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.

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.

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)

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.

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.

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.

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.

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.

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).

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)

Can pumpkin save us of doxorubicin induced cardiotoxicity? / ¿Puede la calabaza salvarnos de la cardiotoxicidad inducida por doxorrubicina?

SUMMARY: Doxorubicin (DOX) is one of the drugs necessary for the treatment of the 10 most common types of cancer. The leading adverse effect limiting clinical use of DOX is cardiotoxicity. Given that literature data indicate a protective role of carotenoids in doxorubicin-induced toxicity, in our study we compared the cardioprotective effect of a mixture of pumpkin carotenoids and a commercially available antioxidant preparation. Animals were distributed in 8 groups (Control - S; NADES - N; Doxorubicin - Dox; Carotenoids - Car; CardiofortIN - CF; NADES-Doxorubicin - N-Dox; Carotenoids-Doxorubicin - Car-Dox; CardiofortIN-Doxorubicin - CF-Dox). Histological sections were stained with the hematoxylin-eosin (HE) and analyzed for the presence of myocardial damage by doxorubicin damage score (DDS). From the heart tissue homogenate were determined the intensity of lipid peroxidation and specific antioxidative enzyme activity (superoxide dismutase; catalase; glutathione S-transferase; glutathione peroxidase). In Car-DOX and CF-DOX groups, lipid peroxidation is significantly reduced compared to DOX group. Pretreatment of animals with carotenoids and in lesser extent with CardiofortIN led to higher antioxidative enzymes activity, compared to DOX group. Pretreated with carotenoids, only 50 % of animals had some degree of myocardial damage, and no animals had extensive damage. CardiofortIN pretreatment showed less protective effect. Pretreatment with carotenoid extract, reduced DDS significantly, so Car-DOX group has changes equivalent to mild myocardial damage. Although CardiofortIN pretreatment lowered DDS score values, animals still had moderate level of myocardium damage. This in vivo study and its findings indicate that carotenoids extracted from pumpkin may be a promising cardioprotective agent against doxorubicin induced cardiotoxicity, at least in part mediated through inhibition of DOX-induced oxidative stress.

La doxorrubicina (DOX) es uno de los fármacos necesarios para el tratamiento de los 10 tipos más comunes de cáncer. El principal efecto adverso que limita el uso clínico de DOX es la cardiotoxicidad. Debido a que los datos de la literatura indican un papel protector de los carotenoides en la toxicidad inducida por doxorrubicina, en nuestro estudio comparamos el efecto cardioprotector de una mezcla de carotenoides de calabaza y una preparación antioxidante disponible comercialmente. Los animales se distribuyeron en 8 grupos (Control - S; NADES - N; Doxorrubicina - Dox; Carotenoides - Car; CardiofortIN - CF; NADES-Doxorrubicina - N-Dox; Carotenoides-Doxorrubicina - Car-Dox; CardiofortIN- Doxorrubicina - CF-Dox). Las secciones histológicas se tiñeron con hematoxilina-eosina (HE) y se analizaron para detectar la presencia de daño miocárdico mediante la puntuación de daño por doxorrubicina (DDS). A partir del homogeneizado de tejido cardíaco se determinó la intensidad de la peroxidación lipídica y la actividad enzimática antioxidante específica (superóxido dismutasa, catalasa, glutatión S-transferasa, glutatión peroxidasa). En los grupos Car-DOX y CF-DOX, la peroxidación lipídica se redujo significativamente en comparación con el grupo DOX. El pre tratamiento de los animales con carotenoides y, en menor medida, con CardiofortlN condujo a una mayor actividad de las enzimas antioxidantes, en comparación con el grupo DOX. Al ser pre tratados con carotenoides, solo el 50 % de los animales tenían algún grado de daño miocárdico y ningún animal tenía daño extenso. El pre tratamiento con CardiofortIN mostró un efecto protector menor. El pre tratamiento con extracto de carotenoides redujo significativamente el DDS, por lo que el grupo Car-DOX mostró cambios equivalentes a un daño miocárdico leve. Aunque el pre tratamiento con CardiofortIN redujo los valores de la puntuación DDS, los animales aún tenían un nivel moderado de daño al miocardio. Este estudio in vivo y sus hallazgos indican que los carotenoides extraídos de la calabaza pueden ser un agente cardioprotector prometedor contra la cardiotoxicidad inducida por doxorrubicina, al menos en parte mediada por la inhibición del estrés oxidativo inducido por DOX.

Exposure to the herbicide atrazine induces oxidative imbalance, morphological damage and decreased survival in juvenile fish

Synthetic herbicides have been intensively used in weed control, although often involved in environmental contamination, critically affecting non-target species. However, never was investigated the effect of commercial formulation using atrazine on developing juvenile fish exposed for 35 days. Juveniles (Astyanax altiparanae) (n = 600) were assigned to the following ATZ-exposed groups: 0 (CTR-control), 0.56 (ATZ0.56), 1.00 (ATZ1.00), 1.66 (ATZ1.66) and 11.66 (ATZ11.66) µg/L. We found a 36.6% decrease in juvenile survival rate in the ATZ11.66 group compared to control and other groups. Juveniles from ATZ11.66 also showed hyperglycemia and increased cortisol levels. Increased the imbalance oxidative with an increase in malondialdehyde (MDA) and Carbonylated proteins levels markers in muscle, gills, and liver. We also found increased activity of the antioxidant enzymes superoxide dismutase (SOD) in gills and SOD and catalase (CAT) in muscles from ATZ11.66 fish, and increased glutathione S-transferase (GST) activities in the liver from all exposed groups compared to control. The morphological consequences of this were loss of secondary lamella integrity, increased mucus-secreting cells, hyperplasia, and lamellar fusion, as well as increased aneurysms percentage. The liver showed vascular congestion associated with endothelial hyperplasia, steatosis, and a decrease in the nuclei percentage. Our results showed that exposure to a commercial formulation of ATZ at 11.66 µg/L can be causing an imbalance in the oxidative markers and morphological damages and decreased survival in a juvenile Neotropical species of great ecological relevance and commercial interest.

Fasudil mediates neuroprotection in ischemia/reperfusion by modulating the ROCK-PPARα-NOX axis

Purpose: Cerebral ischemia-reperfusion (I/R) is a neurovascular disorder that leads to brain injury. In mice, Fasudil improves nerve injury induced by I/R. However, it is unclear if this is mediated by increased peroxisome proliferator-activated receptor-α (PPARα) expression and reduced oxidative damage. This study aimed to investigate the neuroprotective mechanism of action of Fasudil. Methods: MCAO (Middle cerebral artery occlusion) was performed in male C57BL/6J wild-type and PPARα KO mice between September 2021 to April 2023. Mice were treated with Fasudil and saline; 2,3,5-Triphenyltetrazolium chloride (TTC) staining was performed to analyze cerebral infarction. PPARα and Rho-associated protein kinase (ROCK) expression were detected using Western blot, and the expression of NADPH subunit Nox2 mRNA was detected using real-time polymerase chain reaction. The NADPH oxidase activity level and reactive oxygen species (ROS) content were also investigated. Results: After cerebral ischemia, the volume of cerebral necrosis was reduced in wild-type mice treated with Fasudil. The expression of PPARα was increased, while ROCK was decreased. Nox2 mRNA expression, NADPH oxidase activity, and ROS content decreased. There were no significant changes in cerebral necrosis volumes, NADPH oxidase activity, and ROS content in the PPARα KO mice treated with Fasudil. Conclusions: In mice, the neuroprotective effect of Fasudil depends on the expression of PPARα induced by ROCK-PPARα-NOX axis-mediated reduction in ROS and associated oxidative damage.

Neuroprotective potential of sevoflurane against isoflurane induced cognitive dysfunction in rats via anti-inflammatory and antioxidant effect

Purpose: Intravenous anesthetics have excellent analgesic activity without inducing the side effect in the respiratory system. The aim and objective of the current experimental study was to access the neuroprotective effect of sevoflurane against isoflurane induced cognitive dysfunction in rats. Methods: Isoflurane was used for induction the neurodysfunction in the rats, and rats received the oral administration of sevoflurane (2.5, 5 and 10 mg/kg). Morris water test was carried out for the estimation of cognitive function. Neurochemical parameters, antioxidant parameters and pro-inflammatory cytokines were also estimated. Results: Sevoflurane significantly (P < 0.001) altered the neurochemical parameters such as anti-choline acetyltransferase, acetylcholine esterase, acetylcholine, protein carbonyl, choline brain-derived neurotrophic factor, and amyloid ß; antioxidant parameters such as glutathione, superoxide dismutase, and malondialdehyde; pro-inflammatory cytokines include interleukin (IL-2, IL-10, IL-4, IL-6, IL-10, IL-1ß), and tumor necrosis factor-α. Sevoflurane significantly reduced the activity of caspase-3. Conclusions: Sevoflurane exhibited the neuroprotection against the cognitive dysfunction in rats via anti-inflammatory and antioxidant mechanism.

Renal protective effect of ellipticine against streptozotocin induced diabetic nephropathy in rats via suppression of oxidative stress and inflammatory mediator

Purpose: Diabetes mellitus is a serious health problem worldwide, and diabetic nephropathy is the complication. The diabetic nephropathy considerably enhances the oxidative stress, glycation, lipid parameters and inflammatory reaction. Ellipticine has potent free radical scavenging and anti-inflammatory effect. Methods: In the current study, our objectives were to thoroughly examine the renal protective effects of ellipticine in a rat model of streptozotocin (STZ)-induced diabetic nephropathy (DN) and to elucidate the underlying mechanisms involved. For the induction of diabetic nephropathy, streptozotocin (50 mg/kg) was used, and rats were separated into groups and given varying doses of ellipticine (2.5, 5 and 7.5 mg/kg). The body weight, and renal weight were estimated. The inflammatory cytokines, renal biomarkers, inflammatory antioxidant, and urine parameters were estimated. Results: Result showed that ellipticine considerably enhanced the body weight and reduced the renal tissue weight. Ellipticine treatment significantly (P < 0.001) repressed the level of blood urea nitrogen, serum creatinine, uric acid, blood glucose and altered the lipid parameters. Ellipticine significantly (P < 0.001) repressed the level of malonaldehyde and boosted the glutathione, catalase, superoxide dismutase, and glutathione peroxidase. Ellipticine treatment significantly (P < 0.001) reduced the inflammatory cytokines and inflammatory mediators. Conclusions: Ellipticine could be a renal protective drug via attenuating the inflammatory reaction, fibrosis and oxidative stress in streptozotocin induced rats.

Correlation of fasting blood, salivary glucose and malondialdehyde in subjects with & without type 2 diabetes

Oxidative stress is identified as the common pathogenic factor that leads to insulin resistance in diabetics. Malondialdehyde is a product of lipid peroxidation. Aim: The aim of this study was to determine the variation in the Salivary malondialdehyde (MDA) among subjects with and without T2DM in comparison to the fasting blood and Salivary glucose. Methods: This study involved 29 healthy participants as Controls (group I) and 29 participants with Type 2 Diabetes Mellitus as Cases (group II). Salivary Glucose was analysed by glucose oxidase end-point assay. Thiobarbituric acid (TBA) assay method was considered for estimation of MDA in fasting saliva. Data was Statistically analysed using SPSS20. Parametric test was performed to analyse the data. Results: The correlation calculated between FBG with FSG level was found to be highly significant. A positive correlation between MDA levels with FBG was found. The relationship between FBG and FSG (r = 0.7815, p < 0.05), FBG and MDA (r =0.3678, p < 0.05) and FSG and MDA (r = 0.2869, p < 0.05) were found to be positively significant. Conclusion: Saliva as a unique body fluid can serve as a medium for biochemical analysis only in standard settings and with multiple measures to be used as a diagnostic tool in par with the gold standard serum. Salivary MDA levels can be considered as one of the oxidative stress markers in Type 2 Diabetic condition

Effects of Rooibos (Aspalathus linearis) on the Testicular Parenchyma of Adult BALB/C Mice Submitted to a Hypercaloric Diet

Oxidative stress due to obesity plays a detrimental role in the testicular microenvironment and sperm parameters. We explored the impact of a hypercaloric diet in male BALB/c mice as a condition to trigger damage to the spermatogenic process and the antioxidant effect of Aspalathus linearis as well. We used a hypercaloric diet in animals divided into 3 groups: Control, Hypercaloric diet control (HC) and Hypercaloric diet and Rooibos infusion (HCR). Morphometric parameters, enzyme dosages, cell viability, and tubular histopathology were evaluated. Body weight increased in HCR animals at weeks 3, 4, and 8. We found a reduction in seminiferous epithelium height, with an increase in the tubular diameter of the HCR group. Catalase levels were lower in HC and HCR, while carbonyl protein was decreased in HC. We estimate that it induces oxidative stress (OS) capable of affecting the seminiferous epithelium and that the infusion of A. linearis does not demonstrate a potential benefit in cell preservation.

Effect of a single resistance exercise session on inflammatory markers and oxidative stress in women living with HIV / Efeito de uma única sessão de exercício resistido sobre marcadores inflamatórios e estresse oxidativo em mulheres vivendo com hiv

ABSTRACT People living with HIV (PLH), who use antiretroviral therapy (ART), are more susceptible to changes in the inflammatory profile and oxidative stress, and women have greater access to ART. Although physical exercise is a complementary strategy to treatment due to its antioxidant and anti-inflammatory effects, it is not clear whether acute responses to exercise can be harmful to PLH. The aim of the study was to investigate the acute effect of resistance exercise (RE) on inflammatory and oxidative stress markers in PLH. Ten women, using ART, performed RE session consisting of seven exercises for the whole body. For biochemical evaluation, blood samples were collected before (pre), 1 hour (1h) and 2 hours (2h) after the RE session. One-way ANOVA followed by Bonferroni's post hoc test was used to compare results between time points. There was an increase only in markers, GSSG of 160% (pre: 0.40 ± 0.11; 1h: 1.18 ± 0.36; 2h: 1.04 ± 0.25 mmol/g), TNF-α of 98 % (pre: 4.60 ± 0.55; 1h: 6.95 ± 0.77; 2h: 9.10 ± 1.03 pg/ml) and 52% IL-6 (pre: 2.47 ± 0 .67; 1h: 3.63 ± 1.26; 2h: 5.38 ± 2.15 pg/ml). The other variables remained unchanged (P > 0.05). It is concluded that a RE session increased the levels of inflammatory markers and oxidative stress in PLH in a non-exacerbated way.

RESUMO Pessoas vivendo com HIV (PVH), que utilizam a terapia antirretroviral (TARV), são mais suscetíveis a alterações no perfil inflamatório e estresse oxidativo, sendo que as mulheres possuem maior acesso à TARV. Embora o exercício físico seja uma estratégia complementar ao tratamento devido aos seus efeitos antioxidantes e anti-inflamatórios, não está claro se as respostas agudas ao exercício podem ser prejudiciais às PVH. O objetivo do estudo foi investigar o efeito agudo de exercícios com pesos (EP) sobre marcadores inflamatórios e de estresse oxidativo em PVH. Dez mulheres, em uso da TARV, realizaram uma sessão de EP constituída por sete exercícios para o corpo todo. Para avaliação bioquímica, amostras de sangue foram coletadas antes (pré), 1 hora (1h) e 2 horas (2h) após a sessão de EP. A ANOVA one-way seguida do teste post hoc de Bonferroni foi utilizada para comparação dos resultados entre os momentos. Houve aumento apenas nos marcadores, GSSG de 160% (pré: 0,40 ± 0,11; 1h: 1,18 ± 0,36; 2h:1,04 ± 0,25 mmol/g), TNF-α de 98% (pré: 4,60 ± 0,55; 1h: 6,95 ± 0,77; 2h: 9,10 ± 1,03 pg/ml) e IL-6 de 52% (pré: 2,47 ± 0,67; 1h: 3,63 ± 1,26; 2h: 5,38 ± 2,15 pg/ml). As demais variáveis permaneceram sem alterações (P > 0,05). Conclui-se que uma sessão de EP aumentou os níveis de marcadores inflamatórios e estresse oxidativo em PVH de forma não exacerbada.