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Resumo Objetivo Mapear as evidências disponíveis sobre as ações do óxido nítrico na fisiopatologia da sepse e sua relação com a gravidade de pacientes sépticos. Método Revisão de escopo de acordo com a metodologia do Joanna Briggs Institute. Realizou-se busca por estudos que evidenciaram as ações do óxido nítrico na sepse e se o seu aumento está associado à gravidade de pacientes sépticos. Dois revisores independentes fizeram o mapeamento das informações utilizando um instrumento de extração de dados previamente elaborado. Os dados foram analisados quanto à sua relevância, sendo posteriormente extraídos e sintetizados. Resultados De 1342 estudos, 11 foram incluídos na revisão. O primeiro foi publicado em 2017 e o último, em 2022. A maioria foi desenvolvida nos Estados Unidos, na China e na Alemanha. Os estudos apresentaram informações referentes as ações do óxido nítrico, sintetizando sua biodisponibilidade e os inibidores endógenos relacionados a sua produção, além de abordarem a relação do óxido nítrico com a gravidade da sepse. Conclusão A produção de óxido nítrico fisiológico durante a sepse atua como protetor vascular, principalmente na microcirculação, porém, em altas concentrações, contribui para a disfunção vascular, que subverte a fisiologia da regulação da pressão arterial, causando profunda vasodilatação e hipotensão refratária e aumentando a gravidade de pacientes sépticos.

Introdução: a hanseníase é uma doença in fecciosa crônica causada pelo Mycobacterium leprae (M. leprae), um parasita intracelular obrigatório. Assim, a resistência do hospedeiro a esse patógeno depende da imunidade celular. O uso de modelos experimentais tem permitido o estudo da hanseníase do ponto de vista imunológico, microbiológico e terapêutico, entretanto, as diferenças na progressão da infecção entre os modelos mais empregados (camundongos imunocompetentes, BALB/c, e camundongos congenitamente atímicos, nude) são pouco estudadas. Objetivo: comparar a evolução da infecção pelo M. leprae em camundongos BALB/c e nude quanto à multiplicação bacilar e avaliação do perfil inflamatório sistêmico pela quantificação sérica de citocinas e óxido nítrico (NO). Métodos: os camundongos foram inoculados com M. leprae nos coxins plantares e avaliados aos 3, 5 e 8 meses após a infecção. Resultados: camundongos nude apresentaram multiplicação bacilar progressiva nos coxins plantares. Em camundongos BALB/c, o número de bacilos foi maior aos 5 meses. Em relação à quantificação de citocinas, nos camundongos BALB/c houve aumento de IL-2 e IL-17A e diminuição de IL-6 e NO aos 8 meses de inoculação. Nos camundongos nude, verificou-se o aumento do TNF aos 8 meses de inoculação e manutenção dos níveis de NO. Conclusão: os resultados encontrados sugerem que em camundongos BALB/c ocorre a ativação de uma resposta imune capaz de controlar a multiplicação do M. leprae, em contrapartida em camundongos nude a infecção é progressiva a despeito de altos níveis de TNF.

Introducción. La periodontitis es una enfermedad inflamatoria que afecta los tejidos de soporte dental; los efectos del exceso de óxido nítrico pueden contribuir a los síntomas de la periodontitis. Objetivo. Determinar la concentración de óxido nítrico en el suero de los pacientes con periodontitis agresiva y crónica generalizada, y compararla con la de individuos sanos de población mexicana. Materiales y métodos. Se trata de un estudio de casos y controles. Se incluyeron 69 individuos de la Clínica de Posgrado de Periodoncia del Centro Universitario de Ciencias de la Salud de la Universidad de Guadalajara. Se dividieron en tres grupos: pacientes con periodontitis crónica generalizada (GCP, n=19), pacientes con periodontitis agresiva generalizada (GAP, n=11) e individuos sanos periodontalmente (HS, n=39). Se obtuvo el consentimiento informado de todos los participantes. Se utililizó la prueba ELISA para medir la concentración de óxido nítrico en suero. Resultados. Las concentraciones de óxido nítrico observadas fueron mayores en el grupo GCP (462,57 ± 16,57 μmol/L) que en los grupos GAP (433,84 ± 18,61 μmol/L) y HS (422,46 ± 12,07 μmol/L). La comparación entre HS y GCP mediante la prueba estadística t de Student (una cola), mostró diferencias significativas (p

Copyright of Boletín Latinoamericano y del Caribe de Plantas Medicinales y Aromáticas is the property of Universidad de Santiago de Chile and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Universitas Scientiarum is the property of Pontificia Universidad Javeriana and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Biomédica: Revista del Instituto Nacional de Salud is the property of Instituto Nacional de Salud of Colombia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Arquivos Brasileiros de Oftalmologia is the property of Arquivos Brasileiros de Oftalmologia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Resumo Fundamento O nitrato inorgânico (NO3–) da dieta pode fornecer substrato fisiológico para reduzir o nitrito (NO2–) a óxido nítrico (NO) independente do endotélio. Estudos sugerem que o NO3– inorgânico tem efeitos benéficos na saúde cardiovascular. Objetivos Este estudo avaliou os efeitos agudos de 500 mL de suco de beterraba rico em nitrato (SB; contendo 11,5mmol NO3–) na pressão arterial e na função endotelial em pacientes hipertensos tratados. Métodos Estudo cruzado, randomizado, controlado por placebo foi realizado em pacientes hipertensos tratados (n=37; mulheres=62%) que foram submetidos à avaliação clínica e nutricional, avaliação dos parâmetros hemodinâmicos centrais e reatividade microvascular. O nível de significância foi p

Resumo Fundamento As células progenitoras endoteliais (CPEs) desempenham um papel importante na manutenção da função endotelial. A síndrome metabólica (SM) está associada à disfunção das CPEs. Embora o exercício físico tenha um impacto benéfico na atividade das CPEs, seu mecanismo ainda não está completamente esclarecido. Objetivo O objetivo deste estudo é investigar os efeitos do exercício físico nas funções das CPEs e os mecanismos subjacentes em pacientes com SM. Métodos Os voluntários com SM foram divididos em grupo exercício (n=15) e grupo controle (n=15). Antes e após 8 semanas de treinamento físico, as CPEs foram isoladas do sangue periférico. Foram feitos o ensaio de unidades formadoras de colônias (UFC), o ensaio de formação de tubos, a expressão proteica do óxido nítrico sintase endotelial (eNOS), da fosfatidilinositol-3-quinase (PI3-K) e da proteína quinase B (AKT). Considerou-se um valor de probabilidade

A sepse e suas seqüelas são a maior causa de morte em unidades de tratamento intensivo gerais. A sua incidência é crescente e os pacientes acometidos pela síndrome são cada vez mais complexos. O seu entendimento é ainda incompleto e, portanto, a sua terapia é limitada. A resposta inflamatória do hospedeiro a diferentes agressões por microorganismos ou pelos produtos destes é de tal complexidade que a torna o maior desafio no tratamento de pacientes críticos. As nove publicações aqui resumidas são contribuições para o estudo da sepse nos aspectos epidemiológicos, fisiopatológicos e de tratamento.

Our aim was to perform an initial assessment of the polymorphic patterns of the PIN1 gene in patients with coronary heart disease (CHD). The PIN1-encoded protein (Pin1) suppresses eNOS-NO signaling and may impair cardiovascular function. Blood collection, DNA extraction, PCR amplification and gene sequencing were performed for thirty CHD participants living in central China, focusing on nine single nucleotide polymorphisms (SNPs). Their genetic linkages were revealed and their allele frequencies were compared with SNP data from the NCBI. Three major linkage patterns were identified: [1.rs2287839-5.rs2233682], [3.rs2233679-4.rs1077220–8.rs2287838] and [6.rs889162-7.rs2010457], suggesting correlated involvement in CHD and possible simultaneous genetic origin in ancient times. The frequencies of six SNPs are consistent with the NCBI data, while the frequencies of three SNPs (2.rs2233678, 4.rs1077220 and 9.rs4804461) are not consistent with the NCBI. Especially, the 3.rs2233679–4.rs1077220 linkage is different from other populations worldwide and may be an interesting genetic characteristic of Chinese CHD patients. Predictably, 1.rs2287839, 2.rs2233678, 3.rs2233679 and 5.rs2233682 may be strongly associated with CHD risk, although this requires future verification. The PIN1 SNP linkages lay a new genetic foundation for discovering novel molecular mechanisms of CHD and for exploring PIN1-based targeted treatment of CHD with nitric oxide regulatory therapies in clinical practice. Resumo: O objetivo deste estudo é avaliar os polimorfismos do gene PIN1 em doentes com doença arterial coronária (DAC). A proteína codificada pelo gene PIN1 (Pin1) suprime a sinalização eNOS-NO e pode afetar a função cardiovascular. Foram incluídos 30 indivíduos com DAC, residentes na China central, a quem foi recolhido sangue, extraído e amplificado o DNA por PCR. Foram estudados nove polimorfismos de nucleótidos únicos (SNPs) do gene PIN1. As suas associações genéticas foram estudadas e as frequências de alelo foram comparadas com os dados de SNPs do NCBI. Foram identificados três grandes padrões de linkage: [1.rs2287839-5.rs2233682], [3.rs2233679-4.rs107220-8.rs2287838] e [6.rs889162-7.rs2010457], sugerindo o seu envolvimento na DAC e possível origem genética simultânea histórica. As frequências de seis dos SNPs foram consistentes com os dados do NCBI, enquanto as frequências de três dos SNPs (2.rs2233678, 4.rs1077220 e 9.rs4804461) não foram consistentes com o NCBI. Especificamente, a ligação 3.rs2233679-4.rs1077220 é diferente de outras populações mundiais e poderá constituir uma característica genética específica dos doentes chineses com DAC. Previsivelmente, 1.rs2287839, 2.rs2233678, 3.rs2233679 e 5.rs2233682 podem estar particularmente associados ao risco de DAC, requerendo validação ulterior. As ligações PIN1-SNP estabelecem uma nova base genética para a descoberta de novos mecanismos moleculares da DAC e para explorar o tratamento de precisão da DAC com medicamentos reguladores do óxido nítrico, baseado nos polimorfismos do gene PIN1.

Skeletal muscle injury is an acute inflammatory condition caused by an inflammatory response. To reduce inflammatory cell infiltration and relieve skeletal muscle injury, efficient treatment is urgently needed. Nitric oxide is a free radical molecule reported to have anti-inflammatory effects. In this study, we showed that NO could inhibit the inflammatory response of C2C12 cells in vitro and protect rat skeletal muscle injury from notexin in vivo. NO synthase inhibitor (L-NG-Nitroarginine Methyl Este, L-NAME) and NO donor (sodium nitroprusside dehydrate, SNP) were used to explore the vital role of lipopolysaccharides (LPSs) in LPS-stimulated C2C12 myoblasts. The expression of IL-18 and IL-1b was upregulated by L-NAME and downregulated by SNP, as indicated by the ELISA results. NO can reduce ASC, Caspase-1, and NLRP3 mRNA and protein levels. Furthermore, NO was detected in the rat model. The results of immunohistochemical staining showed that the production of DMD decreased. We conducted qRT-PCR and western blotting to detect the expression of Jo-1, Mi-2, TLR2, and TLR4 on day 6 post injury following treatment with L-NAME and SNP. The expression of Jo-1, Mi-2, TLR2, and TLR4 was upregulated by L-NAME and significantly reversed by SNP. NO can alleviate C2C12 cell inflammatory responses and protect rat skeletal muscle injury from notexin. [ABSTRACT FROM AUTHOR]

Copyright of Scientia Medica is the property of EDIPUCRS - Editora Universitaria da PUCRS and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Ayanin (3,7,4'-Tri-O-methylquercetin) and 3,7-Di-O-methylquercetin (DMQ) are the main active metabolites isolated by bioguided fractionation from Croton schiedeanus, species known popularly in Colombia as "almizclillo", which has been studied in experimental models in rats, exerting vasodilator and antihypertensive effects. Also, when the effect of these flavonoids was studied separately, important vasodilation was observed. Objective: To evaluate whether flavonoids from Croton schiedeanus have synergistic vasodilator properties when different combinations are used in isolated aorta rings. Methods: Cumulative concentrations of ayanin (10-8 M - 6x10-5 M or 0.01 μM - 60 μM) were assayed in the absence and presence of an increasing concentration of 3,7-Di-O-methylquercetin (DMQ) (10-8 - 3x10-5 M or 0.01-30 μM) in isolated rings from Wistar rats, pre-contracted with phenylephrine. The concentration-response curve with the maximal effect was compared with that obtained by Croton schiedeanus whole ethanolic extract (10-6 - 3x10-4 g/mL). Also, this combination was assayed in the presence of the nitric oxide synthetase inhibitor L-NAME (10-4 M) and the guanylate cyclase inhibitor methylene blue (10-4 M) to assess the role of the NO/cGMP pathway in this interaction. Results: Ayanin and DMQ display a dual interaction in vascular relaxant response: agonism at higher concentration ranges (10-6 - 3x10-5 M or 1-30 μM) and antagonism at lower concentration ranges (10-8 - 3x10-7 M or 0.01-0.3 μM). The efficacy at the highest concentration was greater than that obtained by the whole extract (Emax: 98.4% vs. 33.9%). This response was decreased but not reverted in the presence of L-NAME and methylene blue. Thus, the vasodilator effect of this combination does not depend entirely on the NO/cGMP cyclic pathway. Conclusion: The combined use of appropriate concentrations of these flavonoids could represent an advantage over Croton schiedeanus whole extract for vasodilator purposes. [ABSTRACT FROM AUTHOR]

The aim of this study was to determine the relationship of autophagy-enhancing rapamycin (RAPA) and autophagyinhibitor 3-methyladenine (3-MA) with Nitric oxide synthases (NOS) in Cisplatin (CIS)-induced neurotoxicity in rats. Rats were divided into 4 groups (n=10): Control was applied saline, CIS (a single dose of 8mg/kg intraperitoneal (i.p.) on 7th day of experiment), RAPA+CIS (2 mg/kg/i.p. RAPA per day and 8 mg/kg/i.p. CIS on 7th day), 3-MA+CIS (15 mg/kg/i.p. 3-MA per day and 8 mg/kg/i.p. CIS on 7th day). Rats were sacrificed under anesthesia. Brain tissues were evaluated histopathologically. eNOS, Inos, nNOS and MAP 2 immunostaining were performed to determine the expression levels of these proteins among groups. Superoxide dismutase (SOD), Catalase (CAT), Malondialdehyde (MDA) and Interleukin IL-6 levels in brain tissue and serum nitric oxide (NO) level were measured by ELISA assay. In histopathological evaluation, neurodegeneration was seen in the CIS group. There was an increase in eNOS, iNOS and nNOS immunostaining in CIS group. While MAP2 immunostaining of the CIS group decreased. There was a decrease in SOD and CAT levels of brain tissue in CIS group. However, there was an increase in MDA, IL-6 and NO levels of brain tissue in CIS group. We found that antioxidant capacity increase while, inflammation and nitric oxide levels decreased in the RAPA-treated group. 3-MA does not have a significant effect. We suggest that CIS-induced neurotoxicity is more effective than Rapa 3-MA and may also be linked to NOS enzymes. [ABSTRACT FROM AUTHOR]

Copyright of Revista Argentina de Cardiología is the property of Sociedad Argentina de Cardiologia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The aim of this study was to evaluate the effects of citrulline malate (CIT) supplementation on aerobic and muscular endurance in young adult males. Eighteen young adult men (age: 21.5 ± 2.7 years) were randomized into two groups (Citrulline malate - CIT and Placebo - PLA; N = 9/group) and received the respective supplements for 7 days. The CIT group was supplemented with 6 g CIT + 6 g dextrose (total: 12 g), while the PLA group received the same amount (12 g) of dextrose. At the pre- and post-supplementation, the following variables were analyzed: aerobic (maximal treadmill test, Tmax) and muscle (repetitions maximum test, Rmax) endurance tests, as well as mean and maximum heart rate (HR) in Tmax and ratings of perceived exertion (PSE) in Rmax. No significant (P > 0.05) differences were found between CIT and PLA groups in time until exhaustion in Tmax, total repetitions in Rmax, maximal HR and PSE from pre- to post-supplementation. The mean HR was statistically lower (P < 0.05) in the CIT group compared to the PLA in the Tmax. In conclusion, supplementation of CIT (6 g / day) does not improve aerobic and muscular endurance, as well as maximal HR or PSE in healthy young adults, despite reducing the mean HR during the maximal incremental test. [ABSTRACT FROM AUTHOR]

Los nitratos y nitritos son compuestos químicos inorgánicos derivados del nitrógeno, que se encuentran naturalmente en alimentos vegetales y de manera adicionada en algunos productos cárnicos procesados. Su presencia en la dieta se ha relacionado históricamente con un alto riesgo de desarrollar cáncer en diferentes tejidos debido a su capacidad de transformarse en N-nitrosaminas, altamente carcinogénicas. El objetivo de este artículo es revisar el impacto que tiene para la salud humana la ingesta de nitratos y nitritos alimentarios, en relación con su procedencia de fuentes naturales o de productos procesados a los que han sido añadidos como aditivos químicos.

É crescente a procura por suplementos nutricionais que aumentem a produção de óxido nítrico (NO). Uma das vias de obtenção de NO é através da ingestão de nitrato. A suplementação de nitratos visando o aumento de desempenho é recente na história da fisiologia do exercício, a primeira publicação a respeito da suplementação de nitratos foi em 2007 e em 2009 sobre a suplementação de nitratos através do suco de beterraba. O objetivo do presente estudo foi avaliar o efeito da suplementação do suco de beterraba no desempenho em exercícios anaeróbicos de atletas praticantes de futebol. A amostra foi composta por oito atletas da categoria Júnior de um clube de futebol. Estes foram suplementados com 500ml/dia de suco de beterraba durante sete dias consecutivos. E realizaram testes de força utilizando uma cadeira extensora para avaliar o efeito da suplementação. O aumento no número de repetições observado no presente estudo não foi significativo (p>0,05). O IMC médio encontrado foi 22,56±1,09 kg/m2, 87,5%dos participantes foram classificados como eutróficos, e 12,5% em sobrepeso. Foram observadas ingestões insuficientes de calorias, cálcio, B9, potássio, fibras e magnésio, além de um padrão dietético hipoglicídico, tais ingestões insuficientes podem prejudicar o desempenho esportivo e o resultado deste estudo. Apesar de existirem evidências demonstrando que a suplementação de suco de beterraba promove melhoras no desempenho em exercícios anaeróbicos, no presente estudo não foi observado melhora significativa no teste de força.

RESUMEN Introducción: El asma ocupacional (AO) es la enfermedad respiratoria de origen laboral más prevalente en los países desarrollados. Ocurre principalmente por exposición inhalatoria a agentes como el isocianato, contenido en las pinturas utilizadas en el sector automotriz. Su diagnóstico depende de varios factores y está en estudio la utilidad de la fracción espirada de óxido nítrico (FeNO) como marcador de inflamación respiratoria, siendo un método sencillo, rápido y no invasivo. Este trabajo resume la evidencia científica sobre la utilidad de FeNO en la evaluación del asma inducida por isocianato. Material y Métodos: Se realizó una revisión sistemática de la literatura científica publicada en 6 bases de datos, utilizando ecuaciones de búsqueda en términos MeSH. Se procedió a un cribado de las referencias y se seleccionaron los artículos basándonos en los objetivos del estudio y en los de mayor evidencia científica según SIGN. Resultados: Se recuperaron 45 referencias y se incluyeron 8 en la revisión; 7 de ellos fueron de diseño transversal. Hubo asociación estadísticamente significativa entre hiperreactividad bronquial (HRB) y FeNO en trabajadores expuestos a isocianato en todos los artículos, con excepción de uno. Conclusiones: A pesar de las limitaciones en los estudios revisados en cuanto al tipo de diseño, tamaño de la muestra y objetivos, se demuestra que existe evidencia científica que apoya la utilidad del FeNO en la evaluación del asma ocupacional por isocianatos.

The impact of L-norvaline, a non-selective arginase inhibitor, on the state of the resected liver of Wistar strain white male rat, was evaluated. The resection of the liver was made on the second day of the experiment to the extent of 70%. Lnorvaline ("WIRUD JmgH", Hamburg) was intragastrically administered, at a daily dose of 18mg/kg for the first seven days of the experiment, every 48 hours. The effect of the drug on the state of the resected liver was assessed according to the mortality rate, time of the volume recovery, the structure and functions of the organ. The mortality rate was being assessed in the experimental animal groups for the first ten days after the surgery. The animals were withdrawal from the experiment on the second, seventh, fourteenth, twentyfirst, and twenty-eight days after the surgery. The cytolysis degree was assessed according to the AlAT, AsAT, and LDH indexes in the blood of the experimental animals, by an ultraviolet kinetic method. The synthesis function of the liver was evaluated according to the coagulogram indexes (APPT, INR, fibrinogen). The level of microcirculation in the liver was determined by laser doppler fluorometry. The morphological study was performed on the material of the standard liver sites taken after the animal had been withdrawal from the experiment. It was shown, that the non-selective arginase inhibitor, L-norvaline, stimulates liver regeneration after resection, which is manifested by decreased lethality, a significant decrease in the post-resection liver failure in comparison with the control group; significant earlier restoration of the volume, structure, and functions of the resected organ compared with the control group. [ABSTRACT FROM AUTHOR]

The relevance of the study is due to the prevalence and increase in the incidence of endometriosis, especially in young patients, its influence on reproductive function, and the lack of reliable non-invasive diagnosis of the disease and its stages. There are no unified views on the etiology and multifactorial pathogenesis of this disease. This article is aimed at revealing the mechanisms of the formation of endometriosis stages basing on the study of the effect of cytokines production, nitric oxide metabolites and lipid metabolism. The main approach to study this problem is both to investigate systemic (blood serum) and local (peritoneal fluid) levels, their comparison. This allows comprehensive consideration of the pathogenesis of the disease and determination of the value of the mentioned biologically active factors depending on the stages of the disease. The article presents new data on the content of high- and low-density lipoproteins, cholesterol, transforming growth factor β1 and tumor necrosis factor α, the content of nitric oxide metabolites and their clinical interpretation is given according to the stages of the disease. The materials of the article are of practical value for researchers of endometriosis and practicing obstetrician-gynecologists. [ABSTRACT FROM AUTHOR]

Copyright of Revista Brasileira de Medicina do Esporte is the property of Redprint Editora Ltda. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The effect of ascorbic acid (AA) on the formation of nitric oxide (NO) in peritoneal macrophages of SHK line mice was studied. ESR and UV spectroscopy revealed a significant increase in oxide formation in a suspension of macrophages with AA incubated at room temperature. In ESR studies, hemoglobin added to a suspension of macrophages was used as a NO trap, and the resulting nitric oxide was detected by the formation of hemoglobin complexes Heme-NO. The quantitative assessment showed that under these conditions, under the action of AA, 1.5x109 molecules of NO per cell are produced in macrophages. The increase in nitric oxide synthesis under the action of AA was also established by UV spectroscopy in the supernatant after incubation of MP with AA. Considering the known data on the cytotoxic effect of NO on viruses and bacteria, it is assumed that the effect of increasing nitric oxide synthesis in peritoneal, tissue MP and leukocytes under the action of AA is the main in the preventive and therapeutic effect of AA in a number of diseases, such as a sick of cold. [ABSTRACT FROM AUTHOR]

El manejo farmacológico de la hipertensión arterial pulmonar se basa en agentes que actúan en tres vías principales: endotelina 1, prostaglandina I2 y óxido nítrico. La mayoría de estudios clínicos para aprobación de medicamentos desarrollados para tratar esta condición, han sido cortos y enfocados en el cambio en la caminata de 6 minutos. Al tener en cuenta que las diferentes formas de hipertensión arterial pulmonar tienen como denominador común para las alteraciones moleculares y celulares el entrecruzamiento celular con la pared vascular asociado a procesos inflamatorios e inmunes inapropiados, disbalance entre la síntesis y degradación de matriz extracelular, alteraciones genéticas (gen BMPR2 en hipertensión arterial pulmonar hereditaria) y epigenéticas, se requiere un mejor entendimiento de la fisiopatología de la enfermedad, lo cual permitirá desarrollar nuevos tratamientos o intervenciones en estos pacientes en cada uno de estos niveles.

La investigación y el avance en el tratamiento de la hipertensión arterial pulmonar han permitido modificar la historia natural de esta enfermedad. El pilar del tratamiento es el empleo de terapias con vasodilatadores pulmonares específicos, pero también habrán de tenerse en cuenta otras medidas como la actividad física, el apoyo psicológico, la anticoagulación, el tratamiento diurético, la oxigenoterapia o el tratamiento anticonceptivo. Previo a iniciar cualquier tipo de tratamiento específico se requiere un estudio de vasorreactividad aguda del lecho vascular pulmonar, ya que los pacientes con respuesta positiva podrían beneficiarse del tratamiento con calcio-antagonistas. En caso de respuesta negativa o no ser respondedores sostenido, en la actualidad se dispone de fármacos frente a las tres principales vías metabólicas implicadas en el desarrollo de la enfermedad, a saber, prostanoides (epoprosterenol, treprostinil e iloprost, selexipag), antagonistas de los receptores de la endotelina o ARE (bosentan, macitentan y ambrisentan), inhibidores de la fosfodiesterasa 5 o IPDE5 (sildenafilo y tadalafilo) y estimuladores de la guanilato ciclasa (riociguat). La elección del fármaco de inicio, ya sea en monoterapia o en combinación, dependerá de múltiples factores como clase funcional, comorbilidades, interacciones con otros fármacos, tolerabilidad y seguridad, y finalmente de la disponibilidad y las preferencias.

Introdução: O resveratrol é uma fitoalexina natural cujos principais benefícios devem-se às suas propriedades antiinflamatórias e antioxidantes. Os seus efeitos sugerem que este é um suplemento útil para a redução da inflamação, podendo desempenhar um papel fundamental na prevenção das doenças cardiovasculares. Este promove a vasodilatação pela indução da síntese de óxido nítrico (NO), possui atividade antitrombótica e evita a agregação plaquetária. O fator de crescimento endotelial vascular (VEGF) é responsável pela angiogénese, sendo a sua expressão influenciada pelo resveratrol. Objetivos: Avaliar o efeito do resveratrol no perfil vascular pela determinação da pressão arterial e dos biomarcadores interleucina-6 (IL-6), proteína C reativa (PCR), VEGF e NO. Material e Métodos: 27 alunos com idades compreendidas entre os 18 e os 22 anos foram divididos em grupo controlo (GC) e grupo de intervenção (GI), que consumiram placebo e 100 mg de resveratrol por dia, respetivamente, durante 1 mês. A pressão arterial foi medida com aparelho automático validado. Os níveis de PCR foram obtidos por imunoturbidimetria, os de IL-6 e VEGF por slot blot e a quantificação de NO por espectrofotometria. Resultados: Entre os grupos observou-se uma diminuição da pressão arterial braquial e central (??0.05). A variação negativa no NO apresentou-se superior no GC apesar das diferenças não serem significativas (p>0,05). Nos restantes marcadores avaliados não se observaram diferenças significativas. Conclusões: A ingestão regular de resveratrol parece ser uma abordagem preventiva a nível vascular, dado que modula positivamente o perfil vascular, reduzindo a pressão arterial. A variação nos níveis de NO poderá ajudar a explicar os benefícios verificados.

Seed germination and early seedling growth are sensitive to drought stress in wheat. A factorial experiment was arranged based on a completely randomized design with three replicates to study the impacts of TiO2 nanoparticles (TiO2 NPs: 0, 500, 1000 and 2000 mg.L) and sodium nitroprusside (SNP: 0 and 100 µM), as NO donor, on seed germination and seedling growth of wheat under polyethylene glycol (PEG)-induced drought stress (0, -0.4 and -0.8 MPa). Our results revealed that PEG-stimulated drought stress significantly decreased germination percentage (GP), germination energy (GE), germination rate (GR), root length (RL), shoot length (SL), root fresh weight (RFW), shoot fresh weight (SFW) and vigor index (VI) but increased mean germination time (MGT) in wheat seeds. However, application of TiO2 NPs and SNP alone or in combination significantly enhanced GP, GE, GR, RL, SL, RFW, SFW and VI up to 23.72%, 50%, 33.74%, 85.38%, 93.28%, 73%, 91.91% and 91.04% respectively, but significantly reduced MGT up to 28.36% under severe drought stress. Our results showed that application of TiO2 NPs and SNP alone or in combination can significantly alleviate the adverse effects of PEG-stimulated drought stress on seed germination and early seedling growth of wheat. [ABSTRACT FROM AUTHOR]

Objective: To characterize the calcium influx pathways implicated in the sustained elevation of endothelial intracellular calcium concentration, required for the synthesis and release of relaxing factors. Methods: We evaluated the effect of the newly synthesized pyrazole derivatives, described as selective inhibitors for ORAI (BTP2/Pyr2 and Pyr6) and TRPC3 (Pyr3 and Pyr10) channels, upon endothelium- and extracellular calcium-dependent relaxations stimulated by acetylcholine and thapsigargin, in pre-constricted rat thoracic aortic rings. Results: Acetylcholine and thapsigargin responses were completely reverted by Pyr2 and Pyr6 (1 to 3µM). Pyr3 (0.3 to 3µM) caused a rapid reversal of acetylcholine (6.2±0.08mg.s-1) and thapsigargin (3.9±0.25mg.s-1) relaxations, whereas the more selective TRPC3 blocker Pyr10 (1 to 3µM) had no effect. The recently described TRPC4/5 selective blocker, ML204 (1 to 3µM), reverted completely acetylcholine relaxations, but minimally thapsigargin induced ones. Noteworthy, relaxations elicited by GSK1016790A (TRPV4 agonist) were unaffected by pyrazole compounds or ML204. After Pyr2 and Pyr6 pre-incubation, acetylcholine and thapsigargin evoked transient relaxations similar in magnitude and kinetics to those observed in the absence of extracellular calcium. Sodium nitroprusside relaxations as well as phenylephrine-induced contractions (denuded aorta) were not affected by any of pyrazole compounds (1 to 3µM). Conclusion: These observations revealed a previously unrecognized complexity in rat aorta endothelial calcium influx pathways, which result in production and release of nitric oxide. Pharmacologically distinguishable pathways mediate acetylcholine (ORAI/TRPC other than TRPC3/TRPC4 calcium-permeable channels) and thapsigargin (TRPC4 not required) induced calcium influx. [ABSTRACT FROM AUTHOR]

Sildenafil has been used in the treatment of male erectile dysfunction (ED) and recently for pulmonary hypertension. The discovery that PDE-5i is present in the systemic artery endothelium and vascular smooth muscle cells, led researchers to study the additional effects of sildenafil. The pathogenesis of endothelial dysfunction and ED is intimately related through the decrease in the expression and activation of endothelial nitric oxide synthase (NOS) and the physiological actions of nitric oxide (NO). In addition, the reduced biological activity of NO derived from endothelium links atherosclerosis to ED and highlights the role of endothelial dysfunction in the pathogenesis of both conditions. The aim of the present review is to analyze the systemic effects of PDE-5i administration in different experimental models and patients to assess the possible applications that these drugs can have in the near future as a novel treatment in atherosclerosis or as cardioprotector. [ABSTRACT FROM AUTHOR]

This study aims to reveal the role of nitric oxide (NO) in substituting nitrite with lactic acid bacteria. Three lactic acid bacterial strains (L. fermentum JCM1173, L. fermentum IFO3956, Weissella cibaria X31) with nitrite substitution ability were inoculated into fermented sausages, respectively. Results indicated that the ratio of nitrosomyoglobin (NO-Mb) to total pigments was positively correlated with the substitution ability of the strain. UV-visible and resonance Raman spectroscopy suggested the NO-Mb was five-coordinated. In addition, the intracellular NO detected by fluorescent DAF-FM probe showed that W. cibaria X31 had the strongest NO-producing ability. Inhibitory experiments showed that both nitrate reductase and nitric oxide synthase-like protein participated in the NO production. These results indicated the vital role NO played in the substitution through the formation of NO-Mb and demonstrated the sources of NO in lactic acid bacteria preliminarily. [ABSTRACT FROM AUTHOR]

Nitric Oxide (NO) is a relaxing endothelium-derived factor and a potent vasodilator that impacts various systems throughout the body. Proven studies of basal ocular blood flow are regulated by NO, being an important regulator of homeostasis, especially within the uveal tissues. The dysfunction of the production associated with glaucoma due to alteration of the optic nerve head associated to the increase of the intraocular pressure by a deficient trabecular meshwork. NO became an attractive molecule for the treatment of glaucoma due to a modulation of the trabecular meshwork, lowering the neuroprotective intra and ocular pressure for a blood surgery in the head of the optic nerve. [ABSTRACT FROM AUTHOR]

The effects of NO donors on germination under saline stress have been much investigated for many species, however, there are reports that the effect caused by donors are effects of cyanide present. The aim of this study was to evaluate the effects of sodium nitroprusside (SNP) on germination, antioxidative system and lipid peroxidation of Senna macranthera seeds under saline stress. The osmotic potentials of -0.4 and -0.5 MPa of NaCl were used, as well as the concentration of 100 µM of sodium nitroprusside, inactive sodium nitroprusside. Germination rate, imbibition curves, antioxidant enzyme activity, lipid peroxidation, and protein content were evaluated. Similar effects were observed for sodium nitroprusside and inactive sodium nitroprusside, indicating that these effects were related to the release of the cyanide present in sodium nitroprusside. The sodium nitroprusside (SNP) improves the germination of Senna macranthera seeds under salt stress conditions, through release of cyanide. The cyanide favored germination, reducing lipid peroxidation and increasing the activity of the antioxidant enzymes. [ABSTRACT FROM AUTHOR]

La hipertensión pulmonar persistente del recién nacido es el resultado de un fracaso o de una mala adaptación circulatoria al momento de nacimiento; y representa una falla respiratoria aguda con un aumento sostenido de la resistencia vascular pulmonar, generando cortos circuitos extrapulmonares de derecha a izquierda, a través del conducto arterioso y foramen oval, con hipoxemia severa y acidosis secundaria. La clave del tratamiento reside en lograr una rápida mejoría de la oxigenación y dilatación de la arteria pulmonar para revertir los cortos circuitos con el uso de vasodilatadores pulmonares, de los cuales el óxido nítrico es el único agente aprobado por la FDA para su uso en neonatos con hipertensión pulmonar persistente del recién nacido, y debe ser considerado como el tratamiento de primera línea. Esta revisión se centrará en qué es el óxido nítrico y su papel como tratamiento de la hipertensión pulmonar persistente del recién nacido.

Resumo Contexto O treinamento de força com restrição do fluxo sanguíneo (TFRFS) promove adaptações neuromusculares semelhantes às do treinamento de força tradicional utilizando pequenas cargas de treinamento. No entanto, sua repercussão sobre parâmetros antioxidantes e sobre a função vascular precisa ser mais bem compreendida. Objetivos: O objetivo do presente estudo foi investigar o efeito de uma sessão de exercício de força de baixa intensidade com restrição do fluxo sanguíneo, em comparação ao exercício de força de alta intensidade e de baixa intensidade sem restrição do fluxo sanguíneo, sobre os níveis de subprodutos do oxido nítrico e a atividade de enzimas antioxidantes em jovens saudáveis. Métodos: Onze indivíduos jovens realizaram três sessões de exercício de força: baixa intensidade com restrição do fluxo sanguíneo (BIRFS), alta intensidade (AI) ou baixa intensidade (BI). Foram avaliadas a atividade das enzimas antioxidantes catalase (CAT), superóxido dismutase (SOD) e dos metabólitos do óxido nítrico (NOx). Resultados: Não houve modificações nos níveis plasmáticos de NOx nas diferentes condições de exercício (p > 0,05). A atividade da SOD apresentou uma diminuição significativa na condição BIRFS (p < 0,05). A atividade da CAT diminuiu significativamente na condição BI (p < 0.05). Conclusões: A partir do presente estudo sugere-se que uma sessão de treinamento de força de baixa intensidade com restrição do fluxo sanguíneo não reduz a biodisponibilidade do óxido nítrico, bem como não induz desequilíbrio redox em indivíduos jovens saudáveis.

Nitric oxide (NO) is a major neurotransmitter associated with motor control in basal ganglia. Movement disorders, as essential tremor and Parkinson’s disease, are more prevalent on aged individuals. We investigated the effects of aging on neuronal density and diameter/area of nitrergic neurons in samples of striatum (caudate and putamen) and subthalamic nucleus of 20 human brains from normal subjects, stained by histochemistry for NADPH-diaphorase and immunohistochemistry for neuronal NO synthase. Our data showed aging does not modify the neuronal density and size of nitrergic neurons in striatum and subthalamic nucleus. These findings suggest a lack of association between aging and morphologic changes on nitrergic neurons.

Background: Ruthenium (Ru) tetraamines are being increasingly used as nitric oxide (NO) carriers. In this context, pharmacological studies have become highly relevant to better understand the mechanism of action involved. Objective: To evaluate the vascular response of the tetraamines trans-[RuII(NH3)4(Py)(NO)]3+, trans-[RuII(Cl)(NO) (cyclan)](PF6)2, and trans-[RuII(NH3)4(4-acPy)(NO)]3+. Methods: Aortic rings were contracted with noradrenaline (10−6 M). After voltage stabilization, a single concentration (10−6 M) of the compounds was added to the assay medium. The responses were recorded during 120 min. Vascular integrity was assessed functionally using acetylcholine at 10−6 M and sodium nitroprusside at 10−6 M as well as by histological examination. Results: Histological analysis confirmed the presence or absence of endothelial cells in those tissues. All tetraamine complexes altered the contractile response induced by norepinephrine, resulting in increased tone followed by relaxation. In rings with endothelium, the inhibition of endothelial NO caused a reduction of the contractile effect caused by pyridine NO. No significant responses were observed in rings with endothelium after treatment with cyclan NO. In contrast, in rings without endothelium, the inhibition of guanylate cyclase significantly reduced the contractile response caused by the pyridine NO and cyclan NO complexes, and both complexes caused a relaxing effect. Conclusion: The results indicate that the vascular effect of the evaluated complexes involved a decrease in the vascular tone induced by norepinephrine (10−6 M) at the end of the incubation period in aortic rings with and without endothelium, indicating the slow release of NO from these complexes and suggesting that the ligands promoted chemical stability to the molecule. Moreover, we demonstrated that the association of Ru with NO is more stable when the ligands pyridine and cyclan are used in the formulation of the compound.

Background: Nitric oxide (NO) has been largely associated with cardiovascular protection through improvement of endothelial function. Recently, new evidence about modulation of NO release by microRNAs (miRs) has been reported, which could be involved with statin-dependent pleiotropic effects, including anti-inflammatory properties related to vascular endothelium function. Objective: To evaluate the effects of cholesterol-lowering drugs including the inhibitors of cholesterol synthesis, atorvastatin and simvastatin, and the inhibitor of cholesterol absorption ezetimibe on NO release, NOS3 mRNA expression and miRs potentially involved in NO bioavailability. Methods: Human umbilical vein endothelial cells (HUVEC) were exposed to atorvastatin, simvastatin or ezetimibe (0 to 5.0 μM). Cells were submitted to total RNA extraction and relative quantification of NOS3 mRNA and miRs -221, -222 and -1303 by qPCR. NO release was measured in supernatants by ozone-chemiluminescence. Results: Both statins increased NO levels and NOS3 mRNA expression but no influence was observed for ezetimibe treatment. Atorvastatin, simvastatin and ezetimibe down-regulated the expression of miR-221, whereas miR-222 was reduced only after the atorvastatin treatment. The magnitude of the reduction of miR-221 and miR-222 after treatment with statins correlated with the increment in NOS3 mRNA levels. No influence was observed on the miR-1303 expression after treatments. Conclusion: NO release in endothelial cells is increased by statins but not by the inhibitor of cholesterol absorption, ezetimibe. Our results provide new evidence about the participation of regulatory miRs 221/222 on NO release induction mediated by statins. Although ezetimibe did not modulate NO levels, the down-regulation of miR-221 could involve potential effects on endothelial function.

OBJECTIVE To evaluate the effect of using antihypertensive classes of drugs of the calcium channel antagonists and inhibitors of angiotensin-converting enzyme in plasma concentrations of hydrogen sulfide and nitric oxide in patients with hypertension. METHODS Cross-sectional study with quantitative approach conducted with hypertensive patients in use of antihypertensive classes of drugs: angiotensin-converting enzyme inhibitors or calcium channel antagonists. RESULTS It was found that the concentration of plasma nitric oxide was significantly higher in hypertensive patients that were in use of angiotensin-converting enzyme inhibitors (p

Background: Ischemic postconditioning (IPost) is a method of protecting the heart against ischemia-reperfusion (IR) injury. However, the effectiveness of IPost in cases of ischemic heart disease accompanied by co-morbidities such as hypothyroidism remains unclear. Objective: The aim of this study was to determine the effect of IPost on myocardial IR injury in hypothyroid male rats. Methods: Propylthiouracil in drinking water (500 mg/L) was administered to male rats for 21 days to induce hypothyroidism. The hearts from control and hypothyroid rats were perfused in a Langendorff apparatus and exposed to 30 min of global ischemia, followed by 120 min of reperfusion. IPost was induced immediately following ischemia. Results: Hypothyroidism and IPost significantly improved the left ventricular developed pressure (LVDP) and peak rates of positive and negative changes in left ventricular pressure (±dp/dt) during reperfusion in control rats (p < 0.05). However, IPost had no add-on effect on the recovery of LVDP and ±dp/dt in hypothyroid rats. Furthermore, hypothyroidism significantly decreased the basal NO metabolite (NOx) levels of the serum (72.5 ± 4.2 vs. 102.8 ± 3.7 μmol/L; p < 0.05) and heart (7.9 ± 1.6 vs. 18.8 ± 3.2 μmol/L; p < 0.05). Heart NOx concentration in the hypothyroid groups did not change after IR and IPost, whereas these were significantly (p < 0.05) higher and lower after IR and IPost, respectively, in the control groups. Conclusion: Hypothyroidism protects the heart from IR injury, which may be due to a decrease in basal nitric oxide (NO) levels in the serum and heart and a decrease in NO after IR. IPost did not decrease the NO level and did not provide further cardioprotection in the hypothyroid group.

Objective: This study was conducted to reassess the concepts established over the past 20 years, in particular in the last 5 years, about the use of methylene blue in the treatment of vasoplegic syndrome in cardiac surgery. Methods: A wide literature review was carried out using the data extracted from: MEDLINE, SCOPUS and ISI WEB OF SCIENCE. Results: The reassessed and reaffirmed concepts were 1) MB is safe in the recommended doses (the lethal dose is 40 mg/kg); 2) MB does not cause endothelial dysfunction; 3) The MB effect appears in cases of NO up-regulation; 4) MB is not a vasoconstrictor, by blocking the cGMP pathway it releases the cAMP pathway, facilitating the norepinephrine vasoconstrictor effect; 5) The most used dosage is 2 mg/kg as IV bolus, followed by the same continuous infusion because plasma concentrations sharply decrease in the first 40 minutes; and 6) There is a possible "window of opportunity" for MB's effectiveness. In the last five years, major challenges were: 1) Observations about side effects; 2) The need for prophylactic and therapeutic guidelines, and; 3) The need for the establishment of the MB therapeutic window in humans. Conclusion: MB action to treat vasoplegic syndrome is time-dependent. Therefore, the great challenge is the need, for the establishment the MB therapeutic window in humans. This would be the first step towards a systematic guideline to be followed by possible multicenter studies.

This work aimed to evaluate the effects of Metarhizium anisopliae on Diatraea flavipennella and investigate their immune response. Was observed the effect of M. anisopliae against larvae of D. flavipennella sprayed at concentrations of 103, 104, 105 conidia / mL, in which showed differences relative the larval period, extending up to 72.0 days in treatment and 25.0 days in the control. The results for hemocytes revealed that the most frequent cells when sprayed at the concentrations of 103, 105, 107 conidia / mL were the prohemocytes, spherulocytes, plasmatocytes and granulocytes in relation to adipohemocytes and oenocytoids. The level of nitric oxide was different between the control and the concentration 107 spores / mL (24), while the activity of phenoloxidase was similar among treatments in 24 and higher concentration 107 spores / mL (60h). In biochemical profile of hemocytes was a change in carbohydrates, lipids and proteins in response to the fungus. The results indicate that the fungus M. anisopliae can be used in the Integrated Management of D. flavipennella by presenting pathogenicity and interfere with their development even when exposed to small concentrations.

Context Intestinal inflammation can induce a local reduction in oxygen levels that triggers an adaptive response centered on the expression of hypoxia-inducible factors (HIFs). Nitric oxide, a well-described inflammatory mediator, may interfere with hypoxia signaling. Objectives We aimed to evaluate the role of nitric oxide in hypoxia signaling during colonic inflammation. Methods Colitis was induced by single (acute) or repeated (reactivated colitis) trinitrobenzenosulfonic acid administration in rats. In addition, one group of rats with reactivated colitis was also treated with Nw-Nitro-L-arginine methyl ester hydrochloride to block nitric oxide synthase. Colitis was assessed by macroscopic score and myeloperoxidase activity in the colon samples. Hypoxia was determined using the oxygen-dependent probe, pimonidazole. The expression of HIF-1α and HIF-induced factors (vascular endothelial growth factor - VEGF and apelin) was assessed using Western blotting. Results The single or repeated administration of trinitrobenzenosulfonic acid to rats induced colitis which was characterized by a high macroscopic score and myeloperoxidase activity. Hypoxia was observed with both protocols. During acute colitis, HIF-1α expression was not increased, but VEGF and apelin were increased. HIF-1α expression was inhibited during reactivated colitis, and VEGF and apelin were not increased. Nw-Nitro-L-arginine methyl ester hydrochloride blockade during reactivated colitis restored HIF-1α, VEGF and apelin expression. Conclusions Nitric oxide could interfere with hypoxia signaling during reactivated colitis inflammation modifying the expression of proteins regulated by HIF-1α.

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Objective: To evaluate the association between fraction of exhaled nitric oxide (FeNO) values and forced expiratory volume in the first second (FEV1) and the level of asthma control, as proposed by the Global Initiative for Asthma (GINA), in asthmatic children and adolescents attended at the National Institute of Women, Children and Adolescents Health Fernandes Figueira of Fundação Oswaldo Cruz (IFF/FIOCRUZ). Methods: This was a cross-sectional study, with a review of medical records of 90 asthmatics between 7 and 17 years old, who were followed up at the IFF/FIOCRUZ Asthma Outpatient Clinic and were referred to perform respiratory function tests (RFT) between March 2013 and September 2014. After classification according to GINA, patients performed complete spirometry and FeNO measurement. Subsequently, they were separated into two groups: regular and non-regular inhaled corticosteroid (ICS) use, regardless of the ventilatory pattern in spirometry. Results: The association between FEV1 values and the degree of asthma control according to GINA (p=0.001) was observed in all patients, regardless of ICS use, but there was no association between FEV1 and levels of FeNO. Conclusions: The correlation observed between GINA and FEV1 reinforces the importance of spirometry in the clinical follow-up of these patients. Although no association was found between the value of FeNO and the degree of asthma control and FEV1, FeNO may be an early method to detect airway inflammation, even before the symptoms and spirometric changes. [ABSTRACT FROM AUTHOR]

Morphine is one of the naturally occurring phenanthrene alkaloids of opium that induces adverse effects on male reproductive system. Resveratrol is a phytoestrogen and antioxidant of red grape. The main goal is to investigate whether resveratrol could inhibit adverse effects of morphine on sperm cell viability, count, motility as well as testis histology, testosterone hormone and nitric oxide levels in mice. In the present study, 48 male rats were randomly divided into 8 groups (n=6) and were treated intraperitoneally for 14 days with normal saline, resveratrol (2, 8, 20 mg/kg/day), morphine (20 mg/kg/day) and morphine (20 mg/kg/day) + resveratrol (2, 8, 20 mg/kg/day). At the end of experiments, sperm parameters (sperm cell viability, count, motility and morphology), testis weight, the diameter of seminiferous tubules, testosterone hormone level and nitric oxide were analyzed. The data were analyzed by SPSS software for windows (version 20) using one-way ANOVA test followed by Tukey's post hoc test, and P<0.05 was considered significant. The results indicated that morphine administration significantly decreased testosterone level, count, viability and motility of sperm cells and testis weight and increased nitric oxide compared to the saline group (P=0.000). Administration of resveratrol and resveratrol plus morphine significantly increased motility, count and viability of sperm cells, somniferous tubule diameter and testosterone, while it decreased nitric oxide level compared to morphine group (P=0.025). It seems that resveratrol administration could increase the quality of spermatozoa and prevented morphine-induced adverse effects on sperm parameters. [ABSTRACT FROM AUTHOR]