.04) *; SNAC 1.07 (1.01-1.38); TNAC 1.06 (1.01-1.15) arbitrary units; * p < 0.05 vs S]. NADPH oxidase subunits did not differ between TNAC, SNAC, and S groups. CONCLUSION: N-acetylcysteine supplementation alone reduces oxidative stress in untreated spontaneously hypertensive rats. The combination of N-acetylcysteine and concurrent exercise further decreases oxidative stress. However, the lower oxidative stress does not translate into improved cardiac remodeling and function in untreated spontaneously hypertensive rats.