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1.
BMC Gastroenterol ; 21(1): 359, 2021 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-34600475

RESUMO

BACKGROUND: Activation of Adenosine 5'-monophosphate-activated protein kinase/Sirtuin1 (AMPK/SIRT1) exerts an effect in alleviating obesity and gut damage. Sodium nitroprusside (SNP), a nitric oxide (NO) donor, has been reported to activate AMPK. This study was to investigate the effect of SNP on HFD induced gut dysfunction and the mechanism. METHODS: SNP was applied on lipopolysaccharide (LPS) stimulated Caco-2 cell monolayers which mimicked intestinal epithelial barrier dysfunction and HFD-fed mice which were complicated by gut dysfunction. Then AMPKα/SIRT1 pathway and gut barrier indicators were investigated. RESULTS: SNP rescued the loss of tight junction proteins ZO-1 and occludin, the inhibition of AMPKα/SIRT1 in LPS stimulated Caco-2 cell monolayers, and the effects were not shown when AMPKa1 was knocked-down by siRNA. SNP also alleviated HFD induced obesity and gut dysfunction in mice, as indicated by the decreasing of intestinal permeability, the increasing expression of ZO-1 and occludin, the decreasing levels of pro-inflammatory cytokine IL-6, and the repairing of gut microbiota dysbiosis. These effects were complicated by the increased colonic NO content and the activated AMPKα/SIRT1 signaling. CONCLUSIONS: The results may imply that SNP, as a NO donor, alleviates HFD induced gut dysfunction probably by activating the AMPKα/SIRT1 signaling pathway.


Assuntos
Proteínas Quinases Ativadas por AMP , Sirtuína 1 , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Células CACO-2 , Dieta Hiperlipídica , Humanos , Camundongos , Nitroprussiato/farmacologia , Transdução de Sinais , Sirtuína 1/genética , Sirtuína 1/metabolismo
2.
Plant Physiol Biochem ; 167: 337-348, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34392046

RESUMO

Plants do not always have the genetic capacity to tolerate high levels of arsenic (As), which may not only arrest their growth but pose potential health risks through dietary bioaccumulation. Meanwhile, the interplay between the tomato plants and As-NO-driven molecular cell dynamics is obscure. Accordingly, seedlings were treated with As (10 mg/L) alone or in combination with 100 µM sodium nitroprusside (SNP, NO donor) and 200 µM 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO, NO scavenger). Sodium nitroprusside immobilized As in the roots and reduced the shoot translocation by up-regulating the transcriptional expression of the PCS, GSH1, MT2, and ABC1. SNP further restored the growth retardation through modulating the chlorophyll and proline metabolism, increasing NO accumulation and stomatal conductance along with clear crosstalk between the antioxidant activity as well as glyoxalase I and II leading to endogenous H2O2 and MG reduction. Higher PCs and glutathione accumulation helped protect photosynthetic apparatus; however, cPTIO reversed the protective effects of SNP, confirming the role of NO in the As toxicity alleviation.


Assuntos
Arsênio , Lycopersicon esculentum , Antioxidantes , Arsênio/toxicidade , Peróxido de Hidrogênio , Lycopersicon esculentum/metabolismo , Óxido Nítrico , Nitroprussiato/farmacologia , Oxirredução , Estresse Oxidativo , Fitoquelatinas/metabolismo
3.
J Exp Biol ; 224(17)2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34427663

RESUMO

When snakes digest large meals, heart rate is accelerated by withdrawal of vagal tone and an increased non-adrenergic-non-cholinergic tone that seems to stem from circulating blood-borne factors exerting positive chronotropic effects. To investigate whether this tonic elevation of heart rate impairs the ability for autonomic regulation of heart during digestion, we characterised heart rate responses to pharmacological manipulation of blood pressure in the snake Boa constrictor through serial injections of sodium nitroprusside and phenylephrine. Both fasting and digesting snakes responded with a robust tachycardia to hypotension induced by sodium nitroprusside, with digesting snakes attaining higher maximal heart rates than fasting snakes. Both fasting and digesting snakes exhibited small reductions of the cardiac chronotropic response to hypertension, induced by injection of phenylephrine. All heart rate changes were abolished by autonomic blockade with the combination of atropine and propranolol. The digesting snakes retained the capacity for compensatory heart rate responses to hypotension, despite their higher resting values, and the upward shift of the barostatic response curve enables snakes to maintain the cardiac limb of barostatic regulation for blood pressure regulation.


Assuntos
Boidae , Animais , Atropina/farmacologia , Sistema Nervoso Autônomo , Pressão Sanguínea , Frequência Cardíaca , Nitroprussiato/farmacologia , Nervo Vago
5.
Int J Mol Sci ; 22(13)2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34209006

RESUMO

Osteoarthritis (OA) is a common chronic disease with increasing prevalence in societies with more aging populations, therefore, it is causing more concern. S-Equol, a kind of isoflavones, was reported to be bioavailable and beneficial to humans in many aspects, such as improving menopausal symptoms, osteoporosis and prevention of cardiovascular disease. This study investigated the effects of S-Equol on OA progress in which rat primary chondrocytes were treated with sodium nitroprusside (SNP) to mimic OA progress with or without the co-addition of S-Equol for the evaluation of S-Equol's efficacy on OA. Results showed treatment of 0.8 mM SNP caused cell death, and increased oxidative stress (NO and H2O2), apoptosis, and proteoglycan loss. Furthermore, the expressions of MMPs of MMP-2, MMP-3, MMP-9, and MMP-13 and p53 were increased. The addition of 30 µM S-Equol could lessen those caused by SNP. Moreover, S-Equol activates the PI3K/Akt pathway, which is an upstream regulation of p53 and NO production and is associated with apoptosis and matrix degradation. As a pretreatment of phosphoinositide 3-kinases (PI3K) inhibitor, all S-Equol protective functions against SNP decrease or disappear. In conclusion, through PI3K/Akt activation, S-Equol can protect chondrocytes against SNP-induced matrix degradation and apoptosis, which are commonly found in OA, suggesting S-Equol is a potential for OA prevention.


Assuntos
Condrócitos/citologia , Equol/farmacologia , Nitroprussiato/efeitos adversos , Osteoartrite/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Condrócitos/efeitos dos fármacos , Feminino , Regulação da Expressão Gênica , Humanos , Masculino , Modelos Biológicos , Osteoartrite/induzido quimicamente , Osteoartrite/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Cultura Primária de Células , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos
6.
Int J Mol Sci ; 22(9)2021 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-34063297

RESUMO

Our study aimed to examine the effects of hypertension and the chronic administration of the fatty acid amide hydrolase (FAAH) inhibitor URB597 on vascular function and the endocannabinoid system in spontaneously hypertensive rats (SHR). Functional studies were performed on small mesenteric G3 arteries (sMA) and aortas isolated from SHR and normotensive Wistar Kyoto rats (WKY) treated with URB597 (1 mg/kg; twice daily for 14 days). In the aortas and sMA of SHR, endocannabinoid levels and cannabinoid CB1 receptor (CB1R) expression were elevated. The CB1R antagonist AM251 diminished the methanandamide-evoked relaxation only in the sMA of SHR and enhanced the vasoconstriction induced by phenylephrine and the thromboxane analog U46619 in sMA in SHR and WKY. In the sMA of SHR, URB597 elevated anandamide levels, improved the endothelium-dependent vasorelaxation to acetylcholine, and in the presence of AM251 reduced the vasoconstriction to phenylephrine and enhanced the vasodilatation to methanandamide, and tended to reduce hypertrophy. In the aortas, URB597 elevated endocannabinoid levels improved the endothelium-dependent vasorelaxation to acetylcholine and decreased CB1R expression. Our study showed that hypertension and chronic administration of URB597 caused local, resistance artery-specific beneficial alterations in the vascular endocannabinoid system, which may bring further advantages for therapeutic application of pharmacological inhibition of FAAH.


Assuntos
Amidoidrolases/efeitos dos fármacos , Amidoidrolases/metabolismo , Benzamidas/farmacologia , Carbamatos/farmacologia , Endocanabinoides/metabolismo , Hipertensão Essencial/metabolismo , Hipertensão Essencial/terapia , Acetilcolina , Animais , Aorta , Ácidos Araquidônicos , Hipertensão/metabolismo , Masculino , Artérias Mesentéricas/efeitos dos fármacos , Nitroprussiato , Alcamidas Poli-Insaturadas , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Receptores de Canabinoides , Vasoconstrição , Vasodilatação/efeitos dos fármacos
7.
Food Chem ; 362: 130193, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34082290

RESUMO

Lignin is an important component of the healing tissue in fruits. In this study, we treated muskmelon (Cucumis melo L. cv. "Manao") fruit with exogenous nitric oxide (NO) donor sodium nitroprusside (SNP) to observe and analyze its effect on lignin synthesis and accumulation during healing. Results showed that SNP treatment enhanced the contents of endogenous NO and H2O2, increased the activities of phenylalanine ammonia lyase, cinnamate 4 hydroxylase, cinnamyl alcohol dehydrogenase, and peroxidase, and raised the contents of sinapyl alcohol, coniferyl alcohol, coumaryl alcohol, and lignin. SNP augmented the hardness of the healing tissue and decreased its resilience, springiness, and cohesiveness. In addition, SNP treatment effectively reduced the weight loss and disease index of wounded muskmelons. All these results suggest that lignin metabolism mediated by NO play a crucial role in wound healing of muskmelons.


Assuntos
Cucumis melo/química , Cucumis melo/metabolismo , Frutas/química , Lignina/biossíntese , Nitroprussiato/química , Oxirredutases do Álcool , Frutas/metabolismo , Peróxido de Hidrogênio/metabolismo , Óxido Nítrico/química , Óxido Nítrico/metabolismo , Doadores de Óxido Nítrico/química , Peroxidase/metabolismo , Fenóis/metabolismo , Fenilalanina Amônia-Liase/metabolismo , Fenilpropionatos/metabolismo , Proteínas de Plantas/química , Proteínas de Plantas/metabolismo
8.
Molecules ; 26(11)2021 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-34073534

RESUMO

Schizophrenia is a severe psychiatric disorder affecting up to 1% of the worldwide population. Available therapy presents different limits comprising lack of efficiency in attenuating negative symptoms and cognitive deficits, typical features of schizophrenia and severe side effects. There is pressing requirement, therefore, to develop novel neuroleptics with higher efficacy and safety. Nitric oxide (NO), an intra- and inter-cellular messenger in the brain, appears to be implicated in the pathogenesis of schizophrenia. In particular, underproduction of this gaseous molecule is associated to this mental disease. The latter suggests that increment of nitrergic activity might be of utility for the medication of schizophrenia. Based on the above, molecules able to enhance NO production, as are NO donors, might represent a class of compounds candidates. Sodium nitroprusside (SNP) is a NO donor and is proposed as a promising novel compound for the treatment of schizophrenia. In the present review, we intended to critically assess advances in research of SNP for the therapy of schizophrenia and discuss its potential superiority over currently used neuroleptics.


Assuntos
Antipsicóticos/farmacologia , Doadores de Óxido Nítrico/farmacologia , Nitroprussiato/farmacologia , Esquizofrenia/tratamento farmacológico , Animais , Comportamento Animal , Encéfalo/efeitos dos fármacos , Transtornos Cognitivos/tratamento farmacológico , Humanos , Camundongos , Atividade Motora/efeitos dos fármacos , Óxido Nítrico/farmacologia , Nitroprussiato/química , Ensaios Clínicos Controlados Aleatórios como Assunto , Ratos
9.
Vet J ; 273: 105694, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34148609

RESUMO

Electrical impedance tomography (EIT) provides clinically useful lung images; however, it would be an advantage to extract additional cardiovascular information from the data. The aim of this study was to evaluate if cardiac-related changes measured by EIT can be used to measure pulse rate (PR) under physiological as well as high and low blood pressure states in anaesthetised horses. Electrical impedance tomography data and PR from seven horses anaesthetised in dorsal recumbency were recorded over 1 min during mechanical ventilation and 1 min of apnoea. Data were collected at four measurement time points; before and during intravenous administration of nitroprusside and phenylephrine, respectively. Nine pixels, estimated to represent the heart, were chosen from the EIT image. A novel algorithm detected peaks of impedance change for these pixels over 10 s intervals. Concurrent PR measured using an invasive blood pressure trace, was recorded every 10 s. EIT- and pulse-rate data were compared using Bland-Altman assessment for multiple measurements on each horse. Overall, 288 paired datasets from six of seven horses were available for analysis. There was excellent agreement for baseline measurements, as well as during hypertension and hypotension, with a bias of -0.26 and lower and upper limit of agreement at -2.22 (95% confidence intervals [CI], -2.89 to -1.86) and 1.69 (95% CI, 1.34-2.36) beats per min, respectively. EIT can be used to evaluate PR using cardiac-related impedance changes. More work is required to determine bias that might occur in anaesthetised horses in other recumbencies or clinical situations.


Assuntos
Anestesia/veterinária , Impedância Elétrica , Frequência Cardíaca , Cavalos , Anestésicos Intravenosos/administração & dosagem , Animais , Diazepam/administração & dosagem , Hipertensão/veterinária , Hipotensão/veterinária , Ketamina/administração & dosagem , Nitroprussiato/administração & dosagem , Fenilefrina/administração & dosagem , Tomografia/métodos , Tomografia/veterinária
10.
Molecules ; 26(10)2021 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-34064778

RESUMO

Kynurenic acid (KYNA) is derived from tryptophan, formed by the kynurenic pathway. KYNA is being widely studied as a biomarker for neurological and cardiovascular diseases, as it is found in ischemic conditions as a protective agent; however, little is known about its effect after ischemia-reperfusion in the vascular system. We induced ischemia for 30 min followed by 5 min reperfusion (I/R) in the rat aorta for KYNA evaluation using functional assays combined with proteomics. KYNA recovered the exacerbated contraction induced by phenylephrine and relaxation induced by acetylcholine or sodium nitroprussiate in the I/R aorta, with vessel responses returning to values observed without I/R. The functional recovery can be related to the antioxidant activity of KYNA, which may be acting on the endothelium-injury prevention, especially during reperfusion, and to proteins that regulate neurotransmission and cell repair/growth, expressed after the KYNA treatment. These proteins interacted in a network, confirming a protein profile expression for endothelium and neuron repair after I/R. Thus, the KYNA treatment had the ability to recover the functionality of injured ischemic-reperfusion aorta, by tissue repairing and control of neurotransmitter release, which reinforces its role in the post-ischemic condition, and can be useful in the treatment of such disease.


Assuntos
Aorta/patologia , Ácido Cinurênico/uso terapêutico , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/metabolismo , Proteômica , Acetilcolina/farmacologia , Animais , Aorta/efeitos dos fármacos , Aorta/fisiopatologia , Modelos Animais de Doenças , Ácido Cinurênico/farmacologia , Contração Miocárdica/efeitos dos fármacos , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Nitroprussiato/farmacologia , Fenilefrina/farmacologia , Mapas de Interação de Proteínas/efeitos dos fármacos , Ratos Sprague-Dawley , Vasodilatação/efeitos dos fármacos
11.
J Appl Physiol (1985) ; 131(2): 566-574, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-34166116

RESUMO

The vascular endothelium senses and integrates numerous inputs to regulate vascular tone. Recent evidence reveals complex signal processing within the endothelium, yet little is known about how endothelium-dependent stimuli interact to regulate blood flow. We tested the hypothesis that combined stimulation of the endothelium with adenosine triphosphate (ATP) and acetylcholine (ACh) elicits greater vasodilation and attenuates α1-adrenergic vasoconstriction compared with combination of ATP or ACh with the endothelium-independent dilator sodium nitroprusside (SNP). We assessed forearm vascular conductance (FVC) in young adults (6 women, 7 men) during local intra-arterial infusion of ATP, ACh, or SNP alone and in the following combinations: ATP + ACh, SNP + ACh, and ATP + SNP, wherein the second dilator was coinfused after attaining steady state with the first dilator. By design, each dilator evoked a similar response when infused separately (ΔFVC, ATP: 48 ± 4; ACh: 57 ± 6; SNP: 53 ± 6 mL·min-1·100 mmHg-1; P ≥ 0.62). Combined infusion of the endothelium-dependent dilators evoked greater vasodilation than combination of either dilator with SNP (ΔFVC from first dilator, ATP + ACh: 45 ± 9 vs. SNP + ACh: 18 ± 7 and ATP + SNP: 26 ± 4 mL·min-1·100 mmHg-1, P < 0.05). Phenylephrine was subsequently infused to evaluate α1-adrenergic vasoconstriction. Phenylephrine elicited less vasoconstriction during infusion of ATP or ACh versus SNP (ΔFVC, -25 ± 3 and -29 ± 4 vs. -48 ± 3%; P < 0.05). The vasoconstrictor response to phenylephrine was further diminished during combined infusion of ATP + ACh (-13 ± 3%; P < 0.05 vs. ATP or ACh alone) and was less than that observed when either dilator was combined with SNP (SNP + ACh: -26 ± 3%; ATP + SNP: -31 ± 4%; both P < 0.05 vs. ATP + ACh). We conclude that endothelium-dependent agonists interact to elicit vasodilation and limit α1-adrenergic vasoconstriction in humans.NEW & NOTEWORTHY The results of this study highlight the vascular endothelium as a critical site for integration of vasomotor signals in humans. To our knowledge, this is the first study to demonstrate that combined stimulation of the endothelium with ATP and ACh results in enhanced vasodilation compared with combination of either ATP or ACh with an endothelium-independent dilator. Furthermore, we show that ATP and ACh interact to modulate α1-adrenergic vasoconstriction in human skeletal muscle in vivo.


Assuntos
Acetilcolina , Vasoconstrição , Trifosfato de Adenosina , Adrenérgicos , Endotélio Vascular , Feminino , Antebraço , Humanos , Masculino , Nitroprussiato/farmacologia , Fluxo Sanguíneo Regional , Vasodilatação , Adulto Jovem
12.
Am J Physiol Heart Circ Physiol ; 321(2): H339-H352, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-34170194

RESUMO

Electronic cigarettes (E-cigs) have been promoted as harm-free or less risky than smoking, even for women during pregnancy. These claims are made largely on E-cig aerosol having fewer number of toxic chemicals compared with cigarette smoke. Given that even low levels of smoking are found to produce adverse birth outcomes, we sought to test the hypothesis that vaping during pregnancy (with or without nicotine) would not be harm-free and would result in vascular dysfunction that would be evident in offspring during adolescent and/or adult life. Pregnant female Sprague Dawley rats were exposed to E-cig aerosol (1 h/day, 5 days/wk, starting on gestational day 2 until pups were weaned) using e-liquid with 0 mg/mL (E-cig0) or 18 mg/mL nicotine (E-cig18) and compared with ambient air-exposed controls. Body mass at birth and at weaning were not different between groups. Assessment of middle cerebral artery (MCA) reactivity revealed a 51%-56% reduction in endothelial-dependent dilation response to acetylcholine (ACh) for both E-cig0 and E-cig18 in 1-mo, 3-mo (adolescent), and 7-mo-old (adult) offspring (P < 0.05 compared with air, all time points). MCA responses to sodium nitroprusside (SNP) and myogenic tone were not different across groups, suggesting that endothelial-independent responses were not altered. The MCA vasoconstrictor response (5-hydroxytryptamine, 5-HT) was also not different across treatment and age groups. These data demonstrate that maternal vaping during pregnancy is not harm-free and confers significant cerebrovascular health risk/dysfunction to offspring that persists into adult life. NEW & NOTEWORTHY These data established that vaping electronic cigarettes during pregnancy, with or without nicotine, is not safe and confers significant risk potential to the cerebrovascular health of offspring in early and adult life. A key finding is that vaping without nicotine does not protect offspring from cerebrovascular dysfunction and results in the same level of cerebrovascular dysfunction (compared with maternal vaping with nicotine), indicating that the physical and/or chemical properties from the base solution (other than nicotine) are responsible for the cerebrovascular dysfunction that we observed. Listen to this article's corresponding podcast at https://ajpheart.podbean.com/e/maternal-vaping-impairs-vascular-function-in-theoffspring/.


Assuntos
Vapor do Cigarro Eletrônico/farmacologia , Artéria Cerebral Média/efeitos dos fármacos , Nicotina/farmacologia , Agonistas Nicotínicos/farmacologia , Efeitos Tardios da Exposição Pré-Natal , Vaping , Vasoconstrição/efeitos dos fármacos , Vasodilatação/efeitos dos fármacos , Acetilcolina/farmacologia , Aerossóis , Animais , Sistemas Eletrônicos de Liberação de Nicotina , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/fisiopatologia , Feminino , Artéria Cerebral Média/fisiopatologia , Nicotina/administração & dosagem , Agonistas Nicotínicos/administração & dosagem , Nitroprussiato/farmacologia , Gravidez , Ratos , Serotonina/farmacologia , Vasoconstrição/fisiologia , Vasoconstritores/farmacologia , Vasodilatação/fisiologia , Vasodilatadores/farmacologia
13.
PLoS One ; 16(5): e0250486, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33975330

RESUMO

Research into the epigenome is of growing importance as a loss of epigenetic control has been implicated in the development of neurodegenerative diseases. Previous studies have implicated aberrant DNA and histone methylation in multiple sclerosis (MS) disease pathogenesis. We have previously reported that the methyl donor betaine is depleted in MS and is linked to changes in histone H3 trimethylation (H3K4me3) in neurons. We have also shown that betaine increases histone methyltransferase activity by activating chromatin bound betaine homocysteine S-methyltransferase (BHMT). Here, we investigated the role of the BHMT-betaine methylation pathway in oligodendrocytes. Immunocytochemistry in the human MO3.13 cell line, primary rat oligodendrocytes, and tissue from MS postmortem brain confirmed the presence of the BHMT enzyme in the nucleus in oligodendrocytes. BHMT expression is increased 2-fold following oxidative insult, and qRT-PCR demonstrated that betaine can promote an increase in expression of oligodendrocyte maturation genes SOX10 and NKX-2.2 under oxidative conditions. Chromatin fractionation provided evidence of a direct interaction of BHMT on chromatin and co-IP analysis indicates an interaction between BHMT and DNMT3a. Our data show that both histone and DNA methyltransferase activity are increased following betaine administration. Betaine effects were shown to be dependent on BHMT expression following siRNA knockdown of BHMT. This is the first report of BHMT expression in oligodendrocytes and suggests that betaine acts through BHMT to modulate histone and DNA methyltransferase activity on chromatin. These data suggest that methyl donor availability can impact epigenetic changes and maturation in oligodendrocytes.


Assuntos
Betaína-Homocisteína S-Metiltransferase/metabolismo , Betaína/metabolismo , Esclerose Múltipla/patologia , Oligodendroglia/efeitos dos fármacos , Animais , Betaína/farmacologia , Betaína-Homocisteína S-Metiltransferase/antagonistas & inibidores , Betaína-Homocisteína S-Metiltransferase/genética , Encéfalo/metabolismo , Encéfalo/patologia , Células Cultivadas , Cromatina/metabolismo , DNA (Citosina-5-)-Metiltransferases/metabolismo , Epigênese Genética , Expressão Gênica/efeitos dos fármacos , Histonas/metabolismo , Humanos , Metionina/metabolismo , Metilação , Esclerose Múltipla/genética , Nitroprussiato/farmacologia , Oligodendroglia/citologia , Oligodendroglia/metabolismo , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Ratos , Fatores de Transcrição SOXE/metabolismo
14.
Eur J Pharmacol ; 904: 174133, 2021 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-33984299

RESUMO

Angiotensin II-type 1 receptor stimulation is recognised to promote inflammation, a state central to the development and maintenance of rheumatoid arthritis. Herein we examined the use of losartan, an angiotensin II-type 1 receptor antagonist, on vascular reactivity, knee joint diameter and behavioural assessment of pain in a Freund's complete adjuvant (FCA) mouse model of joint inflammation. Monoarthritis was induced via FCA in the presence or absence of losartan with naive mice serving as controls. Knee joint swelling, joint pain (assessed by dynamic weight bearing of limb use), knee joint artery reactivity (assessed ex vivo) and blood perfusion of the knee joint (assessed in vivo) were determined. FCA mediated a significant increase in knee joint diameter and reduced weight-bearing (a surrogate for pain sensation) of the affected limb. Notably, these phenomena were substantially reduced when mice were prophylactically treated with losartan. Assessment of arterial relaxation and blood perfusion with acetylcholine stimulation revealed that FCA resulted in significant vascular dysfunction, which was resolved to naïve levels with losartan treatment. Through the actions of losartan, these findings indicate that the angiotensin II-type 1 receptor is a likely therapeutic target of importance in the development of the physical changes, pain sensation and vascular dysfunction found in inflammatory arthritis.


Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Artrite Experimental/tratamento farmacológico , Artrite Reumatoide/tratamento farmacológico , Losartan/farmacologia , Acetilcolina/farmacologia , Bloqueadores do Receptor Tipo 1 de Angiotensina II/administração & dosagem , Animais , Artérias/efeitos dos fármacos , Artralgia/induzido quimicamente , Artralgia/tratamento farmacológico , Circulação Sanguínea/efeitos dos fármacos , Citocinas/sangue , Adjuvante de Freund/toxicidade , Injeções Intraperitoneais , Articulação do Joelho/efeitos dos fármacos , Losartan/administração & dosagem , Masculino , Camundongos Endogâmicos C57BL , Nitroprussiato/farmacologia , Suporte de Carga
15.
Plant Physiol Biochem ; 162: 752-761, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33799186

RESUMO

In this study, the role of nitric oxide (NO) burst in modulating Si-induced defensive responses in leaves and roots of Salvia officinalis under copper (Cu) stress were investigated. The result showed that 400 µM Cu markedly reduced shoot dry weight, but increased electrolyte leakage (EL) in leaves and both Si and sodium nitroprusside (SNP as the NO donor) improved these attributes in a dose-dependent manner. Interestingly, Cu toxicity systemically boosted a NO burst in both roots and shoots and applying Si and SNP markedly intensified it. The application of Si and SNP alone as well as their combination improved growth parameters and systemically alleviated Cu-induced lipid peroxidation and H2O2 accumulation through lowering Cu accumulation, increasing proline content, enhancing the activities of catalase (CAT) and superoxide dismutase (SOD) in both roots and leaves and up-regulating expression of SOD gene in leaves of S. officinalis. NO generation was substantially arrested and the responses induced by Si were significantly suppressed by pretreatment with 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxy l-3-oxide (cPTIO) as a NO scavenger, Nx-Nitro- L-arginine methyl ester hydrochloride (L-NAME) as a nitric oxide synthase inhibitor, and tungstate as a nitrate reductase inhibitor. These novel results indicate that Si can induce Cu tolerance through triggering NO generation which systemically modulates defensive reactions in both roots and leaves of Salvia officinalis.


Assuntos
Óxido Nítrico , Salvia officinalis , Antioxidantes , Cobre/toxicidade , Peróxido de Hidrogênio , Nitroprussiato/farmacologia , Raízes de Plantas , Silício
16.
Molecules ; 26(9)2021 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-33925107

RESUMO

Soil salinity disrupts the physiological and biochemical processes of crop plants and ultimately leads to compromising future food security. Sodium nitroprusside (SNP), a contributor to nitric oxide (NO), holds the potential to alleviate abiotic stress effects and boost tolerance in plants, whereas less information is available on its role in salt-stressed lentils. We examined the effect of exogenously applied SNP on salt-stressed lentil plants by monitoring plant growth and yield-related attributes, biochemistry of enzymes (superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD)) amassing of leaf malondialdehyde (MDA) and hydrogen peroxide (H2O2). Salinity stress was induced by NaCl application at concentrations of 50 mM (moderate salinity) and 100 mM (severe salinity), while it was alleviated by SNP application at concentrations of 50 µM and 100 µM. Salinity stress severely inhibited the length of roots and shoots, the relative water content, and the chlorophyll content of the leaves, the number of branches, pods, seeds, seed yield, and biomass per plant. In addition, MDA, H2O2 as well as SOD, CAT, and POD activities were increased with increasing salinity levels. Plants supplemented with SNP (100 µM) showed a significant improvement in the growth- and yield-contributing parameters, especially in plants grown under moderate salinity (50 mM NaCl). Essentially, the application of 100 µM SNP remained effective to rescue lentil plants under moderate salinity by regulating plant growth and biochemical pathways. Thus, the exogenous application of SNP could be developed as a useful strategy for improving the performance of lentil plants in salinity-prone environments.


Assuntos
Lens (Planta)/efeitos dos fármacos , Lens (Planta)/fisiologia , Nitroprussiato/farmacologia , Desenvolvimento Vegetal/efeitos dos fármacos , Estresse Salino/efeitos dos fármacos , Antioxidantes/metabolismo , Peróxido de Hidrogênio/metabolismo , Lens (Planta)/química , Folhas de Planta/química , Folhas de Planta/efeitos dos fármacos , Folhas de Planta/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Estresse Fisiológico/efeitos dos fármacos
17.
ACS Appl Mater Interfaces ; 13(17): 19613-19624, 2021 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-33904311

RESUMO

Indwelling medical devices currently used to diagnose, monitor, and treat patients invariably suffer from two common clinical complications: broad-spectrum infections and device-induced thrombosis. Currently, infections are managed through antibiotic or antifungal treatment, but the emergence of antibiotic resistance, the formation of recalcitrant biofilms, and difficulty identifying culprit pathogens have made treatment increasingly challenging. Additionally, systemic anticoagulation has been used to manage device-induced thrombosis, but subsequent life-threatening bleeding events associated with all available therapies necessitates alternative solutions. In this study, a broad-spectrum antimicrobial, antithrombotic surface combining the incorporation of the nitric oxide (NO) donor S-nitroso-N-acetylpenicillamine (SNAP) with the immobilization of the antifungal Amphotericin B (AmB) on polydimethylsiloxane (PDMS) was developed in a two-step process. This novel strategy combines the key advantages of NO, a bactericidal agent and platelet inhibitor, with AmB, a potent antifungal agent. We demonstrated that SNAP-AmB surfaces significantly reduced the viability of adhered Staphylococcus aureus (99.0 ± 0.2%), Escherichia coli (89.7 ± 1.0%), and Candida albicans (93.5 ± 4.2%) compared to controls after 24 h of in vitro exposure. Moreover, SNAP-AmB surfaces reduced the number of platelets adhered by 74.6 ± 3.9% compared to controls after 2 h of in vitro porcine plasma exposure. Finally, a cytotoxicity assay validated that the materials did not present any cytotoxic side effects toward human fibroblast cells. This novel approach is the first to combine antifungal surface functionalization with NO-releasing technology, providing a promising step toward reducing the rate of broad-spectrum infection and thrombosis associated with indwelling medical devices.


Assuntos
Anfotericina B/uso terapêutico , Antifúngicos/uso terapêutico , Controle de Infecções/métodos , Óxido Nítrico/metabolismo , Trombose/prevenção & controle , Anfotericina B/administração & dosagem , Animais , Antifúngicos/administração & dosagem , Aderência Bacteriana/efeitos dos fármacos , Plaquetas/efeitos dos fármacos , Adesão Celular/efeitos dos fármacos , Humanos , Doadores de Óxido Nítrico/administração & dosagem , Nitroprussiato/administração & dosagem , Suínos
18.
PLoS One ; 16(4): e0248207, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33861749

RESUMO

Salinity is among the major abiotic stresses negatively affecting the growth and productivity of crop plants. Sodium nitroprusside (SNP) -an external nitric oxide (NO) donor- has been found effective to impart salinity tolerance to plants. Soybean (Glycine max L.) is widely cultivated around the world; however, salinity stress hampers its growth and productivity. Therefore, the current study evaluated the role of SNP in improving morphological, physiological and biochemical attributes of soybean under salinity stress. Data relating to biomass, chlorophyll and malondialdehyde (MDA) contents, activities of various antioxidant enzymes, ion content and ultrastructural analysis were collected. The SNP application ameliorated the negative effects of salinity stress to significant extent by regulating antioxidant mechanism. Root and shoot length, fresh and dry weight, chlorophyll contents, activities of various antioxidant enzymes, i.e., catalase (CAT), superoxide dismutase (SOD), peroxidase (POD) and ascorbate peroxidase (APX) were improved with SNP application under salinity stress compared to control treatment. Similarly, plants treated with SNP observed less damage to cell organelles of roots and leaves under salinity stress. The results revealed pivotal functions of SNP in salinity tolerance of soybean, including cell wall repair, sequestration of sodium ion in the vacuole and maintenance of normal chloroplasts with no swelling of thylakoids. Minor distortions of cell membrane and large number of starch grains indicates an increase in the photosynthetic activity. Therefore, SNP can be used as a regulator to improve the salinity tolerance of soybean in salt affected soils.


Assuntos
Nitroprussiato/farmacologia , Estresse Salino/fisiologia , Soja/metabolismo , Antioxidantes/metabolismo , Ascorbato Peroxidases/metabolismo , Clorofila/metabolismo , Malondialdeído/metabolismo , Nitroprussiato/metabolismo , Fotossíntese/efeitos dos fármacos , Folhas de Planta/metabolismo , Salinidade , Estresse Salino/efeitos dos fármacos , Tolerância ao Sal/efeitos dos fármacos , Tolerância ao Sal/fisiologia , Soja/crescimento & desenvolvimento , Estresse Fisiológico/efeitos dos fármacos , Superóxido Dismutase/metabolismo
19.
Microb Cell Fact ; 20(1): 92, 2021 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-33910564

RESUMO

BACKGROUND: Nitric oxide (NO) is a ubiquitous signaling mediator in various physiological processes. However, there are less reports concerning the effects of NO on fungal secondary metabolites. Hypocrellins are effective anticancer photodynamic therapy (PDT) agents from fungal perylenequinone pigments of Shiraia. NO donor sodium nitroprusside (SNP) was used as a chemical elicitor to promote hypocrellin biosynthesis in Shiraia mycelium cultures. RESULTS: SNP application at 0.01-0.20 mM was found to stimulate significantly fungal production of perylenequinones including hypocrellin A (HA) and elsinochrome A (EA). SNP application could not only enhance HA content by 178.96% in mycelia, but also stimulate its efflux to the medium. After 4 days of SNP application at 0.02 mM, the highest total production (110.34 mg/L) of HA was achieved without any growth suppression. SNP released NO in mycelia and acted as a pro-oxidant, thereby up-regulating the gene expression and activity of reactive oxygen species (ROS) generating NADPH oxidase (NOX) and antioxidant enzymes, leading to the increased levels of superoxide anion (O2-) and hydrogen peroxide (H2O2). Gene ontology (GO) analysis revealed that SNP treatment could up-regulate biosynthetic genes for hypocrellins and activate the transporter protein major facilitator superfamily (MFS) for the exudation. Moreover, SNP treatment increased the proportion of total unsaturated fatty acids in the hypha membranes and enhanced membrane permeability. Our results indicated both cellular biosynthesis of HA and its secretion could contribute to HA production induced by SNP. CONCLUSIONS: The results of this study provide a valuable strategy for large-scale hypocrellin production and can facilitate further understanding and exploration of NO signaling in the biosynthesis of the important fungal metabolites.


Assuntos
Ascomicetos/efeitos dos fármacos , Ascomicetos/genética , Vias Biossintéticas/genética , Doadores de Óxido Nítrico/farmacologia , Nitroprussiato/farmacologia , Perileno/análogos & derivados , Fenol/metabolismo , Quinonas/metabolismo , Transcrição Genética , Ascomicetos/metabolismo , Micélio/crescimento & desenvolvimento , Perileno/metabolismo , Espécies Reativas de Oxigênio
20.
Mol Biol Rep ; 48(3): 2243-2251, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33689094

RESUMO

Although nitric oxide (NO) is a key regulatory molecule in plants, its function in plants under conditions of simulated acid rain (SAR) has not been fully established yet. In this study, exogenous sodium nitroprusside (SNP) at three different concentrations were applied to mung bean seedlings. Malondialdehyde (MDA), NO, hydrogen peroxide (H2O2), antioxidant enzyme activities, and nitrate reductases (NR) were measured. Real time PCR was used to measure the NR expression. Compared to the control, the NR activity and NO content under the pH 2 SAR decreased by 79% and 85.6% respectively. Meanwhile, the SAR treatment reduced the activities of superoxide dismutase (SOD), peroxidase (POD), ascorbate peroxidase (APX), while increased MDA content. Application of SNP could potentially reverse the adverse impact of SAR, depending on its concentration. For plants under the pH 2 SAR and 0.25 mM SNP condition, the activities of SOD, POD, APX increased by 123%, 291%, and 135.7% respectively, meanwhile, MDA concentration decreased by 43%, NR activities increased by 269%, and NO concentration increased by 123.6% compared with plants undergoing only pH 2 SAR. The relative expression of the NR1 gene was 2.69 times higher than that of pH 2 SAR alone. Overall, the application of 0.25 mM SNP eliminated reactive oxygen species (ROS) by stimulating antioxidant enzyme activities, reducing oxidative stress and mitigating the toxic effects of SAR on mung bean seedlings. This research provides a foundation for further research on the mechanism of NO on plants under SAR conditions.


Assuntos
Chuva Ácida , Óxido Nítrico/farmacologia , Plântula/fisiologia , Estresse Fisiológico/efeitos dos fármacos , Vigna/fisiologia , Antioxidantes/metabolismo , Catalase/metabolismo , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Peróxido de Hidrogênio/metabolismo , Malondialdeído/metabolismo , Nitrato Redutase/genética , Nitrato Redutase/metabolismo , Nitroprussiato/farmacologia , Folhas de Planta/efeitos dos fármacos , Plântula/efeitos dos fármacos , Estresse Fisiológico/genética , Vigna/efeitos dos fármacos , Vigna/genética
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