RESUMEN

Ischemic stroke occurs due a blockage in the blood flow to the brain, leading to damage to the nervous system. The prevalent morbidities resulting from stroke include post-stroke infection, as sepsis. Additionally, oxidative stress is recognized for inducing functional deficits in peripheral organs during sepsis. Therefore, sex differences in stroke exist and we aimed to investigate the peripheral oxidative stress caused by sepsis after stroke in male and female rats. Wistar rats (male and female) were divided into sham+sham, middle cerebral artery occlusion (MCAO) + sham, sham+ cecal ligation and perforation (CLP) and MCAO+CLP groups to males and female rats. Animals were subjected to MCAO or sham and after 7 days, were subjected to sepsis by CLP or sham. After 24 h, serum, total brain, lung, liver, heart, and spleen were collected. Brain edema, myeloperoxidase (MPO) activity, nitrite/nitrate (N/N) concentration, oxidative damage to lipids and proteins, and catalase activity were evaluated. Brain edema was observed only in male rats in MCAO+CLP group compared to MCAO+sham. Regarding MPO activity, an increase was verified in male in different organs and serum in MCAO+CLP group. For N/N levels, the increase was more pronounced in females submitted to MCAO+CLP. In general, to oxidative stress, an increase was only observed in animals exposed to MCAO+CLP, or with a greater increase in this group compared to the others. The findings provided the first indication that animals exposed to MCAO exhibit a heightened vulnerability to the harmful impacts of sepsis, as evidenced by brain edema and peripheral oxidative stress, and this susceptibility is dependent of sex.

Asunto(s)

Edema Encefálico , Modelos Animales de Enfermedad , Infarto de la Arteria Cerebral Media , Estrés Oxidativo , Peroxidasa , Ratas Wistar , Sepsis , Animales , Femenino , Masculino , Infarto de la Arteria Cerebral Media/metabolismo , Infarto de la Arteria Cerebral Media/patología , Infarto de la Arteria Cerebral Media/fisiopatología , Infarto de la Arteria Cerebral Media/sangre , Sepsis/metabolismo , Sepsis/fisiopatología , Sepsis/complicaciones , Sepsis/sangre , Factores Sexuales , Peroxidasa/metabolismo , Edema Encefálico/metabolismo , Edema Encefálico/patología , Edema Encefálico/fisiopatología , Nitratos/sangre , Nitratos/metabolismo , Nitritos/sangre , Nitritos/metabolismo , Ratas , Encéfalo/metabolismo , Encéfalo/patología , Encéfalo/irrigación sanguínea , Catalasa/metabolismo

RESUMEN

Chronic use of omeprazole has been linked to central effects alongside with the global concern of increasing appearance of neuropsychiatric disorders. This study aimed to identifying behavioral, inflammatory, and oxidative stress alterations after long-term administration of omeprazole. C57BL/6 mice were divided in groups: OME and Sham, each received either solutions of omeprazole or vehicle, administered for 28 days by gavage. Results observed in the omeprazole-treated mice: Decrease in the crossing parameter in the open field, no change in the motor performance assessed by rotarod, an immobility time reduction in the forced swimming test, improved percentage of correct alternances in the Ymaze and an exploration time of the novel object reduction in the novel object recognition. Furthermore, a reduced weight gain and hippocampal weight were observed. There was an increase in the cytokine IL1-ß levels in both prefrontal cortex (PFC) and serum, whereas TNF-α increased only in the PFC. Nitrite levels increased in the hippocampus (HP) and PFC, while malondialdehyde (MDA) and glutathione (GSH) levels decreased. These findings suggest that omeprazole improves depressive-like behavior and working memory, likely through the increase in nitrite and reduction in MDA levels in PFC and HP, whereas, the impairment of the recognition memory is more likely to be related to the reduced hippocampal weight. The diminished weight gain might be associated with the IL-1ß increased levels in the peripheral blood. Altogether, omeprazole showed to have the potential to impact at central level and inflammatory and oxidative parameters might exert a role between it.

Asunto(s)

Conducta Animal , Hipocampo , Ratones Endogámicos C57BL , Omeprazol , Estrés Oxidativo , Animales , Estrés Oxidativo/efectos de los fármacos , Omeprazol/farmacología , Omeprazol/administración & dosificación , Masculino , Conducta Animal/efectos de los fármacos , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Corteza Prefrontal/efectos de los fármacos , Corteza Prefrontal/metabolismo , Ratones , Glutatión/metabolismo , Malondialdehído/metabolismo , Interleucina-1beta/sangre , Interleucina-1beta/metabolismo , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Factor de Necrosis Tumoral alfa/sangre , Factor de Necrosis Tumoral alfa/metabolismo , Depresión/tratamiento farmacológico , Depresión/metabolismo , Inhibidores de la Bomba de Protones/farmacología , Inhibidores de la Bomba de Protones/administración & dosificación , Nitritos/sangre

RESUMEN

INTRODUCTION: Ingesting some foods can trigger headache attacks in migraine patients. Diet-sourced citrulline activates the l-arginine-nitric oxide pathway, acting on the pathophysiology of migraine. METHODS: The study was a clinical trial, interventional, controlled, and with group comparison. The sample was non-random, composed of 38 volunteers with migraine and 38 without headache (control). Both groups ingested a portion of watermelon to determine the onset of headache attacks. Before and after ingesting watermelon, they underwent blood collections to determine serum nitrite levels. RESULTS: There were 38 volunteers diagnosed with migraine without aura and 38 controls, whose mean age was, respectively, 22.4 ± 1.5 and 22.9 ± 3.1 years (p = 0.791). Headache was triggered by watermelon ingestion after 124.3 ± 20.5 min of ingestion in 23.7% (9/38) of the migraine volunteers and in none of the controls (p = 0.002). There was an increase in serum nitrite levels, both in migraine volunteers (23.4%) and in the control group (24.3%), after watermelon ingestion. This difference was significant (p < 0.001). DISCUSSION: Watermelon ingestion triggered headache attacks in migraine patients and increased serum nitrite levels, attesting to a possible activation of the l-arginine-nitric oxide pathway.

Asunto(s)

Citrullus , Trastornos Migrañosos , Adulto , Humanos , Adulto Joven , Arginina , Citrullus/efectos adversos , Ingestión de Alimentos , Cefalea/etiología , Trastornos Migrañosos/etiología , Óxido Nítrico , Nitritos/sangre

RESUMEN

Nitric oxide (NO) metabolites have physiological and pharmacological importance and increasing their tissue concentrations may result in beneficial effects. Tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl) has antioxidant properties that may improve NO bioavailability. Moreover, tempol increases oral nitrite-derived gastric formation of S-nitrosothiols (RSNO). We hypothesized that pretreatment with tempol may further increase tissue concentrations of NO-related species after oral nitrite administration and therefore we carried out a time-dependent analysis of how tempol affects the concentrations of NO metabolites in different tissues after oral nitrite administration to rats. NO metabolites (nitrate, nitrite and RSNO) were assessed by ozone-based reductive chemiluminescence assays in plasma, stomach, aorta, heart and liver samples obtained from anesthetized rats at baseline conditions and 15 min, 30 min, 2 h or 24 h after oral nitrite (15 mg/kg) was administered to rats pretreated with tempol (18 mg/kg) or vehicle 15 min prior to nitrite administration. Aortic protein nitrosation was assessed by resin-assited capture (SNO-RAC) method. We found that pretreatment with tempol transiently enhanced nitrite-induced increases in nitrite, RSNO and nitrate concentrations in the stomach and in the plasma (all P < 0.05), particularly for 15-30 min, without affecting aortic protein nitrosation. Pretreatment with tempol enhanced nitrite-induced increases in nitrite (but not RSNO or nitrate) concentrations in the heart (P < 0.05). In contrast, tempol attenuated nitrite-induced increases in nitrite, RSNO or nitrate concentrations in the liver. These findings show that pretreatment with tempol affects oral nitrite-induced changes in tissue concentrations of NO metabolites depending on tissue type and does not increase nitrite-induced vascular nitrosation. These results may indicate that oral nitrite therapy aiming at achieving increased nitrosation of cardiovascular targets requires appropriate doses of nitrite and is not optimized by tempol.

Asunto(s)

Antioxidantes/farmacología , Óxidos N-Cíclicos/farmacología , Óxido Nítrico/metabolismo , Nitritos/administración & dosificación , Administración Oral , Animales , Masculino , Nitratos/sangre , Nitritos/sangre , Ratas , Ratas Wistar , Marcadores de Spin

RESUMEN

BACKGROUND AND AIMS: Preeclampsia is associated with reduced nitric oxide (NO) bioavailability. Arginase is related to NO synthesis, but relatively unexplored in preeclampsia. However, no previous study has examined whether variations in ARG1 and ARG2 genes affect NO bioavailability and the risk of preeclampsia. Here, we compared the alleles and genotypes of single nucleotide polymorphisms (SNPs) in ARG1 (rs2781659; rs2781667; rs2246012; rs17599586) and ARG2 (rs3742879; rs10483801) in healthy pregnant women and preeclampsia, and examined whether these SNPs affect plasma nitrite concentrations (a marker of NO formation) in these groups. METHODS: Genotypes for the ARG1 and ARG2 SNPs were determined by Taqman probe and plasma nitrite by an ozone-based chemiluminescence assay. RESULTS: Regarding ARG1 SNPs, the GG genotype and G allele frequencies for rs2781659, and the C allele frequencies for rs2246012 were higher in preeclampsia compared to healthy pregnant women. Moreover, the GG genotype for rs2781659 and the TT genotype for rs2781667 were associated with higher plasma nitrite in healthy pregnant. We found no association of ARG2 polymorphisms with preeclampsia or nitrite levels in the study groups. CONCLUSIONS: Our results suggest that SNPs of ARG1 increase the risk of preeclampsia and modulate plasma nitrite levels in healthy pregnant women.

Asunto(s)

Arginasa/genética , Óxido Nítrico/metabolismo , Preeclampsia/genética , Embarazo/genética , Adulto , Femenino , Frecuencia de los Genes , Humanos , Óxido Nítrico/sangre , Nitritos/sangre , Nitritos/metabolismo , Polimorfismo de Nucleótido Simple , Preeclampsia/sangre , Preeclampsia/metabolismo , Adulto Joven

RESUMEN

PURPOSE: Propofol anesthesia is usually accompanied by hypotensive responses, which are at least in part mediated by nitric oxide (NO). Arginase I (ARG1) and arginase II (ARG2) compete with NO synthases for their common substrate L-arginine, therefore influencing the NO formation. We examined here whether ARG1 and ARG2 genotypes and haplotypes affect the changes in blood pressure and NO bioavailability in response to propofol. METHODS: Venous blood samples were collected from 167 patients at baseline and after 10 min of anesthesia with propofol. Genotypes were determined by polymerase chain reaction. Nitrite concentrations were measured by using an ozone-based chemiluminescence assay, while NOx (nitrites + nitrates) levels were determined by using the Griess reaction. RESULTS: We found that patients carrying the AG + GG genotypes for the rs3742879 polymorphism in ARG2 gene and the ARG2 GC haplotype show lower increases in nitrite levels and lower decreases in blood pressure after propofol anesthesia. On the other hand, subjects carrying the variant genotypes for the rs10483801 polymorphism in ARG2 gene show more intense decreases in blood pressure (CA genotype) and/or higher increases in nitrite levels (CA and AA genotypes) in response to propofol. CONCLUSION: Our results suggest that ARG2 variants affect the hypotensive responses to propofol, possibly by modifying NO bioavailability. TRIAL REGISTRATION: NCT02442232.

Asunto(s)

Anestésicos Intravenosos/efectos adversos , Arginasa/genética , Hipotensión/inducido químicamente , Óxido Nítrico/metabolismo , Propofol/efectos adversos , Adulto , Anciano , Anestésicos Intravenosos/farmacocinética , Femenino , Genotipo , Haplotipos , Humanos , Masculino , Persona de Mediana Edad , Nitratos/sangre , Nitritos/sangre , Reacción en Cadena de la Polimerasa , Polimorfismo de Nucleótido Simple , Propofol/farmacocinética

RESUMEN

OBJECTIVE: Investigate the effects of photobiomodulation (PBM) on the expression of IL-10 and nitrites in individuals with Relapsing-Remitting multiple sclerosis (MS), as these biomarkers play a fundamental role in the physiopathology of the disease. The modulation of IL-10 and nitrites through treatment with PBM may be a novel treatment modality for MS. METHODS: A randomized, uncontrolled, clinical trial was conducted involving 14 individuals with a diagnosis of Relapsing-Remitting MS and a score of up to 6.0 on the Expanded Disability Status Scale (EDSS). THE PARTICIPANTS WERE RANDOMIZED TO TWO GROUPS: Group 1 -PBM in the sublingual region; Group 2 -PBM over the radial artery. Irradiation was administered with a wavelength of 808 nm and output power of 100 mW for 360 seconds twice a week, totaling 24 sessions. Peripheral blood was analyzed for the determination of serum levels of IL-10 and nitrites. RESULTS: After treatment with PBM, the expression of IL-10 increased in both the sublingual group (pre-treatment: 2.8 ± 1.4 pg/ml; post-treatment: 8.3 ± 2.4 pg/ml) and the radial artery group (pre-treatment: 2.7 pg/ml ± 1.4; post-treatment: 11.7 ± 3.8 pg/ml). In contrast, nitrite levels were not modulated in the sublingual group (pre-treatment: 65 ± 50 nmol/mg protein; post-treatment: 51 ± 42 nmol/mg protein) or the radial artery group (pre-treatment: 51 ± 16 nmol/mg protein; post-treatment: 42 ± 7 nmol/mg protein). CONCLUSION: Treatment with PBM positively modulated the expression of IL-10 but had no effect on nitrite levels. Further studies should be conducted with a larger sample and a control group, as PBM may be a promising complementary treatment for the management of MS. This trial is registered at ClinicalTrials.gov. Identifier: NCT03360487.

Asunto(s)

Interleucina-10/metabolismo , Terapia por Luz de Baja Intensidad , Esclerosis Múltiple Recurrente-Remitente/radioterapia , Nitritos/metabolismo , Adulto , Femenino , Humanos , Láseres de Semiconductores/uso terapéutico , Masculino , Persona de Mediana Edad , Esclerosis Múltiple Recurrente-Remitente/patología , Nitritos/sangre , Modalidades de Fisioterapia , Arteria Radial/metabolismo , Arteria Radial/efectos de la radiación , Adulto Joven

RESUMEN

Proton pump inhibitors (PPI) are suppressors of gastric acid secretion (SGAS) that decrease gastric nitric oxide (NO) formation from nitrite and increase the cardiovascular risk. However, H2 receptor antagonists (H2RA) are considered safer than PPIs. We challenged this notion and hypothesized that both omeprazole (PPI) and ranitidine (H2RA) attenuate the responses to oral nitrite because both drugs increase gastric pH and therefore could decrease nitrite-derived NO formation in the stomach. We examined the blood pressure responses to oral nitrite in hypertensive rats treated with omeprazole, ranitidine, or vehicle. Chemiluminensce-based assays were used to measure gastric NO formation, plasma and gastric concentrations of nitrite, nitrate, and nitrosylated species (RXNO) to clarify the mechanism involved in the effects of SGAS on the responses to oral nitrite. Both drugs increased gastric pH, impaired oral nitrite-induced hypotensive responses, gastric NO formation, and blunted the increases in circulating RXNO concentrations, but not in circulating nitrite and nitrate concentrations. These findings were reproduced in a second study using sodium acetate buffers at pH 3.5, 4.5, and 5.5 to mimic gastric pH found with vehicle, ranitidine, and omeprazole, respectively. Increasing gastric pH impaired oral nitrite-induced hypotensive responses, gastric NO formation, and blunted the increases in circulating RXNO concentrations, but not in circulating nitrite and nitrate concentrations. Our results clearly indicate that SGAS impair nitrite-induced gastric formation of NO and vasoactive RXNO in a pH-dependent manner, thus resulting in impaired responses to oral nitrite. These findings may have several clinical implications, particularly to patients with cardiovascular diseases.

Asunto(s)

Antihipertensivos/administración & dosificación , Ácido Gástrico/química , Ácido Gástrico/metabolismo , Antagonistas de los Receptores H2 de la Histamina/administración & dosificación , Hipertensión/tratamiento farmacológico , Omeprazol/administración & dosificación , Inhibidores de la Bomba de Protones/administración & dosificación , Ranitidina/administración & dosificación , Nitrito de Sodio/administración & dosificación , Administración Oral , Animales , Presión Sanguínea/efectos de los fármacos , Modelos Animales de Enfermedad , Mucosa Gástrica/metabolismo , Concentración de Iones de Hidrógeno/efectos de los fármacos , Masculino , Nitratos/análisis , Nitratos/sangre , Óxido Nítrico/análisis , Óxido Nítrico/metabolismo , Nitritos/análisis , Nitritos/sangre , Ratas , Ratas Wistar , Resultado del Tratamiento

RESUMEN

BACKGROUND & PURPOSE: It is well established that end-stage renal disease (ESRD) is associated with increased cardiovascular morbidity and mortality both in the adult and pediatric population. Although the underlying molecular mechanisms are poorly understood, compromised nitric oxide (NO) bioactivity has been suggested as a contributing factor. With this in mind, we investigated the effects of hemodialysis on NO homeostasis and bioactivity in blood. METHODS & RESULTS: Plasma and dialysate samples were obtained before and after hemodialysis sessions from adults (n = 33) and pediatric patients (n = 10) with ESRD on chronic renal replacement therapy, and from critically ill adults with acute kidney injury (n = 12) at their first sustained low-efficiency dialysis session. Levels of nitrate, nitrite, cyclic guanosine monophosphate (cGMP) and amino acids relevant for NO homeostasis were analyzed. We consistently found that nitrate and cGMP levels in plasma were significantly reduced after hemodialysis, whereas post-dialysis nitrite and amino acids coupled to NO synthase activity (i.e., arginine and citrulline) were only significantly reduced in adults with ESRD. The amount of excreted nitrate and nitrite during dialysis were similar to daily endogenous levels that would be expected from endothelial NO synthase activity. CONCLUSIONS: Our results show that hemodialysis significantly reduces circulating levels of nitrate and cGMP, indicating that this medical procedure may impair NO synthesis and potentially NO signaling pathways.

Asunto(s)

Lesión Renal Aguda/terapia , Fallo Renal Crónico/terapia , Nitratos/aislamiento & purificación , Nitritos/aislamiento & purificación , Diálisis Renal , Lesión Renal Aguda/sangre , Adulto , Niño , Estudios Transversales , Femenino , Humanos , Fallo Renal Crónico/sangre , Masculino , Nitratos/sangre , Nitritos/sangre , Estudios Prospectivos

RESUMEN

The cyclitol bornesitol is the main constituent of the leaves from the antihypertensive medicinal plant Hancornia speciosa. This study aimed to investigate the ability of bornesitol to reduce blood pressure and its mechanism of action. Normotensive Wistar rats were divided into control group and bornesitol groups treated intravenously with bornesitol (0.1, 1.0 and 3.0 mg/kg). Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were recorded in non-anesthetized awake animals. Nitric oxide (NO) and angiotensin-converting enzyme (ACE) were measured in plasma by using colorimetric methods. Vascular reactivity study was performed in rat aorta rings and the involvement of nitric oxide synthase (NOS), calcium-calmodulin complex and phosphatidylinositol-3-kinase (PI3K)/Akt pathway in the vasodilator effect was investigated. Administration of bornesitol significantly reduced the SBP, increased the plasmatic level of nitrite, and decreased ACE activity in normotensive rats. In the rat aorta, bornesitol induced endothelium-dependent vasodilatation, which was abolished by NOS blockade. While calcium-calmodulin complex inhibition decreased the vasodilator effect of bornesitol, the inhibition of PI3K/Akt pathway did not alter it. Bornesitol reduced the blood pressure by a mechanism involving an increased production or bioavailability of NO, inhibition of ACE, and by an endothelium- and NO-dependent vasodilator effect. The present results support the use of bornesitol as an active marker for the cardiovascular activity of Hancornia speciosa.

Asunto(s)

Antihipertensivos/farmacología , Apocynaceae , Ciclitoles/farmacología , Vasodilatadores/farmacología , Animales , Aorta Torácica/efectos de los fármacos , Aorta Torácica/fisiología , Presión Sanguínea/efectos de los fármacos , Brasil , Masculino , Óxido Nítrico/sangre , Nitritos/sangre , Peptidil-Dipeptidasa A/sangre , Hojas de la Planta , Plantas Medicinales , Ratas Wistar

RESUMEN

Stroke survivors are at substantial risk of recurrent cerebrovascular event or cardiovascular disease. Exercise training offers nonpharmacological treatment for these subjects; however, the execution of the traditional exercise protocols and adherence is constantly pointed out as obstacles. Based on these premises, the present study investigated the impact of an 8-week dynamic resistance training protocol with elastic bands on functional, hemodynamic, and cardiac autonomic modulation, oxidative stress markers, and plasma nitrite concentration in stroke survivors. Twenty-two patients with stroke were randomized into control group (CG, n = 11) or training group (TG, n = 11). Cardiac autonomic modulation, oxidative stress markers, plasma nitrite concentration, physical function and hemodynamic parameters were evaluated before and after 8 weeks. Results indicated that functional parameters (standing up from the sitting position (P = 0.011) and timed up and go (P = 0.042)) were significantly improved in TG. Although not statistically different, both systolic blood pressure (Δ = -10.41 mmHg) and diastolic blood pressure (Δ = -8.16 mmHg) were reduced in TG when compared to CG. Additionally, cardiac autonomic modulation (sympathovagal balance-LF/HF ratio) and superoxide dismutase were improved, while thiobarbituric acid reactive substances and carbonyl levels were reduced in TG when compared to the CG subjects. In conclusion, our findings support the hypothesis that dynamic resistance training with elastic bands may improve physical function, hemodynamic parameters, autonomic modulation, and oxidative stress markers in stroke survivors. These positive changes would be associated with a reduced risk of a recurrent stroke or cardiac event in these subjects.

Asunto(s)

Estrés Oxidativo , Entrenamiento de Fuerza , Rehabilitación de Accidente Cerebrovascular/métodos , Accidente Cerebrovascular/patología , Anciano , Presión Sanguínea , Enfermedad Crónica , Femenino , Fuerza de la Mano , Hemodinámica , Humanos , Masculino , Persona de Mediana Edad , NADPH Oxidasas/metabolismo , Nitritos/sangre , Carbonilación Proteica , Accidente Cerebrovascular/metabolismo , Superóxido Dismutasa/metabolismo , Sobrevivientes

RESUMEN

Diabetic foot ulcer is one of the most frightened diabetic complications leading to amputation disability and early mortality. Diabetic wounds exhibit a complex networking of inflammatory cytokines, local proteases, and reactive oxygen and nitrogen species as a pathogenic polymicrobial biofilm, overall contributing to wound chronification and host homeostasis imbalance. Intralesional infiltration of epidermal growth factor (EGF) has emerged as a therapeutic alternative to diabetic wound healing, reaching responsive cells while avoiding the deleterious effect of proteases and the biofilm on the wound's surface. The present study shows that intralesional therapy with EGF is associated with the systemic attenuation of pro-inflammatory markers along with redox balance recovery. A total of 11 diabetic patients with neuropathic foot ulcers were studied before and 3 weeks after starting EGF treatment. Evaluations comprised plasma levels of pro-inflammatory, redox balance, and glycation markers. Pro-inflammatory markers such as erythrosedimentation rate, C-reactive protein, interleukin-6, soluble FAS, and macrophage inflammatory protein 1-alpha were significantly reduced by EGF therapy. Oxidative capacity, nitrite/nitrate ratio, and pentosidine were also reduced, while soluble receptor for advanced glycation end-products significantly increased. Overall, our results indicate that the local intralesional infiltration of EGF translates in systemic anti-inflammatory and antioxidant effects, as in attenuation of the glycation products' negative effects.

Asunto(s)

Pie Diabético/tratamiento farmacológico , Factor de Crecimiento Epidérmico/uso terapéutico , Proteínas Recombinantes/uso terapéutico , Anciano , Arginina/análogos & derivados , Arginina/sangre , Biomarcadores/sangre , Sedimentación Sanguínea , Proteína C-Reactiva/análisis , Quimiocina CCL3/sangre , Citocinas/sangre , Femenino , Humanos , Inyecciones Intralesiones , Lisina/análogos & derivados , Lisina/sangre , Masculino , Persona de Mediana Edad , Nitratos/sangre , Nitritos/sangre , Receptor para Productos Finales de Glicación Avanzada/sangre , Cicatrización de Heridas , Receptor fas/sangre

RESUMEN

Oxidative stress and inflammation are the key players in the development of motor dysfunction post-spinal cord ischemic reperfusion injury (SC-IRI). This study investigated the protective effect of concomitant pre-administration of melatonin and alpha-tocopherol on the early complications (after 48 hours) of spinal cord IRI injury in rats. Melatonin or α-tocopherol were preadministered either individually or in combination for 2 weeks, then rats were exposed SC-IRI. Neurological examinations of the hind limbs and various biochemical markers of oxidative stress and inflammation in the SC tissue were assessed. Solely pre-administration of either melanin or α-tocopherol significantly but partially improved motor and sensory function of the hind limbs mediated by partial decreases in SC levels of MDA, AOPP and PGE2 levels and activities of SOD, partial significant decreases in plasma levels of total nitrate/nitrite and significant increases in AC activity of GSH-Px. However, combination therapy of both drugs resulted in the maximum improvements in all neurological assessments tested and biochemical endpoints. In conclusion, by their synergistic antioxidant and antiinflammatory actions, the combination therapy of melatonin and α-tocopherol alleviates SC-IRI induced paraplegia.

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El estrés oxidativo y la inflamación son claves en el desarrollo de la disfunción motora posterior a lesión isquémica de la médula espinal (SC-IRI). Este estudio investigó acerca del efecto protector de la administración previa concomitante de la melatonina y alfa-tocoferol en las complicaciones tempranas (después de 48 horas) de la lesión de IRI de la médula espinal en ratas. La melatonina o el α-tocoferol se administraron individualmente o en combinación durante 2 semanas, luego las ratas fueron expuestas a SC-IRI. Se evaluaron los exámenes neurológicos de las miembros pélvicos y diversos marcadores bioquímicos de estrés oxidativo e inflamación en el tejido subcutáneo. Solo la administración previa de melatonina o α-tocoferol mejoró parcial y significativamente la función motora y sensorial de los miembros pélvicos mediadas por disminuciones parciales en los niveles de SC de los niveles de MDA, AOPP y PGE2 y las actividades de la SOD, disminuciones significativas parciales en los niveles plasmáticos del total nitrato / nitrito y aumentos significativos en la actividad de AC de GSH-Px. Sin embargo, se observaron los mejores resultados durante la combinación de ambos fármacos en todas las evaluaciones neurológicas y en los puntos finales bioquímicos. En conclusión, debido a sus acciones antioxidantes y antiinflamatorias sinérgicas, la terapia de melatonina y α-tocoferol alivia la paraplejía inducida por SC-IRI.

Asunto(s)

Animales , Ratas , Daño por Reperfusión/tratamiento farmacológico , Isquemia de la Médula Espinal/tratamiento farmacológico , Melatonina/administración & dosificación , Antioxidantes/administración & dosificación , Paraplejía , Médula Espinal/efectos de los fármacos , Médula Espinal/patología , Dinoprostona/sangre , Ratas Sprague-Dawley , Estrés Oxidativo/efectos de los fármacos , Tocoferoles/farmacología , Melatonina/farmacología , Nitritos/sangre , Antioxidantes/farmacología

RESUMEN

The effects of circadian misalignment and work shift on oxidative stress profile of shift workers have not been explored in the literature. The present study aimed to evaluate the role of shift work (day and night) and social jetlag - a measure of circadian misalignment - with oxidative stress markers. A cross-sectional study was performed with 79 men (21-65 years old, 27.56 ± 4.0 kg/m2) who worked the night shift (n = 37) or daytime (n = 42). The analyzed variables included anthropometric measures and determination of systemic levels of markers of oxidative damage and antioxidant defense. Social jetlag was calculated by the absolute difference between the mean sleep point on working and rest days. The night group presented higher systemic values of thiobarbituric acid reactive substances and hydrogen peroxide, and lower levels of nitrite, total antioxidant capacity, and catalase and superoxide dismutase activities in relation to the day group. However, social jetlag was not associated with oxidative stress-related biomarkers analyzed in the night group. These results suggest that the night worker has higher levels of oxidative stress damage and lower levels of antioxidant defenses, while social jetlag was not a possible responsible factor for this condition.

Asunto(s)

Antioxidantes/metabolismo , Horario de Trabajo por Turnos , Sueño , Tolerancia al Trabajo Programado/fisiología , Adulto , Anciano , Biomarcadores/sangre , Proteínas Sanguíneas/metabolismo , Índice de Masa Corporal , Estudios Transversales , Enzimas/sangre , Humanos , Síndrome Jet Lag , Persona de Mediana Edad , Nitritos/sangre , Oxidación-Reducción , Estrés Oxidativo , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismo , Adulto Joven

RESUMEN

This study aimed to verify the effect of beetroot juice on post-exercise ambulatory blood pressure (BP) in obese individuals. Fourteen non-hypertensive obese males were randomly assigned to three experimental sessions: 1) Beetroot juice with exercise (BJE, 200ml with ≈ 800mg nitrate and 40 minutes of moderate-intensity aerobic exercise at an intensity of 50% of the heart rate reserve), 2) fruit soda with exercise (FSE, 200ml of a low-nitrate drink and the same exercise session) and 3) control (CON, 200ml of water, an insignificant nitrate drink without exercise). The concentration of total nitrites and nitrates in plasma (NOx) after the drinks and the 24-hour ambulatory BP were evaluated. A two-way (condition vs. time) ANOVA for repeated measures, with a Bonferroni post hoc was used to analyze variables. The plasma NOx concentration increased significantly after ingestion of beetroot juice (from 9.9 ± 8.4 µM to 47.0 ± 16.9 µM, p < 0.001) and remained elevated until 1 hour post-intervention (54.7 ± 10.1 µM, p < 0.001), while it did not change in FSE and CON groups. The BJE session decreased ambulatory systolic BP in 5.3 mmHg (IC95%, -10.1 to -0.6, p = 0.025) in the period of 1-6 h after the BJE session compared to the CON session and reduction of 3.8 mmHg (IC95%, -7.5 to -0.007, p = 0.05) compared to the FSE session. No significant changes were observed for ambulatory diastolic BP (p > 0.05). BJE enhanced the reduction of systolic ambulatory BP up to 6 hours following a moderate-intensity aerobic exercise in obese individuals with an elevated cardiovascular risk profile.

Asunto(s)

Presión Sanguínea/efectos de los fármacos , Suplementos Dietéticos , Ejercicio Físico/fisiología , Nitratos/administración & dosificación , Obesidad/fisiopatología , Adulto , Antropometría , Beta vulgaris/química , Enfermedades Cardiovasculares , Estudios Cruzados , Humanos , Masculino , Nitratos/sangre , Nitritos/sangre , Obesidad/sangre , Estudios Prospectivos , Factores de Riesgo , Adulto Joven

RESUMEN

l-Arginine supplementation is a potential therapy for treating cardiovascular and metabolic diseases. However, the use of distinct l-arginine sources, intervened populations, and treatment regimens may have yielded confusion about their efficacy. This research constitutes a systematic review and meta-analysis summarizing the effects of l-arginine supplementation compared to placebo in individuals with cardiovascular disease (CVD), obesity, or diabetes. Eligibility criteria included randomized clinical trials and interventions based on oral supplementation of l-arginine with a minimum duration of three days; comparison groups consisted of individuals with the same disease condition receiving an oral placebo substance. The primary outcome was flow-mediated dilation, and secondary outcomes were nitrite/nitrate (NOx) rate and asymmetric dimethylarginine (ADMA). Statistical heterogeneity among studies included in the meta-analyses was assessed using the inconsistency index (I2). Fifty-four full-text articles from 3761 retrieved references were assessed for eligibility. After exclusions, 13 studies were included for data extraction. There was no difference in blood flow after post-ischemic hyperemia between the supplementation of l-arginine and placebo groups before and after the intervention period (standardized mean difference (SMD) = 0.30; 95% confidence intervals (CIs) = -0.85 to 1.46; I2 = 96%). Sensitivity analysis showed decreased heterogeneity when the studies that most favor arginine and placebo were removed, and positive results in favor of arginine supplementation were found (SMD = 0.59; 95% CIs = 0.10 to 1.08; I2 = 75%). No difference was found in meta-analytical estimates of NOx and ADMA responses between arginine or placebo treatments. Overall, the results indicated that oral l-arginine supplementation was not associated with improvements on selected variables in these patients (PROSPERO Registration: CRD42017077289).

Asunto(s)

Arginina/administración & dosificación , Enfermedades Cardiovasculares/terapia , Diabetes Mellitus/terapia , Suplementos Dietéticos , Endotelio Vascular , Obesidad/terapia , Adulto , Anciano , Arginina/análogos & derivados , Arginina/sangre , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/complicaciones , Diabetes Mellitus/sangre , Diabetes Mellitus/fisiopatología , Endotelio Vascular/fisiopatología , Femenino , Humanos , Hiperemia/etiología , Masculino , Persona de Mediana Edad , Nitratos/sangre , Nitritos/sangre , Obesidad/sangre , Obesidad/fisiopatología , Resultado del Tratamiento

RESUMEN

Endothelial nitric oxide synthase (eNOS) gene polymorphisms are associated with reduced eNOS activity and nitric oxide (NO) production leading to an increase in blood pressure (BP). Regular exercise is the main strategy to minimize the deleterious effects of polymorphisms. However, due to the differences that physical exercise can be performed, some controversial results are found. Therefore it seems reasonable to evaluate the training status (TS). Thus, this study aimed to investigate the association of eNOS gene haplotypes and different levels of TS on nitrite concentrations (NO2-) and BP values in older adult. 424 elderly performed the following assessments: General Functional Fitness Index (GFFI) to estimate TS, systolic and diastolic blood pressure (SBP and DBP), blood collection for analysis of NO2- and g.-786T>C, intron 4b/a (VNTR) and 894G>T polymorphisms. Multivariate logistic regression showed that NO2- was influenced by GFFI and 4b/4a Intron 4. Regarding BP, GFFI influenced SBP and DBP, and just intron 4 was associated with variations in DBP. It can be observed that GFFI affected the NO2-, SBP and DBP independently of haplotypes. Therefore, maintenance of good level of TS can overcome the negative influence of genetics factors (intron 4) by increasing NO2- concentration and decreasing BP values.

Asunto(s)

Presión Sanguínea/fisiología , Óxido Nítrico Sintasa de Tipo III/genética , Nitritos/sangre , Aptitud Física , Anciano , Ejercicio Físico , Femenino , Genotipo , Haplotipos , Humanos , Intrones , Modelos Logísticos , Masculino , Persona de Mediana Edad , Polimorfismo Genético

RESUMEN

Physical exercise induces inflammatory and oxidative markers production in the skeletal muscle and this process is under the control of both endogenous and exogenous modulators. Recently, molecular hydrogen (H2) has been described as a therapeutic gas able to reduced oxidative stress in a number of conditions. However, nothing is known about its putative role in the inflammatory and oxidative status during a session of acute physical exercise in sedentary rats. Therefore, we tested the hypothesis that H2 attenuates both inflammation and oxidative stress induced by acute physical exercise. Rats ran at 80% of their maximum running velocity on a closed treadmill inhaling either the H2 gas (2% H2, 21% O2, balanced with N2) or the control gas (0% H2, 21% O2, balanced with N2) and were euthanized immediately or 3 h after exercise. We assessed plasma levels of inflammatory cytokines [tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß and IL-6] and oxidative markers [superoxide dismutase (SOD), thiobarbituric acid reactive species (TBARS) and nitrite/nitrate (NOx)]. In addition, we evaluated the phosphorylation status of intracellular signaling proteins [glycogen synthase kinase type 3 (GSK3α/ß) and the cAMP responsive element binding protein (CREB)] that modulate several processes in the skeletal muscle during exercise, including changes in exercise-induced reactive oxygen species (ROS) production. As expected, physical exercise increased virtually all the analyzed parameters. In the running rats, H2 blunted exercise-induced plasma inflammatory cytokines (TNF-α and IL-6) surges. Regarding the oxidative stress markers, H2 caused further increases in exercise-induced SOD activity and attenuated the exercise-induced increases in TBARS 3 h after exercise. Moreover, GSK3α/ß phosphorylation was not affected by exercise or H2 inhalation. Otherwise, exercise caused an increased CREB phosphorylation which was attenuated by H2. These data are consistent with the notion that H2 plays a key role in decreasing exercise-induced inflammation, oxidative stress, and cellular stress.

Asunto(s)

Antiinflamatorios/farmacología , Antioxidantes/farmacología , Hidrógeno/farmacología , Músculo Esquelético/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Especies Reactivas de Oxígeno/antagonistas & inhibidores , Administración por Inhalación , Animales , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/sangre , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/genética , Glucógeno Sintasa Quinasa 3 beta/sangre , Glucógeno Sintasa Quinasa 3 beta/genética , Interleucina-1beta/antagonistas & inhibidores , Interleucina-1beta/sangre , Interleucina-1beta/genética , Interleucina-6/antagonistas & inhibidores , Interleucina-6/sangre , Interleucina-6/genética , Isoenzimas/sangre , Isoenzimas/genética , Masculino , Músculo Esquelético/metabolismo , Músculo Esquelético/fisiopatología , Nitratos/antagonistas & inhibidores , Nitratos/sangre , Nitritos/antagonistas & inhibidores , Nitritos/sangre , Condicionamiento Físico Animal/métodos , Esfuerzo Físico/efectos de los fármacos , Ratas , Ratas Wistar , Especies Reactivas de Oxígeno/sangre , Carrera , Superóxido Dismutasa/sangre , Superóxido Dismutasa/genética , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismo , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Factor de Necrosis Tumoral alfa/sangre , Factor de Necrosis Tumoral alfa/genética

RESUMEN

Propofol anesthesia is usually accompanied by hypotension, which is at least in part related to enhanced endothelial nitric oxide synthase (NOS3)-derived NO bioavailability. We examined here whether NOS3 polymorphisms (rs2070744, 4b/4a VNTR, rs3918226 and rs1799983) and haplotypes affect the changes in blood pressure and NO bioavailability induced by propofol. Venous blood samples were collected from 168 patients at baseline and after 10 min of anesthesia with propofol 2 mg/kg administered intravenously by bolus injection. Genotypes were determined by polymerase chain reaction and haplotype frequencies were estimated. Nitrite concentrations were measured by using an ozone-based chemiluminescence assay, while NOx (nitrites + nitrates) levels were determined by using the Griess reaction. We found that CT + TT genotypes for the rs3918226 polymorphism, the ba + aa genotypes for the 4b/4a VNTR and the CTbT haplotype were associated with lower decreases in blood pressure and lower increases in nitrite levels after propofol anesthesia. On the other hand, the TCbT and CCbT haplotypes were associated with more intense decreases in blood pressure and higher increases in nitrite levels in response to propofol. Our results suggest that NOS3 polymorphisms and haplotypes influence the hypotensive responses to propofol, possibly by affecting NO bioavailability.

Asunto(s)

Presión Sanguínea/genética , Óxido Nítrico Sintasa de Tipo III/genética , Óxido Nítrico/farmacocinética , Polimorfismo de Nucleótido Simple , Propofol/farmacología , Adulto , Anciano , Anestésicos Intravenosos/farmacología , Disponibilidad Biológica , Presión Sanguínea/efectos de los fármacos , Haplotipos , Humanos , Masculino , Persona de Mediana Edad , Nitratos/sangre , Nitritos/sangre

RESUMEN

Moraga, Fernando A., Giselle Miranda, Vasthi López, Carmen Vallejos, and Daniel Silva. Chronic intermittent hypobaric hypoxia (4600 M) attenuates pulmonary vasodilation induced by acetylcholine or sodium nitroprusside. High Alt Med Biol. 19:149-155, 2018. BACKGROUND: Previous studies performed in rats exposed to chronic intermittent hypobaric hypoxia (CIHH), at a simulated altitude of 4600 m, showed reduced nitric oxide (NO) production, increased arginase activity, and increased oxidative stress. However, studies on vascular function are scarce. Our aim was to measure plasma nitrate and nitrite (NOx) concentration and study pulmonary vascular function in rats exposed to CIHH in the presence of potassium chloride (KCl), acetylcholine (Ach), and sodium nitroprusside (SNP). METHODS: Thirty male Wistar rats were divided into two groups: A control group (normoxia (N), n = 10) and a CIHH group (2N × 2H × 30 days, n = 20). CIHH exposure was performed in a hypobaric chamber at 428 Torr (4600 m). Noninvasive systolic blood pressure (SBP), heart rate, and body weight (BW) were measured. Blood samples were obtained to measure NOx levels and hematocrit (Hct). CIHH animals that gained BW and presented a Hct <20% and maintained SBP were classified as tolerant, and animals that lost >30% of their BW, increased Hct and SBP >20% were classified as intolerant. Animals were sacrificed and small pulmonary arteries (SPA) were obtained to perform concentration-response curves to KCl, Ach, and SNP. RESULTS AND CONCLUSIONS: Intolerant rats (30%) had decreased NOx levels. SPA had a larger vasocontraction response to KCl and a lower dilation response to SNP in the SPA compared to tolerant and control animals. In addition, SPA had a lower dilatation response to Ach compared with the control. Together, these results show that CIHH alters endothelium-dependent vasodilation.

Asunto(s)

Acetilcolina/farmacología , Mal de Altura/fisiopatología , Altitud , Nitroprusiato/farmacología , Vasodilatación/efectos de los fármacos , Mal de Altura/sangre , Animales , Presión Sanguínea , Peso Corporal , Enfermedad Crónica , Modelos Animales de Enfermedad , Frecuencia Cardíaca , Hematócrito , Masculino , Nitratos/sangre , Nitritos/sangre , Cloruro de Potasio/farmacología , Arteria Pulmonar/efectos de los fármacos , Arteria Pulmonar/fisiopatología , Ratas , Ratas Wistar