Antitumoral Activity of Cecropia Pachystachya Leaves Extract in Vitro and in Vivo Model of Rat Glioma: Brain and Blood Effects.

The aim of this study was to investigate the antiglioma effect of Cecropia pachystachya Trécul (CEC) leaves extract against C6 and U87 glioblastoma (GB) cells and in a rat preclinical GB model. The CEC extract reduced in vitro cell viability and biomass. In vivo, the extract decreased the tumor volume approximately 62%, without inducing systemic toxicity. The deficit in locomotion and memory and an anxiolytic-like behaviors induced in the GB model were minimized by CEC. The extract decreased the levels of reactive oxygen species, nitrites and thiobarbituric acid reactive substances and increased the activity of antioxidant enzymes in platelets, sera and brains of GB animals. The activity of NTPDases, 5'-nucleotidase and adenosine deaminase (ADA) was evaluated in lymphocytes, platelets and serum. In platelets, ATP and AMP hydrolysis was reduced and hydrolysis of ADP and the activity of ADA were increased in the control, while in CEC-treated animals no alteration in the hydrolysis of ADP was detected. In serum, the reduction in ATP hydrolysis was reversed by CEC. In lymphocytes, the increase in the hydrolysis of ATP, ADP and in the activity of ADA observed in GB model was altered by CEC administration. The observed increase in IL-6 and decrease in IL-10 levels in the serum of GB animals was reversed by CEC. These results demonstrate that CEC extract is a potential complementary treatment to GB, decreasing the tumor size, while modulating aspects of redox and purinergic systems.

Senolytics prevent age-associated changes in female mice brain.

PURPOSE: Considering that the combination of dasatinib and quercetin (D + Q) demonstrated a neuroprotective action, as well as that females experience a decline in hormonal levels during aging and this is linked to increased susceptibility to Alzheimer's disease, in this study we evaluated the effect of D + Q on inflammatory and oxidative stress markers and on acetylcholinesterase and Na+, K+-ATPase activities in brain of female mice. METHODS: Female C57BL/6 mice were divided in Control and D (5 mg/kg) + Q (50 mg/kg) treated. Treatment was administered via gavage for three consecutive days every two weeks starting at 30 days of age. The animals were euthanized at 6 months of age and at 14 months of age. RESULTS: Results indicate an increase in reactive species (RS), thiol content and lipid peroxidation followed by a reduction in nitrite levels and superoxide dismutase, catalase and glutathione S-transferase activity in the brain of control animals with age. D+Q protected against age-associated increase in RS and catalase activity reduction. Acetylcholinesterase activity was increased, while Na+, K+-ATPase activity was reduced at 14 months of age and D+Q prevented this reduction. CONCLUSION: These data demonstrate that D+Q can protect against age-associated neurochemical alterations in the female brain.

Responses and modulation of the white shrimp Litopenaeus vannamei glutathione peroxidases 2 and 4 during hypoxia, reoxygenation and GPx4 knock-down.

Glutathione peroxidases (GPxs) are important antioxidant enzymes that act at distinct levels of the antioxidant defense. In vertebrates, there are several glutathione peroxidase (GPx) isoforms with different cellular and tissue distribution, but little is known about their interrelationships. The shrimp Litopenaeus vannamei is the main crustacean cultivated worldwide. It is affected by environmental stressors, including hypoxia and reoxygenation that cause reactive oxygen species accumulation. Thus, the antioxidant response modulation is key for shrimp resilience. Recently, several GPx isoforms genes were identified in the L. vannamei genome sequence, but their functions are just beginning to be studied. As in vertebrates, shrimp GPx isoforms can present differences in their antioxidant responses. Also, there could be interrelationships among the isoforms that may influence their responses. We evaluated shrimp GPx2 and GPx4 expressions during hypoxia, reoxygenation, and GPx4 knock-down using RNAi for silencing, as well as the enzymatic activity of total GPx and GPx4. Also, glutathione content in hepatopancreas was evaluated. GPx2 and GPx4 presented similar expression patterns during hypoxia and reoxygenation. Their expressions decreased during hypoxia and were reestablished in reoxygenation at 6 h in non-silenced shrimp. GPx2 expression was down-regulated by GPx4 knock-down, suggesting that GPx4 affects GPx2 expression. Total GPx activity changed in hypoxia and reoxygenation at 6 h but not at 12 h, while GPx4 activity was not affected by any stressor. The GSH/GSSG ratio in hepatopancreas indicated that at early hours, the redox status remains well-modulated but at 12 h it is impaired by hypoxia and reoxygenation.

Behavioral, biochemical, and endocrine responses of zebrafish to 30-min exposure with environmentally relevant concentrations of imidacloprid-based insecticide.

The imidacloprid-based insecticides (IBIs) are among the most used insecticides worldwide, and chronic and acute toxic effects (days exposure protocols) have been reported in several species in studies of IBIs at lethal concentrations. However, there is little information on shorter time exposures and environmentally relevant concentrations. In this study, we investigated the effect of a 30-min exposure to environmentally relevant concentrations of IBI on the behavior, redox status, and cortisol levels of zebrafish. We showed that the IBI decreased fish locomotion and social and aggressive behaviors and induced an anxiolytic-like behavior. Furthermore, IBI increased cortisol levels and protein carbonylation and decreased nitric oxide levels. These changes were mostly observed at 0.013 and 0.0013 µg·L-1 of IBI. In an environmental context, these behavioral and physiological disbalances, which were immediately triggered by IBI, can impair the ability of fish to evade predators and, consequently, affect their survival.

Assessment of Oxidative Stress Biomarkers in Rat Blood.

Redox status assessments are time-consuming, require a large volume of samples and great reagent amounts, and are not adequately described for methodological reproducibility. Here, the objective was to standardize redox balance determination, based on previously described spectrophotometric tests in pregnant rats, to improve precision, time dispensed, and the volume of samples and reagents, while maintaining accuracy and adequate cost benefits. This protocol summarizes oxidative stress markers, which focus on spectrophotometric tests for the assessment of thiobarbituric acid-reactive substances, reduced thiol groups, and hydrogen peroxide, as well as the antioxidant activity of superoxide dismutase, glutathione peroxidase, and catalase in washed erythrocyte and serum samples from full-term pregnant rats. For non-pregnant rats and other species, it is necessary to standardize these determinations, especially the sample volume. All measurements were normalized by the estimated protein concentrations in each sample. To establish optimum conditions for the reproducibility of the proposed methods, we describe all changes made in each assay's steps based on the reference method reassessed for the new standardizations. Furthermore, the calculations of the concentrations or activities of each marker are presented. Thus, we demonstrate that the analysis of serum samples is easier and faster, but it is impossible to detect catalase activity. Furthermore, the proposed methods can be applied for redox balance determination, especially using smaller reagent amounts and lower sample volumes in lesser time without losing accuracy, as is required in obtaining samples during rat pregnancy.

Calcium Supplementation on Glucose Tolerance, Oxidative Stress, and Reproductive Outcomes of Diabetic Rats and Their Offspring.

Diabetes mellitus increases the risk of obstetric complications, morbidity, and infant mortality. Controlled nutritional therapy with micronutrients has been employed. However, the effect of calcium (Ca2+) supplementation on diabetic pregnancy is unclear. We aimed to evaluate whether diabetic rats supplemented with Ca2+ during pregnancy present better glucose tolerance, redox status, embryonic and fetal development, newborn weight, and the prooxidant and antioxidant balance of male and female pups. For this, newborn rats received the beta-cytotoxic drug streptozotocin for inducing diabetes on the day of birth. In adulthood, these rats were mated and treated with Ca2+ twice a day from day 0 to day 20 of pregnancy. On day 17, the pregnant rats were submitted to the oral glucose tolerance test (OGTT). At the end of pregnancy, they were anesthetized and killed to collect blood and pancreas samples. The uterine horns were exposed for an evaluation of maternal reproductive outcomes and embryofetal development, and the offspring's liver samples were collected for redox status measurement. Nondiabetic and diabetic rats supplemented with Ca2+ showed no influence on glucose tolerance, redox status, insulin synthesis, serum calcium levels, and embryofetal losses. The reduced rate of newborns classified as adequate for gestational age (AGA) and higher rates of LGA (large) and small (LGA) newborns and higher -SH and GSH-Px antioxidant activities in female pups were observed in diabetic dams, regardless of supplementation. Thus, maternal supplementation caused no improvement in glucose tolerance, oxidative stress biomarkers, embryofetal growth and development, and antioxidants in pups from diabetic mothers.

Short-term Cafeteria Diet Is Associated with Fat Mass Accumulation, Systemic and Amygdala Inflammation, and Anxiety-like Behavior in Adult Male Wistar Rats.

Obesity is linked to metabolic, hormonal and biochemical alterations, and is also a risk factor for behavioral disorders. Evidence suggests that these disorders may be related to the consumption of hypercaloric diets, fat mass accumulation and changes in inflammation and redox status. Although much is known about the chronic effects of hypercaloric diets on mental health, few studies have evaluated the consequences of short-term exposure of these diets on behavior. The aim of this study was to evaluate nutritional, behavioral (anxiety-like), inflammatory and redox status parameters in adult male Wistar rats exposed to short-term cafeteria diet. Adult Wistar male rats (90 days-old; n = 12/group) received, during 14 days, the diets: Control- standard diet; Simple Cafeteria Diet (SCD)- homogeneous cafeteria diet. Varied Cafeteria Diet (VCD)- cafeteria diet with rotation and variation. Nutritional analyzes and tests for anxiety-like behaviors were performed, in addition to inflammatory and redox status measurements in blood and amygdala. The SCD group showed higher fat energy intake, while the VCD group consumed more energy from carbohydrates. SCD and VCD showed higher fat mass accumulation, in addition to higher levels of TNFα, INFγ, TBARS and FRAP in the blood. Also, SCD and VCD groups reported high levels of TNFα in the amygdala. Regarding behavioral evaluations, SCD and VCD groups showed anxiogenesis in the elevated plus maze, light-dark box, and open field tests. Therefore, the two cafeteria diets induced obesity and systemic inflammation, which in turn, resulted in an increase in amygdala TNFα levels and anxiety-like behaviors in Wistar rats.

Diets Supplemented with Probiotics Improve the Performance of Broilers Exposed to Heat Stress from 15 Days of Age.

The poultry sector demands alternative additives to antibiotics that can be used as performance enhancers. Therefore, this experiment was conducted to evaluate the probiotics effects on performance, intestinal health, and redox status of 720 broilers exposed to heat stress from 15 days of age. Eight dietary treatments were evaluated: basal diet (BD) without antibiotic and probiotic (T1); BD supplemented with antibiotic zinc bacitracin (T2), BD supplemented with commercial probiotic of Bacillus subtilis DSM 17,299 (T3), BD supplemented with non-commercial probiotic of Lactococcus lactis NCDO 2118, Lactobacillus delbrueckii CNRZ 327, Escherichia coli CEC15, or Saccharomyces boulardii (T4 to T7), and BD simultaneously supplemented with the four non-commercial probiotics (T8). Feed intake, weight gain, and feed conversion were determined in the period from 1 to 42 days of age. Carcass and cuts yield, abdominal fat deposition, cloacal temperature, weight and length of intestine, activity of myeloperoxidase and eosinophilic peroxidase enzymes in the jejunum, jejunal histomorphometry, relative gene expression in the jejunum (occludin, zonulin, interleukin-8, cholecystokinin, ghrelin, and heat shock protein-70), and liver (heat shock protein-70), in addition to malondialdehyde level and superoxide dismutase activity in the intestine, liver, and blood, were measured in broilers at 42 days old. As main results, broilers fed T1 diet exhibited lower weight gain (3.222 kg) and worse feed conversion (1.70 kg/kg). However, diets containing non-commercial probiotics resulted in up to 3.584 kg of weight gain and improved feed conversion by up to 10%, similar to that observed for broilers of the T2 and T3 groups.

Temporal analysis of paracetamol-induced hepatotoxicity.

Paracetamol-induced hepatotoxicity (APAP) causes severe damage that may be irreversible. Understanding the evolution of liver injury caused by overdose of the drug is important to assist in the treatment. In the present study, we evaluated the acute intoxication by APAP (500 mg/kg) in periods of 3 and 12 hours in C57BL/6 mice through biochemical, histological, inflammatory parameters, and the redox status. The results showed that in the 3-hour period there was an increase in creatinine dosage and lipid peroxidation (TBARS) compared to the control group. In the period of 12 hours after APAP intoxication all parameters evaluated were altered; there was an increase of ALT, AST, and necrosis, besides the increase of redox status biomarkers as carbonylated protein, TBARS, and MMP-9. We also observed activation of the inflammasome pathway as well as a reduction in the regenerative capacity of hepatocytes with a decrease in binucleated liver cells. In cytochrome gene expression, the mRNA level increased in CYP2E1 isoenzyme and reduced CYP1A2 expression. This study indicated that early treatment is necessary to mitigate APAP-induced acute liver injury, and alternative therapies capable of controlling the progression of intoxication in the liver are needed.

A Lower Serum Antioxidant Capacity as a Distinctive Feature for Women with HER2+ Breast Cancer: A Preliminary Study.

The overexpression of HER2 in breast cancer (BC) can contribute to redox imbalance, which is related to damage and structural modification in many biomolecules. To the best of our knowledge, this is the first study that has investigated the infrared spectrum wavenumbers obtained by ATR-FTIR and their relationship with the levels of redox status markers such as reduced glutathione, superoxide dismutase (SOD), catalase, Ferric Reducing Antioxidant Power (FRAP), and protein carbonyl among women with HER2+ BC, HER2- BC, and benign breast disease (BBD). The study was conducted with 25 women, 17 of whom were diagnosed with BC (6 HER2+ and 11 HER2-) and 8 with BBD. Our results indicate HER2+ BC cases could be distinguished from HER2- BC and BBD cases by their serum's antioxidant capacity [HER2+ BC vs. HER2- BC (AUC = 0.818; specificity = 81.82%; sensitivity = 66.67%); HER2+ BC vs. BBD (AUC = 0.875; specificity = 75%; sensitivity = 83.33%)]. The changes in biochemical terms that occur in serum as a result of the scarcity of antioxidants are related to a peculiar fingerprint in the infrared spectrum obtained by ATR-FTIR. In the serum of women with BBD, the SOD enzyme level is the highest, and this characteristic allowed us to distinguish them from HER2- BC. Finally, data regarding the serological antioxidant capacity of FRAP and the infrared spectrum by ATR-FTIR will allow us to assess biochemical changes that occur before clinical signs, indicating whether changes in therapy or interventions are necessary.

Medical ozone arrests oxidative damage progression and regulates vasoactive mediator levels in elderly patients (60-70 years) with oxidative etiology diseases.

Medical ozone reestablishes cellular redox balance so that it may be a valid therapeutic approach in the prevention and management of age-related diseases with oxidative etiology in older people. The aim of this study is to evaluate oxidative stress and some vasoactive substances in elderly (60-70 years) rheumatoid arthritis patients with diabetes and hypertension, as well as another group with bronchial asthma patients in order to demonstrate the beneficial effects of medical ozone in the prevention and therapy of age-related diseases in these age groups. A randomized clinical study with 45 older patients (60-70 years) was performed. Group I (n = 15) with rheumatoid arthritis + diabetes and hypertension received no ozone treatment, and group II (n = 30) was treated with medical ozone. This group was divided into two subgroups (n = 15 each), group IIa: the same as group I + medical ozone and group IIb: bronchial asthma patients. Indicators of RA in I and IIa groups were evaluated. Redox balance was assessed through defense and injury biomarkers. Thromboxane A2 (TXA2) and prostacyclin levels were assessed in group IIb patients. Medical ozone arrested oxidative injury progression in the Ia group and decreased thromboxane levels and the TXA2/6-keto PGF1α ratio in the IIb group. Medical ozone arrested the progression of oxidative damage and modulated those endogenous mechanisms that promote a suitable redox status and TXA2/PGI2 balance. These results suggest that medical ozone may become a standard approach in the prevention and management of age-related oxidative diseases in elderly people.

Piperine as Therapeutic Agent in Paracetamol-Induced Hepatotoxicity in Mice.

High doses of paracetamol (APAP) can cause irreversible liver damage. Piperine (P) inhibits cytochrome P450, which is involved in the metabolism of various xenobiotics, including paracetamol. We evaluated the hepatoprotective effects of piperine with or without N-acetylcysteine (NAC) in APAP-induced hepatotoxicity. The mice were treated with two doses of piperine (P20 or P40) and/or NAC at 2 h after administration of APAP. The NAC+P20 and NAC+P40 groups showed a reduced area of necrosis, MMP-9 activity, and Casp-1 expression. Furthermore, the NAC+P20 group was the only treatment that reduced alanine aminotransferase (ALT) and increased the levels of sulfhydryl groups (-SH). In the NAC+P40 group, NLRP-3 expression was reduced. Aspartate aminotransferase (AST), thiobarbituric acid-reactive substances (TBARS), and IL-1ß expression decreased in the NAC, NAC+P20, and NAC+P40 groups compared to the APAP group. The liver necrosis area, TNF levels, carbonylated protein, and IL-18 expression decreased in the P40, NAC, NAC+P20, and NAC+P40 groups compared to the APAP group. The cytokine IL-6 was reduced in all treatments. Piperine can be used in combination with NAC to treat APAP-induced hepatotoxicity.

Niveles glutatión reducido y estado redox celular en pacientes pediátricos con inmunodeficiencias / Reduced glutathione levels and cellular redox status in pediatric patients with immunodeficiencies

Introducción: Las alteraciones en el estado redox celular se han descrito como factores causales en diversas enfermedades. La depleción del glutatión reducido se ha asociado fundamentalmente a enfermedades neurodegenerativas, pulmonares, hepáticas, cardiovasculares e inmunológicas. Objetivo: Determinar las concentraciones de glutatión reducido y el estado redox celular en pacientes pediátricos con inmunodeficiencias. Métodos: Se estudiaron 21 pacientes con inmunodeficiencias procedentes de la consulta de Inmunogenética, en edades comprendidas entre 1 y 8 años, de ambos sexos, y 8 niños en el mismo rango de edad de los pacientes, como grupo control, con estudios de inmunidad humoral y celular normales. Los pacientes con diagnóstico de inmunodeficiencia se dividieron para su estudio en 2 grupos según el componente afectado de la respuesta inmune: humoral y celular. Fueron determinadas las concentraciones intraeritrocitarias de glutatión reducido y oxidado, mediante un método de HPLC-UV. Para evaluar el estado redox celular se calculó la relación entre las formas reducidas y oxidadas del glutatión (GSH/GSSG). Resultados: Las concentraciones de glutatión reducido y el estado redox celular se encontraron disminuidos en ambos grupos de pacientes en relación con los niños sin inmunodeficiencia (p=0,031 y p=0,03; respectivamente). El glutatión oxidado no mostró diferencias entre los grupos. Conclusiones: En los pacientes con inmunodeficiencia se evidenció la afectación del estado redox celular como consecuencia de la disminución del glutatión reducido. Este primer acercamiento ofreció las potencialidades del empleo de estos biomarcadores en la evaluación integral de pacientes con inmunodeficiencia(AU)

Introduction: Alterations in the cellular redox state have been described as causal factors in various diseases. Reduced glutathione depletion has been fundamentally associated with neurodegenerative, pulmonary, liver, cardiovascular and immunological diseases. Objective: To determine the concentrations of reduced glutathione and the cellular redox status in pediatric patients with immunodeficiencies. Methods: We studied 21 patients with immunodeficiencies from the immunogenetic service, aged between 1 and 8 years and as a control group, 8 children in the same age range as the patients, with normal humoral and cellular immunity studies. Patients diagnosed with immunodeficiency were divided into two groups according to the affected component of the immune response: humoral and cellular. The intraerythrocyte concentrations of oxidized and reduced glutathione were determined by means of an HPLC-UV method. To evaluate the cellular redox state, the relationship between the reduced and oxidized forms of glutathione (GSH/GSSG) was calculated. Results: Reduced glutathione concentrations and cellular redox status were found to be decreased in both groups of patients in relation to children without immunodeficiency (p=0,031 and p=0,03; respectively). Oxidized glutathione showed no difference between the groups. Conclusions: In patients with immunodeficiency, the cellular redox state is affected as a consequence of the decrease in reduced glutathione. This first approach offers the potential for the use of these biomarkers in the comprehensive evaluation of patients with immunodeficiency(AU)

Quinolinic Acid Impairs Redox Homeostasis, Bioenergetic, and Cell Signaling in Rat Striatum Slices: Prevention by Coenzyme Q10.

Quinolinic acid (QUIN) is an important agonist of NMDA receptors that are found at high levels in cases of brain injury and neuroinflammation. Therefore, it is necessary to investigate neuroprotection strategies capable of neutralizing the effects of the QUIN on the brain. Coenzyme Q10 (CoQ10) is a provitamin that has an important antioxidant and anti-inflammatory action. This work aims to evaluate the possible neuroprotective effect of CoQ10 against the toxicity caused by QUIN. Striatal slices from 30-day-old Wistar rats were preincubated with CoQ10 25-100 µM for 15 min; then, QUIN 100 µM was added to the incubation medium for 30 min. A dose-response curve was used to select the CoQ10 concentration to be used in the study. Results showed that QUIN caused changes in the production of ROS, nitrite levels, activities of antioxidant enzymes, glutathione content, and damage to proteins and lipids. CoQ10 was able to prevent the effects caused by QUIN, totally or partially, except for damage to proteins. QUIN also altered the activities of electron transport chain complexes and ATP levels, and CoQ10 prevented totally and partially these effects, respectively. CoQ10 prevented the increase in acetylcholinesterase activity, but not the decrease in the activity of Na+,K+-ATPase caused by QUIN. We also observed that QUIN caused changes in the total ERK and phospho-Akt content, and these effects were partially prevented by CoQ10. These findings suggest that CoQ10 may be a promising therapeutic alternative for neuroprotection against QUIN neurotoxicity.

Tannic Acid Attenuates Peripheral and Brain Changes in a Preclinical Rat Model of Glioblastoma by Modulating Oxidative Stress and Purinergic Signaling.

Glioblastoma (GB) is a highly aggressive and invasive brain tumor; its treatment remains palliative. Tannic acid (TA) is a polyphenol widely found in foods and possesses antitumor and neuroprotective activities. This study aimed to investigate the effect of TA on oxidative stress parameters and the activity of ectonucleotidases in the serum, platelets, and lymphocytes and/or in the brain of rats with preclinical GB. Rats with GB were treated intragastrically with TA (50 mg/kg/day) for 15 days or with a vehicle. In the platelets of the animals with glioma, the adenosine triphosphate (ATP) and adenosine monophosphate (AMP) hydrolysis and the catalase (CAT) activity decreased. Besides, the adenosine diphosphate (ADP) hydrolysis, adenosine (Ado) deamination, and the reactive oxygen species (ROS) and nitrite levels were increased in glioma animals; however, TA reversed ROS and nitrite levels and AMP hydrolysis alterations. In lymphocytes from animals with glioma, the ATP and ADP hydrolysis, as well as Ado deamination were increased; TA treatment countered this increase. In the brain of the animals with glioma, the ROS, nitrite, and thiobarbituric acid reactive substance (TBARS) levels increased and the thiol (SH) levels and CAT and superoxide dismutase (SOD) activities were decreased; TA treatment decreased the ROS and TBARS levels and restored the SOD activity. In the serum of the animals with glioma, the ATP hydrolysis decreased; TA treatment restored this parameter. Additionally, the ROS levels increased and the SH and SOD activity decreased by glioma implant; TA treatment enhanced nitrite levels and reversed SOD activity. Altogether, our results suggest that TA is an important target in the treatment of GB, as it modulates purinergic and redox systems.

The chloroplast redox-responsive transcriptome of solanaceous plants reveals significant nuclear gene regulatory motifs associated to stress acclimation.

KEY MESSAGE: Transcriptomes of solanaceous plants expressing a plastid-targeted antioxidant protein were analysed to identify chloroplast redox networks modulating the expression of nuclear genes associated with stress acclimation. Plastid functions depend on the coordinated expression of nuclear genes, many of them associated to developmental and stress response pathways. Plastid-generated signals mediate this coordination via retrograde signaling, which includes sensing of chloroplast redox state and levels of reactive oxygen species (ROS), although it remains a poorly understood process. Chloroplast redox poise and ROS build-up can be modified by recombinant expression of a plastid-targeted antioxidant protein, i.e., cyanobacterial flavodoxin, with the resulting plants displaying increased tolerance to multiple environmental challenges. Here we analysed the transcriptomes of these flavodoxin-expressing plants to study the coordinated transcriptional responses of the nucleus to the chloroplast redox status and ROS levels during normal growth and stress responses (drought or biotic stress) in tobacco and potato, members of the economically important Solanaceae family. We compared their transcriptomes against those from stressed and mutant plants accumulating ROS in different subcellular compartments and found distinct ROS-related imprints modulated by flavodoxin expression and/or stress. By introducing our datasets in a large-scale interaction network, we identified transcriptional factors related to ROS and stress responses potentially involved in flavodoxin-associated signaling. Finally, we discovered identical cis elements in the promoters of many genes that respond to flavodoxin in the same direction as in wild-type plants under stress, suggesting a priming effect of flavodoxin before stress manifestation. The results provide a genome-wide picture illustrating the relevance of chloroplast redox status on biotic and abiotic stress responses and suggest new cis and trans targets to generate stress-tolerant solanaceous crops.

A role of Na+, K+ -ATPase in spatial memory deficits and inflammatory/oxidative stress after recurrent concussion in adolescent rats.

Sports-related concussions are particularly common during adolescence, and there is insufficient knowledge about how recurrent concussions in this phase of life alter the metabolism of essential structures for memory in adulthood. In this sense, our experimental data revealed that seven recurrent concussions (RC) in 35-day-old rats decreased short-term and long-term memory in the object recognition test (ORT) 30 days after injury. The RC protocol did not alter motor and anxious behavior and the immunoreactivity of brain-derived neurotrophic factor (BDNF) in the cerebral cortex. Recurrent concussions induced the inflammatory/oxidative stress characterized here by increased glial fibrillary acidic protein (GFAP), interleukin 1ß (IL 1ß), 4-hydroxynonenal (4 HNE), protein carbonyl immunoreactivity, and 2',7'-dichlorofluorescein diacetate oxidation (DCFH) levels and lower total antioxidant capacity (TAC). Inhibited Na+,K+-ATPase activity (specifically isoform α2/3) followed by Km (Michaelis-Menten constant) for increased ATP levels and decreased immunodetection of alpha subunit of this enzyme, suggesting that cognitive impairment after RC is caused by the inability of surviving neurons to maintain ionic gradients in selected targets to inflammatory/oxidative damage, such as Na,K-ATPase activity.

Systemic antioxidant and anti-inflammatory effects of yellow passion fruit bagasse extract during prostate cancer progression.

We evaluated the impact of yellow passion fruit (Passiflora edulis sp.) bagasse extract (PFBE) administration in systemic oxidative and inflammatory parameters in vivo, considering prostate cancer progression in transgenic mice (TRAMP). Piceatannol, scirpusin-B, dicaffeoylquinic acid, citric acid, and (+)-catechin were identified in PFBE, and the extract showed high in vitro antioxidant capacity. Some alterations in systemic parameters were verified during prostate cancer progression, as the increase in ALT and MDA levels, and SOD and GPx activities in the plasma. In the liver, higher MDA, TNF-α, and NF-κB levels, and GR and GPx activities were verified. Compared to their respective controls, the short- and long-term PFBE administration reduced MDA levels in the liver and plasma. The long-term treatment increased the catalase activity in the plasma, while the short-term treatment increased the hepatic SOD and catalase activities. Still, a reduction in hepatic TNF-α and NF-κB levels was verified after long-term treatment. PRACTICAL APPLICATIONS: Prostate cancer progression is associated with changes in systemic redox status and inflammation markers. Moreover, the intake of polyphenols with antioxidant properties, besides delaying prostate carcinogenesis, may improve the systemic antioxidant defenses and inflammatory response. In vitro studies pointed to a promising antioxidant and anti-inflammatory potential of yellow passion fruit bagasse. However, in vivo studies are scarce. Our results provided information about in vivo impacts of PFBE oral consumption on antioxidant defense and inflammation, indicating its potential as an adjuvant during the initial steps of prostate cancer.

Maternal exercise during pregnancy modulates mitochondrial function and redox status in a sex-dependent way in adult offspring's skeletal muscle.

Maternal exercise has shown beneficial effects on mother and child. Literature confirm progeny's cognition improvement, and upregulation in neurotrophins, antioxidant network, and DNA repair system. Considering that there is a lack of information demonstrating the impact of maternal exercise on offspring's skeletal muscle, we aimed to investigate the mitochondrial and redox effects elicited by maternal swimming. Adult female Wistar rats were divided into three groups: control sedentary, free swimming, and swimming with overload (2% of the body weight). Exercised groups were submitted weekly to five swimming sessions (30 min/day), starting 1 week prior to the mating and lasting to the delivery. Gastrocnemius and soleus muscle from 60-day-old offspring were analyzed. Our results clearly showed a sex-dependent effect. Male soleus showed increased mitochondrial functionality in the overload group. Female muscle from the overload group adapted deeply. Considering the redox status, the female offspring delivered to overload exercised dams presented reduced oxidants levels and protein damage, allied to downregulated antioxidant defenses. We also observed an increase in the mitochondrial function in the gastrocnemius muscle of the female offspring born from overload exercised dams. Soleus from female delivered to the overload exercise group presented reduced mitochondrial activity, as well as reduced reactive species, protein carbonyls, and antioxidant network, when compared to the male. In conclusion, maternal exercise altered the redox status and mitochondrial function in the offspring's skeletal muscle in a sex-dependent way. The clinical implication was not investigated; however, the sexual dimorphism in response to maternal exercise might impact exercise resilience in adulthood.

Storage Duration Affects the Quantification of Oxidative Stress Markers in the Gastrocnemius, Heart, and Brain of Mice Submitted to a Maximum Exercise.

This study investigated the effect of sample storage duration on the quantification of oxidative stress markers in the gastrocnemius, heart, and brain of mice submitted to a maximum swimming exercise. Thiobarbituric acid reactive substances (TBARSs), protein carbonyl derivatives, total antioxidant capacity (TAC), and the activity of superoxide dismutase (SOD) and catalase (CAT) were quantified in fresh tissues and in samples stored at -80°C for 1, 3, or 6 months, from exercised (n = 13) and nonexercised mice (n = 13). Except for protein carbonyl derivatives in the heart, the exercise resulted in the modification of all markers in all fresh-evaluated samples (p < 0.001). The storage duration did not modify the effect of exercise on protein carbonyl derivatives and TAC. TBARS was stable for 3 months in the gastrocnemius and for 1 month in frozen heart and brain. Accordingly, the exercise effect on TBARS levels observed in fresh samples was absent in the gastrocnemius frozen for 6 months (p = 0.98) and in the heart and brain frozen for 3 months (p = 0.07 and 0.28, respectively) or more (p = 0.21 for heart and p > 0.99 for brain). In addition, CAT and SOD activities were reduced by storage duration in all tissues evaluated (p < 0.05). Our findings show that sample storage duration alters the quantification of oxidative stress markers in mice submitted to maximum exercise, and its effect is tissue and marker dependent. Some recommendations to achieve more accurate and reproducible data in the exercise physiology and oxidative stress markers field are presented.