Diazoxide and moderate-intensity exercise improve skeletal muscle function by decreasing oxidants and enhancing antioxidant defenses in hypertensive male rats.

High sodium intake is decisive in the incidence increase and prevalence of hypertension, which has an impact on skeletal muscle functionality. Diazoxide is an antihypertensive agent that inhibits insulin secretion and is an opener of KATP channels (adosine triphosphate sensitive potasium channels). For this reason, it is hypothesized that moderate-intensity exercise and diazoxide improve skeletal muscle function by reducing the oxidants in hypertensive rats. Male Wistar rats were assigned into eight groups: control (CTRL), diazoxide (DZX), exercise (EX), exercise + diazoxide (EX + DZX), hypertension (HTN), hypertension + diazoxide (HTN + DZX), hypertension + exercise (HTN + EX), and hypertension + exercise + diazoxide (HTN + EX + DZX). To induce hypertension, the rats received 8% NaCl dissolved in water orally for 30 days; in the following 8 weeks, 4% NaCl was supplied to maintain the pathology. The treatment with physical exercise of moderate intensity lasted 8 weeks. The administration dose of diazoxide was 35 mg/kg intraperitoneally for 14 days. Tension recording was performed on the extensor digitorum longus and the soleus muscle. Muscle homogenates were used to measure oxidants using fluorescent probe and the activity of antioxidant systems. Diazoxide and moderate-intensity exercise reduced oxidants and increased antioxidant defenses.

Relationship between inflammation and oxidative stress and its effect on multiple sclerosis.

INTRODUCTION: This paper highlights the relationship of inflammation and oxidative stress as damage mechanisms of Multiple Sclerosis (MS), considered an inflammatory and autoimmune disease. DEVELOPMENT: The oxidative stress concept has been defined by an imbalance between oxidants and antioxidants in favor of the oxidants. There is necessary to do physiological functions, like the respiration chain, but in certain conditions, the production of reactive species overpassed the antioxidant systems, which could cause tissue damage. On the other hand, it is well established that inflammation is a complex reaction in the vascularized connective tissue in response to diverse stimuli. However, an unregulated prolonged inflammatory process also can induce tissue damage. CONCLUSION: Both inflammation and oxidative stress are interrelated since one could promote the other, leading to a toxic feedback system, which contributes to the inflammatory and demyelination process in MS.

Preventive effects of systemic Pistacia eurycarpa Yalt. administration on alveolar bone loss and oxidative stress in rats with experimental periodontitis.

OBJECTIVE: This study aimed to investigate the effects of systemic administration of P. eurycarpa Yalt. plant extract on alveolar bone loss and oxidative stress biomarkers in gingival tissue in a rat model of experimental periodontitis. METHODOLOGY: 32 male Wistar albino rats, weighing 200-250 g, were divided into four groups (n=8): Healthy control (HC), Experimental periodontitis control (EPC), Experimental periodontitis 400 mg/kg (EP400), Experimental periodontitis 800 mg/kg (EP800). Experimental periodontitis was induced using the ligating method. Distilled water was administered to the HC and EPC groups and the plant extract was administered to the EP400 and EP800 groups by oral gavage at doses of 400 mg/kg and 800 mg/kg, respectively. The rats were sacrificed on the 15th day. The values of glutathione peroxidase GSH-Px, malondialdehyde (MDA), superoxide dismustase (SOD), interleukin-1ß (IL-1ß), interleukin-10 (IL-10), total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI) in the gingival tissues were analyzed by ELISA tests. Alveolar bone loss was assessed using micro-CT images of the maxilla. RESULTS: Although the IL-1ß, TOS, OSI results of the healthy control group were lower than those of the other groups, the TAS values were higher (p<0.05). No significant difference was found in the biochemical parameters among the EPC, EP400, and EP800 groups (p>0.05). Alveolar bone loss was significantly reduced in the extract groups compared to the EPC group (p<0.001). CONCLUSION: Within the limitations of this study, it was observed that the systemic P. eurycarpa extract application reduced alveolar bone loss in a rat model of experimental periodontitis. Further studies are needed to elucidate the beneficial effects of P. eurycarpa.

Anammox with alternative electron acceptors: perspectives for nitrogen removal from wastewaters.

In the context of the anaerobic ammonium oxidation process (anammox), great scientific advances have been made over the past two decades, making anammox a consolidated technology widely used worldwide for nitrogen removal from wastewaters. This review provides a detailed and comprehensive description of the anammox process, the microorganisms involved and their metabolism. In addition, recent research on the application of the anammox process with alternative electron acceptors is described, highlighting the biochemical reactions involved, its advantages and potential applications for specific wastewaters. An updated description is also given of studies reporting the ability of microorganisms to couple the anammox process to extracellular electron transfer to insoluble electron acceptors; particularly iron, carbon-based materials and electrodes in bioelectrochemical systems (BES). The latter, also referred to as anodic anammox, is a promising strategy to combine the ammonium removal from wastewater with bioelectricity production, which is discussed here in terms of its efficiency, economic feasibility, and energetic aspects. Therefore, the information provided in this review is relevant for future applications.

Superoxide, nitric oxide and peroxynitrite production by macrophages under different physiological oxygen tensions.

Macrophages count on two O2-consuming enzymes to form reactive radical species: NAPDH oxidase 2 (Nox2) and nitric oxide synthase 2 (inducible isoform, iNOS) that produce superoxide radical (O2•-) and nitric oxide (•NO), respectively. If formed simultaneously, the diffusion-controlled reaction of O2•- and •NO yields peroxynitrite, a potent cytotoxic oxidant. In human tissues and cells, the oxygen partial pressure (pO2) normally ranges within 2-14 %, with a typical average pO2 value for most tissues ca. 5 %. Given that O2 is a substrate for both Nox2 and iNOS, its tissue and cellular concentration can affect O2•- and •NO production. Also, O2 is a modulator of the macrophage adaptative response and may influence iNOS expression in a hypoxia inducible factor 1-α (HIF1α-)-dependent manner. However, most of the reported experiments in cellula, analyzing the formation and effects of O2•- and •NO during macrophage activation and cytotoxicity towards pathogens, have been performed in cells exposed to atmospheric air supplemented with 5 % CO2; under these conditions, most cells are exposed to supraphysiologic oxygen tensions (ca. 20 % O2) which are far from the physiological pO2. Here, the role of O2 as substrate in the oxidative response of J774A.1 macrophages was explored upon exposure to different pO2 and O2•- and •NO formation rates were measured, obtaining a KM of 26 and 42 µM O2 for Nox2 and iNOS, respectively. Consequently, peroxynitrite formation was influenced by pO2, reaching a maximum at ≥ 10 % O2, but even at levels as low as 2 % O2, a substantial formation rate of this oxidant was detected. Indeed, the cytotoxic capacity of immunostimulated macrophages against the intracellular parasite T. cruzi was significant, even at low pO2 values, confirming the role of peroxynitrite as a potent oxidizing cytotoxin within a wide range of physiological oxygen tensions.

Assessment of the toxic effects of levetiracetam on biochemical, functional, and redox parameters of salivary glands in male Wistar rats.

Levetiracetam (LEV) is an anticonvulsant for epilepsy. The toxic effects of this medication in tissues have been associated with redox state imbalance, which can lead to salivary gland dysfunction. Therefore, the current work investigated the effects of LEV on the biochemical, functional, and redox parameters of the parotid and submandibular glands in rats. For this, male Wistar rats (Rattus norvegicus albinus) were randomly divided into 3 groups (n = 10/group): Control (0.9% saline solution), LEV100 (100 mg/kg), and LEV300 (300 mg/kg). After 21 consecutive days of intragastric gavage treatments, pilocarpine stimulated saliva secretion was collected for salivary biochemical analysis. The extracted salivary glands were utilized for histomorphometry and redox state analyses. Our results showed that LEV300 increased plasma hepatotoxicity markers and reduced salivary amylase activity and the acinar surface area of the parotid gland. Total oxidant capacity and oxidative damage to lipids and proteins were higher in the parotid gland, while total antioxidant capacity and uric acid levels were reduced in the submandibular gland of the LEV100 group compared to Control. On the other hand, total oxidant capacity, oxidative damage to lipids and proteins, total antioxidant capacity, and uric acid levels were lower in both salivary glands of the LEV300 group compared to Control. Superoxide dismutase and glutathione peroxidase activities were lower in the salivary glands of treated animals compared to Control. In conclusion our data suggest that treatment with LEV represents a potentially toxic agent, that contributes to drug-induced salivary gland dysfunction.

Novel Probucol Analogue, 4,4'-Diselanediylbis (2,6-Di-tert-Butylphenol), Prevents Oxidative Glutamate Neurotoxicity In Vitro and Confers Neuroprotection in a Rodent Model of Ischemic Stroke.

Oxidative glutamate toxicity is regarded as one of the injurious mechanisms associated with ischemic stroke, which represents a major health problem and requires improved pharmacological treatments. We designed and synthesized two new probucol analogues [2,6-di-tert-butyl-4-selenocyanatophenol (C1) and 4,4'-diselanediylbis (2,6-di-tert-butylphenol) (C2)] and investigated their effects against glutamate-induced neuronal oxidative toxicity in vitro in cultured HT22 cells, compared with their parental compound (probucol). In addition, C2, which exhibited the lowest toxicity, was investigated in an in vivo rodent model of ischemic stroke. Glutamate caused concentration- and time-dependent cytotoxicity in HT22 neuronal cells, which was preceded by increased levels of oxidants and depletion of the antioxidant glutathione. The analogues (C1 and C2), but not probucol, significantly decreased the levels of oxidants (including mitochondrial superoxide anion and lipid reactive oxygen species (ROS)) and protected against glutamate-induced cytotoxicity. In the in vivo model of ischemic stroke, which was based on central injections of the vasoconstrictor agent endothelin-1 (800 pmol/site), C2 (20 or 50 mg/kg/day, intraperitoneally, for 4 consecutive days after stroke) displayed significant beneficial effects against ischemic injury in vivo, improving rats' motor-related behavioral skills and decreasing stroke-related striatal gliosis. This is the first study to design, synthesize, and present a probucol analogue (C2) with in vivo beneficial effects against ischemic stroke. This novel compound, which was able to mitigate glutamate-induced oxidative toxicity in vitro, represents a promising neuroprotective drug.

The ferryl generation by fenton reaction driven by catechol.

The Fenton and Fenton-like reactions are based on the decomposition of hydrogen peroxide catalyzed by Fe(II), primarily producing highly oxidizing hydroxyl radicals (HO∙). While HO∙ is the main oxidizing species in these reactions, Fe(IV) (FeO2+) generation has been reported as one of the primary oxidants. FeO2+ has a longer lifetime than HO∙ and can remove two electrons from a substrate, making it a critical oxidant that may be more efficient than HO∙. It is widely accepted that the preferential generation of HO∙ or FeO2+ in the Fenton reaction depends on factors such as pH and Fe: H2O2 ratio. Reaction mechanisms have been proposed to generate FeO2+, which mainly depend on the radicals generated in the coordination sphere and the HO∙ radicals that diffuse out of the coordination sphere and react with Fe(III). As a result, some mechanisms are dependent on prior HO∙ radical production. Catechol-type ligands can induce and amplify the Fenton reaction by increasing the generation of oxidizing species. Previous studies have focused on the generation of HO∙ radicals in these systems, whereas this study investigates the generation of FeO2+ (using xylidine as a selective substrate). The findings revealed that FeO2+ production is increased compared to the classical Fenton reaction and that FeO2+ generation is mainly due to the reactivity of Fe(III) with HO∙ from outside the coordination sphere. It is proposed that the inhibition of FeO2+ generation via HO∙ generated from inside the coordination sphere is caused by the preferential reaction of HO∙ with semiquinone in the coordination sphere, favoring the formation of quinone and Fe(III) and inhibiting the generation of FeO2+ through this pathway.

miR-21, miR-221, and miR-222 upregulation in lung cancer promotes metastasis by reducing oxidative stress and apoptosis.

OBJECTIVE: The purpose of our research was to observe the effects of miR-21, miR-221, and miR-222, as well as their target genes on oxidative stress, lung cancer formation, and metastasis. METHODS: Positron emission tomography/computed tomography, fiberoptic bronchoscopy, and/or endobronchial ultrasonography were performed on a total of 69 lung cancer patients to detect the presence or absence of metastasis, and the patients were classified based on the types of cancer. Total RNA and miRNA were isolated from the obtained biopsy samples. The quantitative analysis of hsa-miR-21-5p, hsa-miR-222-3p, and hsa-miR-221-3p and their target genes was performed by the RT-qPCR method. In determining oxidative stress, total antioxidant status and total oxidant status in tissue and total thiol and native thiol in blood were determined spectrophotometrically. OSI and disulfide were calculated. RESULTS: We discovered that the metastasis group had higher levels of hsa-miR-21-5p, hsa-miR-221-3p, and hsa-miR-222-3p (p<0.05). While TIMP3, PTEN, and apoptotic genes decreased in metastasis, anti-apoptotic genes increased (p<0.05). In addition, while oxidative stress decreased in the metastasis group, no change was found in the serum (p>0.05). CONCLUSION: Our findings show that upregulation of hsa-miR-21-5p, hsa-miR-221-3p, and hsa-miR-222-3p effectively contributes to both proliferation and invasion by influencing oxidative stress and mitochondrial apoptosis.

Interactions Between Calcium Hypochlorite and Irrigants Commonly Used in Endodontic Practice: A Chemical Analysis.

INTRODUCTION: This study aimed to identify possible products resulting from chemical interactions between calcium hypochlorite (Ca[OCl]2) and other irrigants for endodontic use using electrospray ionization quadrupole time-of-flight mass spectrometry. METHODS: The 5.25% Ca(OCl)2 was associated with either 70% ethanol solution, distilled water, saline solution (0.9% sodium chloride), 5% sodium thiosulfate, 10% citric acid, 17% ethylenediaminetetraacetic acid (EDTA), or 2% chlorhexidine (CHX). The reaction ratio was 1:1 and the products obtained were analyzed by electrospray ionization quadrupole time-of-flight mass spectrometry. RESULTS: The interactions between Ca(OCl)2 and CHX generated an orange-brown precipitate, without identification of para-chloroaniline and between Ca(OCl)2 and sodium thiosulfate, a milky-white precipitate. Furthermore, when the oxidizing agent was associated with EDTA and citric acid, chlorine gas was released. As for the other associations, 70% ethanol, distilled water, and saline solution, no precipitation or gas release occurred. CONCLUSIONS: The orange-brown precipitate occurs due to the chlorination of guanidine nitrogens, and the milky-white precipitate is due to the partial neutralization of the oxidizing agent. The release of chlorine gas occurs due to the low pH of the mixture, which results in the rapid formation and decomposition of chlorine. In this context, an intermediate rinsed with distilled water, saline solution, and ethanol between Ca(OCl)2 and CHX, citric acid, and EDTA seems to be appropriate to prevent the formation of by-products when these irrigants need to be used in the canal. Furthermore, if it is necessary to use sodium thiosulfate, a larger volume of the solution must be used compared to that used for the oxidizing solution.

Characterization of the Trr/Trx system in the fungal pathogen Candida glabrata.

C. glabrata, an opportunistic fungal pathogen, can adapt and resist to different stress conditions. It is highly resistant to oxidant stress compared to other Candida spp and to the phylogenetically related but non-pathogen Saccharomyces cerevisiae. In this work, we describe the Trx/Trr system of C. glabrata composed of Trr1 and Trr2 (thioredoxin reductases) and Trx2 (thioredoxin) that are localized in the cytoplasm and Trx3 present in the mitochondrion. The transcriptional induction of TRR2 and TRX2 by oxidants depends on Yap1 and Skn7 and TRR1 and TRX3 have a low expression level. Both TRR2 and TRX2 play an important role in the oxidative stress response. The absence of TRX2 causes auxotrophy of methionine and cysteine. Trr1 and Trr2 are necessary for survival at high temperatures and for the chronological life span of C. glabrata. Furthermore, the Trx/Trr system is needed for survival in the presence of neutrophils. The role of TRR1 and TRX3 is not clear, but in the presence of neutrophils, they have non-overlapping functions with their TRR2 and TRX2 paralogues.

Simultaneous hydrodynamic cavitation and glow plasma discharge for the degradation of metronidazole in drinking water.

In this study, a novel hydrodynamic cavitation unit combined with a glow plasma discharge system (HC-GPD) was proposed for the degradation of pharmaceutical compounds in drinking water. Metronidazole (MNZ), a commonly used broad-spectrum antibiotic, was selected to demonstrate the potential of the proposed system. Cavitation bubbles generated by hydrodynamic cavitation (HC) can provide a pathway for charge conduction during glow plasma discharge (GPD). The synergistic effect between HC and GPD promotes the production of hydroxyl radicals, emission of UV light, and shock waves for MNZ degradation. Sonochemical dosimetry provided information on the enhanced formation of hydroxyl radicals during glow plasma discharge compared to hydrodynamic cavitation alone. Experimental results showed a MNZ degradation of 14% in 15 min for the HC alone (solution initially containing 300 × 10-6 mol L-1 MNZ). In experiments with the HC-GPD system, MNZ degradation of 90% in 15 min was detected. No significant differences were observed in MNZ degradation in acidic and alkaline solutions. MNZ degradation was also studied in the presence of inorganic anions. Experimental results showed that the system is suitable for the treatment of solutions with conductivity up to 1500 × 10-6 S cm-1. The results of sonochemical dosimetry showed the formation of oxidant species of 0.15 × 10-3 mol H2O2 L-1 in the HC system after 15 min. For the HC-GPD system, the concentration of oxidant species after 15 min reached 13 × 10-3 molH2O2L-1. Based on these results, the potential of combining HC and GPD systems for water treatment was demonstrated. The present work provided useful information on the synergistic effect between hydrodynamic cavitation and glow plasma discharge and their application for the degradation of antibiotics in drinking water.

Associations of adiposity and adipokine concentrations with anti- and oxidative markers in Brazilian children.

OBJECTIVE: The aim of this study was to evaluate the association of body fat, anti- and inflammatory adipokines with anti- and oxidative markers. METHODS: We conducted a cross-sectional study with 378 schoolchildren ages 8 to 9 y in Viçosa, Minas Gerais, Brazil. We obtained information on sociodemographic and lifestyle characteristics via questionnaires, measured height and weight, and estimated body fat by dual energy x-ray absorptiometry. Blood sample was collected to analyze the adipokines (adiponectin, leptin, chemerin, and retinol-binding protein 4) by enzyme-linked immunosorbent assay based on the sandwich principle; and anti- and oxidant markers (plasma ferric reducing antioxidant power [FRAP], superoxide dismutase [SOD], and malondialdehyde [MDA]) by enzymatic methods. Concentrations of anti- and oxidant markers were compared by percent body fat quartiles and adipokine concentrations terciles using of linear regression adjusted for potential confounders. RESULTS: Total and central body fat were positively associated with FRAP. Every 1 standard deviation (SD) of total fat was associated with 4.8 higher FRAP (95% confidence interval [CI], 2.7-7). Additionally, every 1 SD of truncal, android, and gynoid fat were associated with, respectively, 5, 4.6, and 4.6 higher FRAP (95% CI, 2.9-7.1; 2.6-6.7; and 2.4-6.8, respectively). However, adiponectin was inversely associated with FRAP; every adiponectin SD was related to -2.2 lower FRAP (95% CI, -3.9 to -0.5). Chemerin was positively associated with SOD [5.4 (95% CI, 1.9-8.8) SOD units per chemerin SD]. CONCLUSIONS: The body fat measures and adiposity-related inflammation (chemerin) were positively associated with antioxidative markers in children, whereas the adiponectin (anti-inflammatory marker) was inversely associated with FRAP (antioxidative marker).

The role of NMDA glutamate receptors in lung injury caused by chronic long-term intermittent hypobaric hypoxia.

Chronic intermittent hypoxia (CIH), a component of sleep apnea-hypopnea syndrome, is suggested to cause damage to lung tissue, and the role of glutamate is not well studied. We used a chronic long-term intermittent hypobaric hypoxia (CLTIHH) model of rats to find out if such procedure causes lung injury and the potential effect of N-methyl-D-aspartate receptors (NMDARs) by using receptor antagonist MK-801 (dizocilpine). Thirty-two rats were placed into four groups; a control and three CLTIHH groups where rats were placed into a low-pressure chamber set to 430 mmHg for 5 h/day, 5 days/week, for 5 weeks. Only one group received MK-801 (0.3 mg/kg, ip) daily. We evaluated tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-10, and nuclear factor (NF)-kB for the inflammatory process, superoxide dismutase (SOD), malondialdehyde (MDA), catalase (CAT), glutathione peroxidase (GPX), total antioxidant status (TAS), and total oxidant status (TOS) for oxidative stress, and caspase-9 levels. Blood plasma, bronchoalveolar fluid (BALF), and lung tissue extracts were evaluated. Both oxidant and inflammatory parameters were significantly increased in all the mediums of the CLTIHH groups except the group that received MK-801. Significant evidence was collected on MK-801 alleviating the effect of CLTIHH. Histological evaluations revealed lung damage and fibrotic changes in the CLTIHH groups. It was first shown that the CLTIHH procedure caused chronic lung injury, and that inflammation and oxidant stress were influential in the formation of lung injury. Secondly, NMDAR antagonist MK-801 effectively inhibited the development of lung injury and fibrosis.

Oxidation State in Peritoneal Dialysis in Patients with Type 2 Diabetes Mellitus.

End-stage renal disease (ESRD) progression is closely related to oxidative stress (OS). The study objective was to determine the oxidant and antioxidant status in peritoneal dialysis (PD) patients with type 2 diabetes mellitus (DM). An analytical cross-sectional study from the PD program was carried out with 62 patients, 22 with and 40 without DM. Lipoperoxides (LPO) levels in patients with DM, 3.74 ± 1.09 mM/L, and without DM, 3.87 ± 0.84 mM/L were found to increase compared to healthy controls (HC) 3.05 ± 0.58 mM/L (p = 0.006). The levels of the oxidative DNA damage marker (8-OH-dG) were found to be significantly increased in patients with DM, 1.71 ng/mL (0.19-71.92) and without DM, 1.05 ng/mL (0.16-68.80) front to 0.15 ng/mL (0.15-0.1624) of HC (p = 0.001). The antioxidant enzyme superoxide dismutase (SOD) activity was found to be significantly increased in patients with DM, 0.37 ± 0.15 U/mL, and without DM, 0.37 ± 0.17 compared to HC, 0.23 ± 0.05 U/mL (p = 0.038). The activity of the enzyme glutathione peroxidase (GPx) showed a significant increase (p < 0.001) in patients with DM, 3.56 ± 2.18 nmol/min/mL, and without DM, 3.28 ± 1.46 nmol/min/mL, contrary to the activity obtained in HC, 1.55 ± 0.34 nmol/min/mL. In conclusion, we found an imbalance of oxidative status in patients undergoing PD with and without DM through the significant increase in LPO oxidants and the marker of oxidative damage in DNA. The activity of the antioxidant enzymes SOD and GPx were significantly increased in patients with and without DM undergoing PD, possibly in an attempt to compensate for the deregulation of oxidants. Antioxidant enzymes could be promising therapeutic strategies as a complement to the management of chronic kidney diseases.

Lactation attenuates pro-oxidant reactions in the maternal brain.

Reactive oxygen species (ROS) are intimately linked to bioenergetics and redox biology, contributing to cellular functioning and physiological signaling, but also acting as toxic agents during oxidative stress. Hence, the balance between pro-oxidant reactions and the activity of antioxidant defenses sustains a basal oxidative status, controls the increase of redox signaling, and mediates potential pathological events during oxidative stress. Maternal experience, especially during nursing, requires high energetic demands and expenditure to ensure the well-being of the offspring. The mother must adapt from satisfying her own needs to additionally fulfilling those of her descendants. Oxidative stress has been proposed as one of the reproductive trade-off hallmarks. However, the oxidative shielding hypothesis has also been proposed in the context of reproduction. The reproductive experience induces a wide range of well-documented changes in the female brain, which potentially lead to protection against the enhanced oxidative activity. To date, the metabolic and cellular mechanisms that underlie lactation-induced neuroprotection against oxidants are unknown. The neuroendocrine changes in the brain of the lactating dam promote diminished propensity to excitotoxic brain injury and stress, as well as enhanced neuroprotection and plasticity. In addition to review studies on the oxidant balance due to motherhood, we included new data from our laboratory, addressing the importance of measuring pro-oxidant reactions in separated brain regions. The hippocampus of lactating rats exhibits lower levels of pro-oxidant reactions than that of virgin rats, supporting the oxidative shielding hypothesis in lactation.

Effects of substance use disorder on oxidative and antioxidative stress markers: A systematic review and meta-analysis.

Recently, it has been suggested that central and peripheral toxicities identified in persons with substance use disorder (SUD) could be partially associated with an imbalance in reactive oxygen species and antioxidant defenses. We conducted a systematic review and meta-analysis to investigate whether SUD is associated with oxidative stress and to identify biomarkers possibly more affected by this condition. We have included studies that analysed oxidant and antioxidant markers in individuals with SUD caused by stimulants, alcohol, nicotine, opioids, and others (cannabis, inhalants, and polysubstance use). Our analysis showed that persons with SUD show higher oxidant markers and lower antioxidant markers than healthy controls. SUD was associated specifically with higher levels of oxidant markers malondialdehyde, thiobarbituric acid reactive substances and lipid peroxidation. Conversely, the antioxidant superoxide dismutase and the total antioxidant capacity/status were lowered in the SUD group. A meta-regression analysis revealed that persons with alcohol use disorder had higher oxidative stress estimates than those with stimulant use disorder. Moreover, individuals evaluated during abstinence showed smaller antioxidant effect sizes than non-abstinent ones. Our findings suggest a clear oxidative imbalance in persons with SUD, which could lead to cell damage and result in multiple associated comorbidities, particularly accelerated aging.

Impacto do metilfenidato no estresse oxidativo e na plasticidade cerebral / Methylphenidate impact on oxidative stress and brain plasticity

Esse estudo avaliou o impacto do tratamento com cloridrato de metilfenidato (MFD) em crianças com Transtorno de Déficit de Atenção e Hiperatividade. O estudo incluiu metodologia variada, contendo estudo de revisão sobre efeito de metilfenidato sobre BDNF e estudo de coorte experimental. O estudo de revisão seguiu as diretrizes do PRISMA e foi registrado no PROSPERO. No estudo experimental, coorte aberta de centro único foi desenhada, com amostra de conveniência recrutada entre os anos de 2020 e 2022, no ambulatório de ensino da faculdade de Medicina da Universidade Federal de Viçosa (MG). Amostra de 62 crianças, 6 a 14 anos incompletos, sem tratamento prévio, diagnosticadas por psiquiatra infantil segundo os critérios do Manual Diagnóstico e Estatístico dos Transtornos Mentais (DSM5). Média de 8 consultas de acompanhamento clínico realizadas, com coletas de amostras biológicas em 3 delas: antes do início do MFD, com 12 e 24 semanas após uso da medicação. Amostra caracterizada quanto a dados sociodemográficos, sintomas de TDAH, avaliações clínica e psiquiátrica e testagem de inteligência pela psicologia. Amostras biológicas para dosagens séricas de marcadores oxidativos (níveis de capacidade antioxidante total -FRAP -, atividade de superóxido dismutase ­ SOD-, catalase ­ CAT -, glutathione -S-transferase -GST-, níveis de peroxidação lipídica e de proteínas carboniladas) foram coletadas de cada criança nos três momentos da avaliação. Metilfenidato de liberação imediata foi administrado na dosagem de média de 0,65mg/kg/dia. Usou-se o teste de Shapiro-Wilk e Kolmogorov-Smirnov para análise de normalidade. Frequências absolutas e relativas foram determinadas para as variáveis numéricas que foram descritas por suas médias e desvios padrões. Para comparações múltiplas dos parâmetros oxidativos foi realizado pós teste paramétrico de Tukey e para as demais variáveis análise de variância ANOVA (f). Análises dos parâmetros oxidativos foram realizadas no programa GraphPad Prism 7.0 (GraphPad Software, Inc. San Diego, CA, USA) e dos dados sociodemográficos e clínicos no software SPSS (versão 23.0 para Windows). Significância estatística foi considerada com p <0.05. Os resultados mostram: Sexo masculino predominante (71%), idade média 8,58 ± 1,91, predominância de apenas um cuidador - mãe e/ou pai biológico como chefe de família e maior frequência de tipo combinado de TDAH. Pressão arterial sistólica, frequência cardíaca e temperatura corporal alterações significativas, porém sem significância clínica. Índice massa corporal com diferença estatística, 37%, 19,3% e 21% das crianças apresentaram IMC acima do esperado para idade na avaliação 1, 2 e 3 respectivamente. Adesão ao tratamento medicamentoso permaneceu acima de 93,5% na 24ª semana. Durante o tratamento: FRAP não se alterou; atividade de SOD reduziu na 12ª semana em comparação à linha de base; atividade de CAT aumento significativo à 24ª em comparação 12ª semana; aumento significativo dos níveis de peroxidação lipídica à 24ª semana em comparação à 12ª semana. Aumento significativo das proteínas carboniladas na linha de base em comparação aos níveis da 12ª e 24ª semanas. O metilfenidato parece influenciar os parâmetros redox de crianças com TDAH, aumentando o estresse oxidativo. Porém, mecanismos cerebrais tamponam e desconhecemos o resultado dessas interações na estrutura cerebral. Níveis de BDNF não foram influenciados significativamente por metilfenidato em crianças com TDAH, quando comparados a controles em nossa metanálise.

This study evaluated the impact of methylphenidate hydrochloride (MFD) treatment (MFD) in children with Attention Deficit Hyperactivity Disorder. The study included varied methodology, including a review study about methylphenidate effects on BDNF and an experimental cohort study. The review study followed the PRISMA guidelines and was registered in PROSPERO. In the experimental study, a single-center open cohort was designed, with a convenience sample recruited between the years 2020 and 2022, at the teaching outpatient clinic of the Faculty of Medicine at Viçosa Federal University (UFV-MG). Sample with 62 children, 6 to 14 years old, without previous treatment, diagnosed by a child psychiatrist according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders (DSM5). Eight clinical follow-up visits were carried out, and biological samples were collected in 3 visits: before MFD beginning and after 12- and 24-weeks medication. Sociodemographic data, ADHD symptoms, clinical and psychiatric assessments were performed, as well as intelligence testing by psychology. Biological samples for oxidative markers serum dosages (total antioxidant capacity levels -FRAP -, superoxide dismutase activity - SOD-, catalase - CAT -, glutathione S transferase -GST-, lipid peroxidation and carbonyl proteins levels) were collected of each child in the 3 evaluation moments. Immediate-release methylphenidate was administered at approximately 0.65mg/kg/day. The Shapiro-Wilk and Kolmogorov-Smirnov test was used for normality analysis. Absolute and relative frequencies were used for numeric variables that were described by their means and standard deviations. Tukey's parametric test and variance analysis ANOVA (f) were performed for multiple comparisons in redox parameters and other variables respectively. Redox parameters analysis was performed using GraphPad Prism 7.0 program (GraphPad Software, Inc. San Diego, CA, USA) and other variables using SPSS software (version 23.0 for Windows). Statistical significance was considered at p<0.05. Male was predominant (71%), with a mean age of 8.58 ± 1.91, mother and/or biological father were the householder in most homes. Systolic blood pressure, heart rate and body temperature had significant changes, but without clinical significance. Body mass index showed a statistical difference, with 37%, 19.3% and 21% of the children having a BMI above the expected for their age in assessment 1, 2 and 3 respectively. Combined-ADHD occurred in 58.1% of the children, inattentive in 32.3% and hyperactive/impulsive in 9.7%. Drug treatment adherence was 98.4% (12th week) and 93.5% (24th week). There were no changes in FRAP levels; SOD activity had significant decreased at week 12 compared to baseline activity; CAT activity showed a significant increase at the 24th week compared to 12th week; Significant increase in lipid peroxidation levels at 24th week compared to 12th week. Significant increase in protein carbonyls levels at baseline (before methylphenidate use) compared to levels at 12 and 24 weeks. Methylphenidate can influence the oxidative and antioxidative parameters of ADHD children, increasing oxidative stress. However, buffer brain mechanisms may act and the result of these interactions in brain structure is not completely known. BDNF levels were not significantly affected by methylphenidate treatment in ADHD children and do not differ from controls in our meta-analysis.

Oxidative activity of corpus luteum and ovarian parenchyma in Bos taurus indicus heifers

The aim of this study was to evaluate the oxidative stress in ovaries and corpus luteum (CL) of Bos taurus indicus females and the oxidant effect of CL in ovarian tissues in regions near, intermediate, or distant from it. Ovaries (n=12) of Nelore heifers (n=6) were collected from a slaughterhouse and fragmented. Experiment 1, each ovary was obtained from three fragments, resulting in 18 fragments of ovaries with CL (OV+CL) and another 18 fragments of ovaries without CL (OV-CL). Three fragments were generated from CL, totaling 18 CL fragments. In experiment 2, the ovarian fragments were removed from specific regions near, intermediate, or distant from the CL. All the fragments were placed in Eppendorf-type microtubes (1 mL), kept in a thermal container at 4 ºC, and then stored in a -80 ºC freezer for analysis of oxidative stress (TBARS and NBT) and antioxidant potential (FRAP and ABTS). In the antioxidant activity analysis, luteal tissues showed more antioxidant activity than ovarian tissue (FRAP = P < 0.0001; ABTS = P < 0.02). In the oxidative stress analysis, CL had lower levels of reactive oxygen species (ROS; TBARS = P < 0.03; NBT = P < 0.0001) than ovarian tissues. There was no difference in antioxidant activity and oxidative stress between the fragments obtained from different regions (OV+CL versus OV-CL; P > 0.05). The presence of CL in the ovaries of Bos taurus indicus females did not influence the oxidative stress or antioxidant potential of the gonad. Thus, the removal of ovarian fragments with or without the presence of CL indicates that biotechnologies such as in vitro follicle cultivation is possible.(AU)

Interplay of Oxidants and Antioxidants in Mammalian Embryo Culture System.

One principal purpose of assisted reproductive technology (ART) is to produce viable and good quality embryos. However, a variety of environmental factors may induce epigenetic changes in the embryo. Moreover, laboratory conditions including the culture media may also affect embryo development. Therefore, media change is an important factor in maintaining proper oxidant/antioxidant balance during embryo culture. Alterations in the oxidant/antioxidant balance are related to various cellular responses such as an increase in the level of reactive oxygen species (ROS) and consequent lipid peroxidation (LPO), DNA damage, and apoptosis. The current study focuses on the role of external factors on embryo culture and the ability of antioxidants to enhance in vitro fertilization (IVF) outcomes. Indeed, an optimization of media culture by the addition of enzymatic and nonenzymatic antioxidants in animal models and human embryos in ART has been updated in this study, with an emphasis on comparing the available results and their possible reasons.