Improvement of Na+-K+ ATPase Activity and Gene Expression Associated with Glomerular Ultrastructural Protection in Diabetic Nephropathy by Acacia senegal: Role of Oxidative Stress Disturbances / Mejora de la actividad Na+-K+ ATPasa y la Expresión Génica Asociada con la Protección Ultraestructural Glomerular en la Nefropatía Diabética por Acacia senegal: Papel de las Alteraciones del Estrés Oxidativo

SUMMARY: This study assessed the effects of Acacia Senegal (AS) combined with insulin on Na+/K+-ATPase (NKA) activity and mRNA expression, serum glucose, renal function, and oxidative stress in a rat model of diabetic nephropathy (DN). Sixty rats were equally divided into six groups: normal control, normal+AS, diabetic (DM), DM+insulin, DM+AS, and DM+insulin+AS groups. Diabetes mellitus (type 1) was induced by a single injection of streptozotocin (65 mg/kg), and insulin and AS treatments were carried until rats were culled at the end of week 12. Serum glucose and creatinine levels, hemoglobin A1c (HbA1c) were measured. Renal homogenate levels of NKA activity and gene expression, malondialdehyde, superoxide dismutase (SOD), catalase and reduced glutathione (GSH) were evaluated as well as kidney tissue histology and ultrastructure. Diabetes caused glomerular damage and modulation of blood and tissue levels of creatinine, glucose, HbA1c, malondialdehyde, NKA activity and gene expression, SOD, catalase and GSH, which were significantly (p<0.05) treated with AS, insulin, and insulin plus AS. However, AS+insulin treatments were more effective. In conclusion, combined administration of AS with insulin to rats with DN decreased NKA activity and gene expression as well as oxidative stress, and improved glycemic state and renal structure and function.

Este estudio evaluó los efectos de Acacia senegal (AS) combinada con insulina sobre la actividad Na+/K+- ATPasa (NKA) y la expresión de ARNm, la glucosa sérica, la función renal y el estrés oxidativo en un modelo de nefropatía diabética (ND) en ratas. Sesenta ratas se dividieron equitativamente en seis grupos: control normal, normal+AS, diabética (DM), DM+insulina, DM+AS y DM+insulina+AS. La diabetes mellitus (tipo 1) se indujo mediante una única inyección de estreptozotocina (65 mg/kg), y los tratamientos con insulina y AS se llevaron a cabo hasta que las ratas fueron sacrificadas al final de la semana 12. Se midieron niveles séricos de glucosa y creatinina, hemoglobina A1c (HbA1c). Se evaluaron los niveles de homogeneizado renal de actividad NKA y expresión génica, malondialdehído, superóxido dismutasa (SOD), catalasa y glutatión reducido (GSH), así como la histología y ultraestructura del tejido renal. La diabetes causó daño glomerular y modulación de los niveles sanguíneos y tisulares de creatinina, glucosa, HbA1c, malondialdehído, actividad y expresión génica de NKA, SOD, catalasa y GSH, los cuales fueron tratados significativamente (p<0,05) con AS, insulina e insulina más AS. Sin embargo, los tratamientos con AS+insulina fueron más efectivos. En conclusión, la administración combinada de AS con insulina a ratas con DN disminuyó la actividad de NKA y la expresión genética, así como el estrés oxidativo, y mejoró el estado glucémico y la estructura y función renal.

Embryo development is impaired by sperm mitochondrial-derived ROS

BACKGROUND: Basal energetic metabolism in sperm, particularly oxidative phosphorylation, is known to condition not only their oocyte fertilising ability, but also the subsequent embryo development. While the molecular pathways underlying these events still need to be elucidated, reactive oxygen species (ROS) could have a relevant role. We, therefore, aimed to describe the mechanisms through which mitochondrial activity can influence the first stages of embryo development. RESULTS: We first show that embryo development is tightly influenced by both intracellular ROS and mitochondrial activity. In addition, we depict that the inhibition of mitochondrial activity dramatically decreases intracellular ROS levels. Finally, we also demonstrate that the inhibition of mitochondrial respiration positively influences sperm DNA integrity, most likely because of the depletion of intracellular ROS formation. CONCLUSION: Collectively, the data presented in this work reveals that impairment of early embryo development may result from the accumulation of sperm DNA damage caused by mitochondrial-derived ROS.

Efectos de inducción recíproca entre periodontitis e hiposalivación: revisión de la literatura / Reciprocal induction effects between periodontitis and hyposalivation: a review of the literature

Muchas investigaciones se han ocupado de evaluar la vinculación entre las afecciones bucales y otras funciones o afecciones del organismo. Algunos de esos estudios han sentado precedentes acerca de la influencia mutua que puede existir entre la fun-cionalidad de las glándulas salivales y la enfermedad periodontal, y cómo la presencia de una condición puede modificar la evolución o inducir la aparición de la otra. El objetivo del presente trabajo es hacer una revisión bibliográfica de las publicaciones cientí-ficas que evalúan los efectos de inducción recíproca que existe entre la enfermedad periodontal y la hi-posalivación. Trabajos de nuestro grupo y de otros autores demuestran que la hiposalivación reduce la capacidad del organismo para defenderse contra las bacterias patógenas, mantener un ambiente sa-ludable y facilitar la cicatrización en la cavidad bu-cal, promoviendo los procesos de inflamación y daño tisular gingivoperiodontal. A su vez, varios estudios reportan que la enfermedad periodontal induce cam-bios en las glándulas salivales y altera el volumen de secreción salival. Por su parte, el sistema endo-cannabinoide (SEC) muestra estar involucrado tanto en el proceso de secreción salival como en la infla-mación y la reabsorción ósea presentes en la enfer-medad periodontal, en tanto que la activación de los mecanismos del SEC emerge como una de las vías a través de las cuales se desarrollaría el fenómeno de inducción recíproca (AU)

Many investigations have focused on evaluating the link between oral conditions and other functions or conditions of the body. Some of these studies have set precedents about the mutual influence that may exist between the functionality of the salivary glands and periodontal disease, and how the presence of one condition can modify the evolution or induce the appearance of the other. The objective of this work is to carry out a bibliographic review of scientific publications that evaluate the reciprocal induction effects that exist between periodontal disease and hyposalivation. Studies by our group and other authors show that hyposalivation reduces the capacity of the organism to defend itself against pathogenic bacteria, maintain a healthy environment and facilitate healing in the oral cavity, promoting inflammation and gingivoperiodontal tissue damage. In turn, several studies report that periodontal disease induces changes in the salivary glands and alters the volume of salivary secretion. In turn, the endocannabinoid system (ECS) is shown to be involved in the salivary secretion process as well as in the inflammation and bone resorption present in periodontal disease, while the activation of ECS mechanisms emerges as one of the pathways through which the reciprocal induction phenomenon would develop (AU)

Activation of M1 muscarinic acetylcholine receptors by proline-rich oligopeptide 7a (

Background: The bioactive peptides derived from snake venoms of the Viperidae family species have been promising as therapeutic candidates for neuroprotection due to their ability to prevent neuronal cell loss, injury, and death. Therefore, this study aimed to evaluate the cytoprotective effects of a synthetic proline-rich oligopeptide 7a (PRO-7a; <EDGPIPP) from Bothrops jararaca snake, on oxidative stress-induced toxicity in neuronal PC12 cells and astrocyte-like C6 cells. Methods: Both cells were pre-treated for four hours with different concentrations of PRO-7a, submitted to H2O2-induced damage for 20 h, and then the oxidative stress markers were analyzed. Also, two independent neuroprotective mechanisms were investigated: a) L-arginine metabolite generation via argininosuccinate synthetase (AsS) activity regulation to produce agmatine or polyamines with neuroprotective properties; b) M1 mAChR receptor subtype activation pathway to reduce oxidative stress and neuron injury. Results: PRO-7a was not cytoprotective in C6 cells, but potentiated the H2O2-induced damage to cell integrity at a concentration lower than 0.38 μM. However, PRO-7a at 1.56 µM, on the other hand, modified H2O2-induced toxicity in PC12 cells by restoring cell integrity, mitochondrial metabolism, ROS generation, and arginase indirect activity. The α-Methyl-DL-aspartic acid (MDLA) and L-NΩ-Nitroarginine methyl ester (L-Name), specific inhibitors of AsS and nitric oxide synthase (NOS), which catalyzes the synthesis of polyamines and NO from L-arginine, did not suppress PRO-7a-mediated cytoprotection against oxidative stress. It suggested that its mechanism is independent of the production of L-arginine metabolites with neuroprotective properties by increased AsS activity. On the other hand, the neuroprotective effect of PRO-7a was blocked in the presence of dicyclomine hydrochloride (DCH), an M1 mAChR antagonist. Conclusions: For the first time, this work provides evidence that PRO-7a-induced neuroprotection seems to be mediated through M1 mAChR activation in PC12 cells, which reduces oxidative stress independently of AsS activity and L-arginine bioavailability.(AU)

Breviscapine alleviates myocardial ischemia-reperfusion injury in diabetes rats

Purpose: To investigate the protective effect of breviscapine on myocardial ischemia-reperfusion injury (MIRI) in diabetes rats. Methods: Forty rats were divided into control, diabetes, MIRI of diabetes, and treatment groups. The MIRI of diabetes model was established in the latter two groups. Then, the treatment group was treated with 100 mg/kg breviscapine by intraperitoneal injection for 14 consecutive days. Results: After treatment, compared with MIRI of diabetes group, in treatment group the serum fasting blood glucose, fasting insulin, homeostasis model assessment of insulin resistance, and glycosylated hemoglobin levels decreased, the serum total cholesterol, triacylglycerol, and low-density lipoprotein cholesterol levels decreased, the serum high-density lipoprotein cholesterol level increased, the heart rate decreased, the mean arterial pressure, left ventricular ejection fraction, and fractional shortening increased, the serum cardiac troponin I, and creatine kinase-MB levels decreased, the myocardial tumor necrosis factor α and interleukin-6 levels decreased, the myocardial superoxide dismutase level increased, and the myocardial malondialdehyde level decreased (all P < 0.05). Conclusions: For treating MIRI of diabetes in rats, the breviscapine can reduce the blood glucose and lipid levels, improve the cardiac function, reduce the myocardial injury, and decrease the inflammatory response and oxidative stress, thus exerting the alleviating effect.

Dietary total antioxidant capacity, cardiovascular risk, and anthropometric obesity indices in hemodialysis patients: A case-control study / Capacidade antioxidante total da dieta, risco cardiovascular e índices antropométricos de obesidade em pacientes em hemodiálise: um estudo de caso-controle

ABSTRACT Objective: Oxidative stress is triggered by malnutrition and antioxidant losses due to dialysis in hemodialysis patients and thus, oxidative stress increases the risk of mortality in patients with cardiovascular disease and obesity. The study aims to determine differences in cardiovascular risk scores and obesity indices between hemodialysis and control groups and to examine the relationship between the tertiles of dietary total antioxidant capacity with cardiovascular risk, and obesity in hemodialysis and control groups. Methods: This is a cross-sectional case-control study involving hemodialysis patients (n=46) and healthy individuals (n=46). Participants' general characteristics were obtained via a questionnaire, and the Framingham Risk Score was calculated. The dietary total antioxidant capacity was calculated using two methods based on a seven-day food record. Obesity indices, such as Basal Metabolism Index and Body Shape Index, were calculated using anthropometric measurements. Results: The mean age of the participants was 51.1±10.4 years. In the hemodialysis group, obesity indices including body weight, Basal Metabolism Index, waist circumference, fat mass index, and fat-free mass index were lower, while Framingham Risk Score values ​​were higher than the control group (p<0.05). Energy-adjusted dietary total antioksidant capacity values were lower ​​in hemodialysis group, and most patients were in the low tertiles of Trolox equivalent antioxidant capacity, total radical-trapping antioxidant parameter, ferric reducing-antioxidant power and vitamin C equivalent antioxidant capacity (p<0.05). Conclusion: Providing hemodialysis patients with a healthy diet can increase the dietary total antioxidant capacity, and potentially reduce cardiovascular risk, and obesity indices.

RESUMO Objetivo: O estresse oxidativo é desencadeado pela desnutrição e perdas de antioxidantes devido à diálise em pacientes em hemodiálise, portanto, o estresse oxidativo aumenta o risco de mortalidade em pacientes com doenças cardiovasculares e obesidade. O estudo visa determinar as diferenças nos escores de risco cardiovascular e índices de obesidade entre os grupos de hemodiálise e controle, bem como examinar a relação entre os tercis da capacidade antioxidante total da dieta e o risco cardiovascular e obesidade nos grupos de hemodiálise e controle. Métodos: Este é um estudo transversal de caso-controle envolvendo pacientes em hemodiálise (n=46) e indivíduos saudáveis (n=46). As características gerais dos participantes foram obtidas por meio de um questionário, e o Escore de Risco de Framingham foi calculado. A capacidade antioxidante total da dieta foi calculada utilizando dois métodos baseados em um registro alimentar de sete dias. Índices de obesidade como o Índice de Metabolismo Basal e o Índice de Forma Corporal, foram calculados por meio de medidas antropométricas. Resultados: A média de idade dos participantes foi de 51.1±10.4 anos. No grupo de hemodiálise, os índices de obesidade, incluindo peso corporal, Índice de Metabolismo Basal, circunferência da cintura, índice de massa gorda e índice de massa livre de gordura, foram menores, enquanto os valores do Escore de Risco de Framingham foram maiores do que no grupo controle (p<0.05). Os valores de dTAC ajustados pela energia foram menores no grupo de foram hemodiálise, e a maioria dos pacientes estava nos tercis mais baixos de Capacidade antioxidante equivalente ao Trolox, parâmetro antioxidante total de captura de radicais, poder antioxidante redutor férrico e capacidade antioxidante equivalente à vitamina C (p <0.05). Conclusão: Fornecer aos pacientes em hemodiálise uma dieta saudável pode aumentar a capacidade antioxidante total da dieta, reduzindo potencialmente o risco cardiovascular e os índices de obesidade.

Columbianadin ameliorates experimental acute reflux esophagitis in rats via suppression of NF-κB pathway

Purpose: Reflux esophagitis is a condition characterized by inflammation and irritation of the esophagus, resulting from the backflow of stomach acid and other gastric contents into the esophagus. Columbianadin is a coumarin derivative that exhibits anti-inflammatory and antioxidant effects. In this study, we tried to scrutinize the protective effect of Columbianadin against acute reflux esophagitis in rats. Methods: RAW 264.7 cells were utilized to assess cell viability and measure the production of inflammatory parameters. The rats received anesthesia, and reflux esophagitis was induced via ligation of pylorus and fore stomach and corpus junction. Rats received the oral administration of Columbianadin (25, 50 and 100 mg/kg) and omeprazole (20 mg/kg). The gastric secretion volume, acidity, and pH were measured. Additionally, the levels of oxidative stress parameters, cytokines, and inflammatory markers were determined. At the end of the study, mRNA expression was assessed. Results: Columbianadin remarkably suppressed the cell viability and production of tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß, IL-6, cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and prostaglandin (PGE2). Columbianadin treatment remarkably suppressed the secretion of gastric volume, total acidity and enhanced the pH level in the stomach. Columbianadin remarkably altered the level of hydrogen peroxidase, free iron, calcium, and plasma scavenging activity, sulfhydryl group; oxidative stress parameters like malonaldehyde, glutathione, superoxide dismutase, catalase, glutathione peroxidase; inflammatory cytokines viz., TNF-α, IL-6, IL-1ß, IL-10, IL-17, and monocyte chemoattractant protein-1; inflammatory parameters including PGE2, iNOS, COX-2, and nuclear kappa B factor (NF-κB). Columbianadin remarkably (P < 0.001) suppressed the mRNA expression TNF-α, IL-6, IL-1ß and plasminogen activator inhibitor-1. Conclusions: Columbianadin demonstrated a protective effect against acute reflux esophagitis via NF-κB pathway.

XinJiaCongRongTuSiZiWan protects triptolide-induced rats from oxidative stress injury via mitophagy mediated PINK1/Parkin signaling pathway

Purpose: XinJiaCongRongTuSiZiWan (XJCRTSZW) is a traditional Chinese medicine compound for invigorating the kidney, nourishing blood, and promoting blood circulation. This study aimed to explore the effect of XJCRTSZW on triptolide (TP)-induced oxidative stress injury. Methods: Adult female Sprague-Dawley rats and human ovarian granulosa cell lines were treated with TP and XJCRTSZW. Hematoxylin and eosin staining, enzyme-linked immunosorbent assay, flow cytometry, CCK-8, JC-1 staining, transmission electron microscopy, reverse transcription-quantitative polymerase chain reaction, and Western blotting were performed in this study. Results: XJCRTSZW treatment observably ameliorated the TP-induced pathological symptoms. Furthermore, XJCRTSZW treatment observably enhanced the TP-induced reduction of estradiol, anti-Mullerian hormone, progesterone, superoxide dismutase, ATP content, mitochondrial membrane potential, p62, and Hsp60 mRNA, and protein levels in vivo and in vitro (p < 0.05). However, TP-induced elevation of follicle stimulating hormone and luteinizing hormone concentrations, malondialdehyde levels, reactive oxygen species levels, apoptosis rate, mitophagy, and the mRNA and protein expressions of LC3-II/LC3-I, PTEN-induced kinase 1 (PINK1), and Parkin were decreased (p < 0.05). In addition, XJCRTSZW treatment markedly increased cell viability in vitro (p < 0.05). Conclusions: XJCRTSZW protects TP-induced rats from oxidative stress injury via the mitophagy-mediated PINK1/Parkin pathway.

Eucommia granules activate Wnt/ß-catenin pathway, and improve oxidative stress, inflammation, and endothelial injury in preeclampsia rats

Purpose: Pre-eclampsia (PE) is a pregnancy-related complication. Eucommia is effective in the treatment of hypertensive disorders in pregnancy, but the specific effects and possible mechanisms of Eucommia granules (EG) in PE remain unknown. The aim of this study was to investigate the effects and possible mechanisms of EG in PE rats. Methods: Pregnant Sprague Dawley rats were divided into five groups (n = 6): the control group, the model group, the low-dose group, the medium-dose group, and the high-dose group of EG. The PE model was established by subcutaneous injection of levonitroarginine methyl ester. Saline was given to the blank and model groups, and the Eucommia granules were given by gavage to the remaining groups. Blood pressure and urinary protein were detected. The body length and weight of the pups and the weight of the placenta were recorded. Superoxide dismutase (SOD) activity and levels of malondialdehyde (MDA), placental growth factor (PIGF), and soluble vascular endothelial growth factor receptor-1 (sFIt-1) were measured in the placenta. Pathological changes were observed by hematoxylin-eosin staining. Wnt/ß-catenin pathway-related protein expression was detected using Western blot. Results: Compared with the model group, the PE rats treated with EG had lower blood pressure and urinary protein. The length and weight of the pups and placental weight were increased. Inflammation and necrosis in the placental tissue was improved. SOD level increased, MDA content and sFIt-1/PIGF ratio decreased, and Wnt/ß-catenin pathway-related protein expression level increased. Moreover, the results of EG on PE rats increased with higher doses of EG. Conclusions: EG may activate the Wnt/ß-catenin pathway and inhibit oxidative stress, inflammation, and vascular endothelial injury in PE rats, thereby improving the perinatal prognosis of preeclamptic rats. EG may inhibit oxidative stress, inflammation, and vascular endothelial injury through activation of the Wnt/ß-catenin pathway in preeclampsia rats, thereby improving perinatal outcomes in PE rats.

Impairment of Autophagic Flux After Hypobaric Hypoxia Potentiates Oxidative Stress and Cognitive Function Disturbances in Mice / 神经科学通报·英文版

Acute hypobaric hypoxic brain damage is a potentially fatal high-altitude sickness. Autophagy plays a critical role in ischemic brain injury, but its role in hypobaric hypoxia (HH) remains unknown. Here we used an HH chamber to demonstrate that acute HH exposure impairs autophagic activity in both the early and late stages of the mouse brain, and is partially responsible for HH-induced oxidative stress, neuronal loss, and brain damage. The autophagic agonist rapamycin only promotes the initiation of autophagy. By proteome analysis, a screen showed that protein dynamin2 (DNM2) potentially regulates autophagic flux. Overexpression of DNM2 significantly increased the formation of autolysosomes, thus maintaining autophagic flux in combination with rapamycin. Furthermore, the enhancement of autophagic activity attenuated oxidative stress and neurological deficits after HH exposure. These results contribute to evidence supporting the conclusion that DNM2-mediated autophagic flux represents a new therapeutic target in HH-induced brain damage.

Oxidative and osmotolerant effects in Salvator merianae (Squamata: Teiidae) red blood cells during hibernation / Efeitos de oxidação e osmotolerância dos eritrócitos de Salvator merianae (Squamata: Teiidae) durante a hibernação

Abstract Hibernation is a natural condition of animals that lives in the temperate zone, although some tropical lizards also experience hibernation annually, such as the lizard native from South America, Salvator merianae, or "tegu" lizard. Even though physiological and metabolic characteristic associated with hibernation have been extensively studied, possible alterations in the red blood cells (RBC) integrity during this period remains unclear. Dehydration and fasting are natural consequences of hibernating for several months and it could be related to some cellular modifications. In this study, we investigated if the osmotic tolerance of RBCs of tegu lizard under hibernation is different from the cells obtained from animals while normal activity. Additionally, we indirectly investigated if the RBCs membrane of hibernating tegus could be associated with oxidation by quantifying oxidized biomolecules and the activity of antioxidant enzymes. Our findings suggest that RBCs are more fragile during the hibernation period, although we did not find evidence of an oxidative stress scenario associated with the accentuated fragility. Even though we did not exclude the possibility of oxidative damage during hibernation, we suggested that an increased RBCs volume as a consequence of hypoosmotic blood during hibernation could also affect RBCs integrity as noted.

Resumo A hibernação é uma condição natural dos animais que vivem na zona temperada, embora alguns lagartos tropicais também experenciem hibernação anualmente, como é o caso do lagarto nativo da América do Sul, Salvator merianae ou "teiú". Embora as características fisiológicas e metabólicas associadas à hibernação tenham sido amplamente estudadas, possíveis alterações na integridade das hemácias durante esse período ainda permanecem obscuras. A desidratação e o jejum são consequências naturais da hibernação por vários meses e podem estar relacionadas a algumas modificações celulares. Neste estudo, investigamos se a tolerância osmótica de hemácias do lagarto teiú sob hibernação são diferentes das células obtidas de animais em atividade normal. Além disso, investigamos indiretamente por meio da quantificação de biomoléculas oxidadas e da atividade de enzimas antioxidantes se a membrana das hemácias dos teiús em hibernação poderia estar associada à oxidação. Nossos resultados sugerem que as hemácias possuem maior fragilidade durante o período de hibernação, embora não tenhamos encontrado evidências de um cenário de estresse oxidativo associado à essa fragilidade acentuada. Embora não tenhamos excluído a possibilidade de dano oxidativo durante a hibernação, sugerimos que um aumento no volume das hemácias como consequência de sangue hipoosmótico durante a hibernação também poderia afetar a integridade de hemácias, tal como foi observado.

Development of chitosan based microencapsulated spray dried powder of tuna fish oil: oil load impact and oxidative stability / Desenvolvimento de pó microencapsulado por pulverização de óleo de atum à base de quitosana: impacto da carga de óleo e estabilidade oxidativa

Abstract The impact of fish oil concentration on the oxidative stability of microcapsules through the spray drying process using chitosan and maltodextrin as wall material was studied. Emulsions were prepared with different Tuna fish oil (TFO) content (TFO-10%, TFO20%, TF030% TF0-40%) while wall material concentration was kept constant. Microencapsulated powder resulting from emulsion prepared with high fish oil load have high moisture content, wettability, total oil and low encapsulation efficiency, hygroscopicity and bulk tapped density. Oxidative stability was evaluated periodically by placing microcapsules at room temperature. Microcapsules prepared with TFO-10% presented high oxidative stability in terms of peroxide value (2.94±0.04) and anisidine value (1.54±0.02) after 30 days of storage. It was concluded that optimal amounts of fish oil for microencapsulation are 10% and 20% using chitosan and maltodextrin that extended its shelf life during study period.

Resumo Foi estudado o impacto da concentração de óleo de peixe na estabilidade oxidativa de microcápsulas por meio do processo de secagem por atomização, utilizando quitosana e maltodextrina como material de parede. As emulsões foram preparadas com diferentes teores de óleo de atum (TFO) (TFO-10%, TFO20%, TF030% TF0-40%), enquanto a concentração de material de parede foi mantida constante. O pó microencapsulado resultante da emulsão preparada com alta carga de óleo de peixe tem alto teor de umidade, molhabilidade e óleo total e baixa eficiência de encapsulação, higroscopicidade e densidade extraída a granel. A estabilidade oxidativa foi avaliada periodicamente colocando microcápsulas à temperatura ambiente. As microcápsulas preparadas com TFO-10% apresentaram alta estabilidade oxidativa em termos de valor de peróxido (2,94 ± 0,04) e valor de anisidina (1,54 ± 0,02) após 30 dias de armazenamento. Concluiu-se que as quantidades ideais de óleo de peixe para microencapsulação são de 10% e 20% usando quitosana e maltodextrina que prolongaram sua vida útil durante o período de estudo.

Interleukin-37 has A Promising Cardioprotective Effect on Isoproterenol-Induced Myocardial Infarction / La Interleucina-37 tiene un Efecto Cardioprotector Prometedor sobre el Infarto de Miocardio Inducido por Isoproterenol

SUMMARY: The main cause of mortality and disability globally is myocardial infarction (MI). Isoproterenol (ISO), a β-adrenoceptor agonist, has been used to induce rat myocardial necrosis. Whereas interleukin-37 (IL-37) has anti-inflammatory and cytoprotective properties. The study aimed to investigate the potential protective effects of IL-37 administration on cardiac architecture, oxidative stress, and inflammatory markers during ISO-induced MI in rats. Three groups of adult male rats were used in this study, the normal control group (n=8), ISO-induced MI group (n=8) that received isoproterenol hydrochloride (ISO) (100 mg/kg/day, SC, for the first 2 consecutive days), and IL-37-treated group (ISO+IL-37) (n=8) that received recombinant human IL-37 (40 µg/kg /day, intraperitoneally, for 2 weeks during and after ISO injections. Heart rate (HR.) and ECG changes were monitored. Some oxidative stress markers such as superoxide dismutase (SOD), nitric oxide (NOx), malondialdehyde (MDA), and glutathione (GSH) tissue levels in the tissue homogenate were assayed. Interleukin- 6 (IL-6), tumor necrosis factor- α (TNF-α), caspase-8, P53, and C- reactive protein (CRP) were among the inflammatory markers examined. In addition, serum levels of creatinine kinase (CK-MB) and lactate dehydrogenase (LDH) were analyzed to evaluate the myocardial injury. For histological analysis, tissues were sectioned, fixed in paraffin, and stained with hematoxylin and eosin (H&E), Masson Trichrome and, immunohistochemical against NF-kB, TNF-α, and Caspase-9. IL-37 improved ECG changes, cardiac enzyme markers, and some inflammatory markers of oxidative stress in ISO-induced MI. It also improved the histopathological and immunohistochemical changes in MI. In conclusion: IL-37 might be a promising therapeutic modality in myocardial infarction.

La principal causa de mortalidad y discapacidad a nivel mundial es el infarto de miocardio (IM). El isoproterenol (ISO), un agonista de los receptores adrenérgicos β, se ha utilizado para inducir necrosis miocárdica en ratas. Mientras que la interleucina-37 (IL-37) tiene propiedades antiinflamatorias y citoprotectoras. El estudio tuvo como objetivo investigar los posibles efectos protectores de la administración de IL-37 en la arquitectura cardíaca, el estrés oxidativo y los marcadores inflamatorios durante el infarto de miocardio inducido por ISO en ratas. En este estudio se utilizaron tres grupos de ratas macho adultas, el grupo control normal (n=8), el grupo con IM inducido por ISO (n=8) que recibió clorhidrato de isoproterenol (ISO) (100 mg/kg/día, SC, durante los primeros 2 días consecutivos) y el grupo tratado con IL-37 (ISO+IL- 37) (n=8) que recibió IL-37 humana recombinante (40 µg/kg/día, por vía intraperitoneal, durante 2 semanas durante y después de las inyecciones de ISO. Se monitorearon la frecuencia cardíaca (FC) y los cambios en el ECG. Se analizaron algunos marcadores de estrés oxidativo como la superóxido dismutasa (SOD), el óxido nítrico (NOx), el malondialdehído (MDA) y los niveles tisulares de glutatión (GSH) en el homogeneizado de tejido. La interleucina-6 (IL-6), el factor de necrosis tumoral-α (TNF-α), la caspasa-8, la P53 y la proteína C reactiva (CRP) se encontraban entre los marcadores inflamatorios examinados. Se analizaron los niveles de creatinoquinasa (CK-MB) y lactato deshidrogenasa (LDH) para evaluar la lesión miocárdica; para el análisis histológico se seccionaron los tejidos, se fijaron en parafina y se tiñeron con hematoxilina y eosina (H&E), Tricromo de Masson e inmunohistoquímica contra NF-kB, TNF-α y Caspasa-9. IL-37 mejoró los cambios de ECG, los marcadores de enzimas cardíacas y algunos marcadores inflamatorios de estrés oxidativo en el IM inducido por ISO. Además mejoró los cambios histopatológicos e inmunohistoquímicos en MI. En conclusión: la IL-37 podría ser una modalidad terapéutica prometedora en el infarto de miocardio.

The Effects of White Tea (Camellia Sinensis) and Infliximab Against Cisplatin- Induced Testicular Damage via Oxidative Stress and Apoptosis / Efectos del Té Blanco (Camellia Sinensis) e Infliximab Contra el Daño Testicular Inducido por Cisplatino a Través del Estrés Oxidativo y la Apoptosis

SUMMARY: Cisplatin (Cis) is an important chemotherapeutic agent used in cancer treatment. Males exposed to Cis were reported to exhibit testicular toxicity. Cis-induced testicular toxicity is mediated by oxidative stress, inflammation, testosterone inhibition and apoptosis. Accordingly, this study was conducted to evaluate the potential protective roles of infliximab (IFX), which is an anti- TNF-a agent, and of white tea (Camellia sinensis), which is known to possess antioxidant, anti-apoptotic, and anti-inflammatory effects, against Cis-induced testicular toxicity in rats. Rats were randomly assigned into five groups as follows: control group, Cisplatin (7 mg/kg) treatment group, Cisplatin (7 mg/kg) + infliximab (7 mg/kg) treatment group, cisplatin + white tea (WT) treatment group, and Cisplatin+ WT+IFX combined treatment group. In the present study, Cis exposure reduced the sperm count. It also increased testicular oxidative stress as well as the levels of inflammatory and apoptotic markers. Histopathological assays supported the biochemical findings. Treatment with IFX and/or WT restored testicular histology, preserved spermatogenesis, suppressed oxidative stress and apoptosis, and significantly ameliorated Cis-induced damage. It was concluded that white tea and infliximab could potentially serve as therapeutic options for the protection of testicular tissue against the harmful effects of Cis.

El cisplatino (Cis) es un importante agente quimioterapéutico utilizado en el tratamiento del cáncer. Se informó que los hombres expuestos a Cis exhibieron toxicidad testicular. La toxicidad testicular inducida por Cis está mediada por el estrés oxidativo, la inflamación, la inhibición de la testosterona y la apoptosis. En consecuencia, este estudio se realizó para evaluar las posibles funciones protectoras de infliximab (IFX), un agente anti-TNF-α, y del té blanco (Camellia sinensis), conocido por sus propiedades antioxidantes, antiapoptóticas y anti-TNF-α -efectos inflamatorios, contra la toxicidad testicular inducida por Cis en ratas. Cinco grupos de ratas se asignaron al azar de la siguiente manera: grupo control, grupo de tratamiento con cisplatino (7 mg/ kg), grupo de tratamiento con cisplatino (7 mg/kg) + infliximab (7 mg/kg), grupo de tratamiento con cisplatino + té blanco (WT), y grupo de tratamiento combinado Cisplatino+ WT+IFX. En el presente estudio, la exposición a Cis redujo el conteo de espermatozoides. También aumentó el estrés oxidativo testicular, así como los niveles de marcadores inflamatorios y apoptóticos. Los ensayos histopatológicos respaldaron los hallazgos bioquímicos. El tratamiento con IFX y/o WT restauró la histología testicular, preservó la espermatogénesis, suprimió el estrés oxidativo y la apoptosis, y mejoró significativamente el daño inducido por Cis. Se concluyó que el té blanco y el infliximab podrían potencialmente servir como opciones terapéuticas para la protección del tejido testicular contra los efectos nocivos de Cis.

Genética y genómica de la longevidad y el envejecimiento / Genetics and genomics of longevity and aging

El envejecimiento y la longevidad son procesos que involucran una serie de factores genéticos, bioquímicos y ambientales. En esta revisión se tratan algunas cuestiones sobre estos dos procesos biológicos y epigenéticos. Se presentan los genes más importantes en estos procesos, así como se ejemplifican enfermedades que presentan un aceleramiento o falla en la longevidad y el envejecimiento. Se usa el análisis inteligente de datos para hallar interacciones de proteínas/genes que expliquen estos dos fenómenos biológicos.

Aging and longevity are processes that involve a series of genetic, biochemical and environmental factors. This review addresses some issues about these two biological and epigenetic processes. The most important genes in these processes are presented, as well as diseases that present an acceleration or failure in longevity and aging. Intelligent data analysis is used to find protein/gene interactions that explain these two biological phenomena.

The antioxidant effect of preischemic dexmedetomidine in a rat model: increased expression of Nrf2/HO-1 via the PKC pathway

Abstract Background The precise underlying mechanism of antioxidant effects of dexmedetomidine-induced neuroprotection against cerebral ischemia has not yet been fully elucidated. Activation of Nuclear factor erythroid 2-related factor (Nrf2) and Heme Oxygenase-1 (HO-1) represents a major antioxidant-defense mechanism. Therefore, we determined whether dexmedetomidine increases Nrf2/HO-1 expression after global transient cerebral ischemia and assessed the involvement of Protein Kinase C (PKC) in the dexmedetomidine-related antioxidant mechanism. Methods Thirty-eight rats were randomly assigned to five groups: sham (n = 6), ischemic (n = 8), chelerythrine (a PKC inhibitor; 5 mg.kg-1 IV administered 30 min before cerebral ischemia) (n = 8), dexmedetomidine (100 µg.kg-1 IP administered 30 min before cerebral ischemia (n = 8), and dexmedetomidine + chelerythrine (n = 8). Global transient cerebral ischemia (10 min) was applied in all groups, except the sham group; histopathologic changes and levels of nuclear Nrf2 and cytoplasmic HO-1 were examined 24 hours after ischemia insult. Results We found fewer necrotic and apoptotic cells in the dexmedetomidine group relative to the ischemic group (p< 0.01) and significantly higher Nrf2 and HO-1 levels in the dexmedetomidine group than in the ischemic group (p< 0.01). Additionally, chelerythrine co-administration with dexmedetomidine attenuated the dexmedetomidine-induced increases in Nrf2 and HO-1 levels (p< 0.05 and p< 0.01, respectively) and diminished its beneficial neuroprotective effects. Conclusion Preischemic dexmedetomidine administration elicited neuroprotection against global transient cerebral ischemia in rats by increasing Nrf2/HO-1 expression partly via PKC signaling, suggesting that this is the antioxidant mechanism underlying dexmedetomidine-mediated neuroprotection.

Biochemical analysis of oxidative stress and purinergic system in pregnant women with gestational diabetes mellitus / Análise bioquímica do estresse oxidativo e do sistema purinérgico em gestantes com diabetes mellitus gestacional

Background: Pregnancy is characterized as a physiological period with greater sensitivity to insulin resistance and changes in oxidative stress. Purinergic signaling is directly related to diabetes, as this condition modifies the concentration of extracellular ATP and the level of degradation of ATP to adenosine. Objective: Analyze oxidative stress and the purinergic system in pregnant women with Gestational Diabetes Mellitus (GDM) and compare them with low-risk pregnant women (LR). Materials and Methods: The research was of a quantitative approach of an experimental nature. The study was carried out at the Clínica da Mulher, which serves high-risk pregnant women, and at the Family Health Centers, which serves low-risk pregnant women, both located in Chapecó, Santa Catarina, Brazil. Results: From the analysis, it was observed that oxidative stress was increased in pregnant women in LR compared to pregnant women with GDM by increasing the concentration of TBARS and reducing the concentration of Carbonyl Protein in pregnant women with LR. Regarding the purinergic system, there was a significant decrease in the hydrolysis of the nucleotides ATP, ADP, and AMP in pregnant women with GDM, and a significant increase in the hydrolysis of ADA, also in pregnant women with GDM. Conclusion: Therefore, pregnant women with GDM have less oxidative stress compared to pregnant women in LR concerning TBARS and Carbonyl Protein markers, thus allowing a greater antioxidant defense mechanism. Furthermore, concerning the purinergic system, there is an increase in the activity of ADA, which is directly related to the immunosuppression process, a necessary condition for the protection of the fetus during the gestational period (AU).

Introdução: A gravidez é caracterizada como um período fisiológico em que há uma maior sensibilidade a resistência à insulina e alterações no estresse oxidativo. A sinalização purinérgica está diretamente relacionada ao diabetes, pois esta condição modifica a concentração de ATP extracelular e o nível de degradação de ATP em adenosina. Objetivo:Analisar o estresse oxidativo e o sistema purinérgico em gestantes com Diabetes Mellitus Gestacional (DMG) e compará-los com gestantes de baixo risco (BR). Materiais e Métodos: A pesquisa foi de abordagem quantitativa, de caráter experimental. O estudo foi realizado na Clínica da Mulher, que atende gestantes de alto risco, e nas Unidades de Saúde da Família, que atendem gestantes de baixo risco, ambas localizadas no município de Chapecó, Santa Catarina, Brasil. Resultados: A partir das análises, observou-se que o estresse oxidativo apresentou-se aumentado em gestantes de BR quando comparado a gestantes com DMG. No que tange ao sistema purinérgico, houve uma diminuição significativa na hidrólise dos nucleotídeos ATP, ADP e AMP em gestantes com DMG, bem como um aumento significativo na hidrólise de ADA, também em gestantes com DMG. Conclusão: Portanto, gestantes com DMG possuem menor estresse oxidativo quando comparado a gestantes de BR, permitindo assim, um maior mecanismo de defesa antioxidante. Para mais, no que se refere ao sistema purinérgico, verifica-se o aumento da concentração de ADA está diretamente relacionada ao processo de imunossupressão, condição necessária à proteção do feto durante o período gestacional (AU).

Diacerein mitigates renal ischemia/reperfusion injury via inhibition of renal inflammation, dendritic cells maturation and apoptosis: the role of TLR4/NF-kB/NLRP3/IL-1beta signaling pathway / La diacereína mitiga la lesión por isquemia/reperfusión renal a través de la inhibición de la inflamación renal, la maduración de las células dendríticas y la apoptosis: el papel de la vía de señalización TLR4/NF-kB/NLRP3/IL-1beta

SUMMARY: One of the reasons for acute kidney damage is renal ischemia. Nevertheless, there are limited protective and therapeutic approaches for this problem. Diacerein is an anti-inflammatory drug characterized by numerous biological activities. We aimed to determine the ameliorative impact of diacerein on renal ischemia/reperfusion injury (I/R) condition, exploring the underlying mechanisms. Twenty-four male rats were allotted into four groups (n= 6): sham group; Diacerein (DIA) group; I/R group, in which a non-crushing clamp occluded the left renal pedicle for 45 min, and the right kidney was nephrectomized for 5 min before the reperfusion process; I/R + diacerein group, injected intraperitoneally with 50 mg diacerein/kg i.m 30 minutes prior to I/R operation. Ischemia/ reperfusion was found to affect renal function and induce histopathological alterations. The flow cytometry analysis demonstrated an elevated expression of innate and mature dendritic cells in I/R renal tissues. Moreover, upregulation in the expression of the inflammatory genes (TLR4, Myd88, and NLRP3), and overexpression of the pro-inflammatory cytokines (IL-1β), apoptotic (caspase-3) and pyroptotic (caspase-1) markers were observed in I/R-experienced animals. The aforementioned deteriorations were mitigated by pre-I/R diacerein treatment. Diacerein alleviated I/R-induced inflammation and apoptosis. Thus, it could be a promising protective agent against I/R.

La isquemia renal es una de los motivos del daño renal agudo. Sin embargo, los enfoques protectores y terapéuticos para este problema son limitados. La diacereína es un fármaco antiinflamatorio caracterizado por numerosas actividades biológicas. Nuestro objetivo fue determinar el impacto de mejora de la diacereína en la condición de lesión por isquemia/ reperfusión renal (I/R), explorando los mecanismos subyacentes. Veinticuatro ratas macho se distribuyeron en cuatro grupos (n= 6): grupo simulado; grupo de diacereína (DIA); grupo I/R, en el que una pinza no aplastante ocluyó el pedículo renal izquierdo durante 45 min, y el riñón derecho fue nefrectomizado durante 5 min antes del proceso de reperfusión; Grupo I/R + diacereína, inyectado por vía intraperitoneal con 50 mg de diacereína/kg i.m. 30 min antes de la operación I/R. Se encontró que la isquemia/ reperfusión afecta la función renal e induce alteraciones histopatológicas. El análisis de citometría de flujo demostró una expresión elevada de células dendríticas innatas y maduras en tejidos renales I/R. Además, se observó una regulación positiva en la expresión de los genes inflamatorios (TLR4, Myd88 y NLRP3) y una sobreexpresión de las citoquinas proinflamatorias (IL-1β), marcadores apoptóticos (caspasa-3) y piroptóticos (caspasa-1) en animales con experiencia en I/R. Los deterioros antes mencionados fueron mitigados por el tratamiento previo a la diacereína I/R. La diacereína alivió la inflamación y la apoptosis inducidas por I/R. Por lo tanto, podría ser un agente protector prometedor contra I/R.

Ozonoterapia y cáncer: mito o realidad / Ozone Therapy and Cancer: Myth or Reality

Introducción: El uso clínico de la ozonoterapia se incrementa cada día. Abarca disímiles especialidades médicas como la oncología. En Cuba las investigaciones que evalúan el empleo de la ozonoterapia en pacientes con cáncer son escasas, se precisan estudios científicos que demuestren su eficacia clínica. Objetivo: Explicar los mecanismos farmacológicos y bioquímicos de la ozonoterapia y su uso en el cáncer como terapia complementaria. Métodos: Se consultaron bases de datos disponibles a través de la red de Infomed. Se utilizaron como palabras clave: cáncer, ozonoterapia y estrés oxidativo. Se seleccionaron artículos originales y de revisión sistemáticos de los últimos diez años que evaluaron la utilización de la ozonoterapia en el tratamiento del cáncer. Resultados: El cáncer es per se una enfermedad inductora de estrés oxidativo. La ozonoterapia respalda su utilización como una terapia adyuvante mediante el preacondicionamiento oxidativo que estimula los sistemas antioxidantes de la célula contra la acción de los radicales libres. Así, se logra neutralizar la acción nociva del estrés oxidativo. El ozono incrementa la eficacia de la radio - quimioterapia y ayuda a reducir los efectos secundarios de estos tratamientos al activar los sistemas antioxidantes de la célula. La ozonoterapia se caracteriza por la simplicidad de su aplicación, bajos costos, alta efectividad y prácticamente ausencia de efectos colaterales en comparación con otros tratamientos adyuvantes. Conclusiones: El uso de la ozonoterapia en oncología como una terapia adyuvante representó un recurso terapéutico de gran valor dado por su perfil de efectividad y seguridad. Su uso podría extenderse para disminuir los efectos secundarios y mejorar la calidad de vida de los pacientes(AU)

Introduction: The clinical use of ozone therapy is increasing every day worldwide and it covers different medical specialties, including oncology. However, in Cuba, the investigations that evaluate the use of ozone therapy in cancer patients are scarce, so scientific studies are needed to demonstrate its clinical efficacy. Objective: To explain the pharmacological and biochemical mechanisms of ozone therapy and its use in cancer as a complementary therapy. Methods: Databases available through Infomed Network were consulted. Key words used were cancer, ozone therapy and oxidative stress. Original and systematic review articles from the last ten years that evaluated the use of ozone therapy in the treatment of cancer were selected. Results: Cancer is, as such, a disease that induces oxidative stress. Ozone therapy supports its use as an adjuvant therapy through oxidative pre-conditioning that stimulates the cell's antioxidant systems against the action of free radicals. Thus, it is possible to neutralize the harmful action of oxidative stress. Ozone increases the efficacy of radio-chemotherapy and helps reducing the side effects of these treatments by activating the cell's antioxidant systems. Ozone therapy is characterized by the simplicity of its application, low costs, high effectiveness and with practically no side effects, compared to other adjuvant treatments. Conclusions: The use of ozone therapy in oncology as an adjuvant therapy represented a therapeutic resource of great value given its effectiveness and safety profile. Its use could be extended to improve tissue oxygenation and thus enhance the efficacy of radiochemotherapy, reducing side effects and improving the patients's quality of life(AU)

Potencial inibitório do ácido elágico sobre a formação do complexo Keap1-Nrf2: implicações terapêuticas em doenças crônico-degenerativas / Inhibitory potential of ellagic acid on the formation of the keap1-Nrf2 complex: Therapeutical implications in chronic-degenerative diseases

Objetivos ­ Avaliar o potencial inibitório do ácido elágico sobre as interações do complexo Keap1-Nrf2, com o intuito de esclarecer um dos eventuais mecanismos associado à atividade antioxidante do ácido elágico. Métodos ­ Foram empregadas simulações de docagem molecular para prever o modo de ligação do ácido elágico no sítio ligante da proteína Keap1, o qual foi comparado com o modo de ligação obtido experimentalmente e descrito na literatura para o ligante natural, a proteína Nrf2, e um potente inibidor monoácido do complexo Keap1-Nrf2. Resultados ­ As simulações de docagem revelaram que o ácido elágico apresenta potencial para realizar uma rede de ligações de hidrogênio com resíduos de aminoácidos da proteína Keap1 considerados importantes para o reconhecimento do Nrf2, se assemelhando ao perfil observado para inibidores do complexo Keap1-Nrf2 descritos na literatura. Conclusão ­ O ácido elágico apresenta características químicas e espaciais favoráveis para a inibição do complexo Keap1-Nrf2 e a elucidação do seu modo de ligação pode auxiliar na identificação de novos produtos naturais com propriedades antioxidantes e potencializar o desenvolvimento de fármacos contra doenças crônico-degenerativas.