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1.
Nutr Neurosci ; 25(10): 2077-2091, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34057051

RESUMEN

BACKGROUND: This study investigated the modulatory capacity of two Solanum green leafy vegetables; S. macrocarpon L. (African eggplant AE) and S. nigrum L. (Black nightshade BN) on dysregulation of some antioxidant, pro-apoptotic, pro-inflammatory-like, acetylcholinesterase gene expression and redox status in the Drosophila melanogaster model of aluminum-induced neurotoxicity. METHODS: Flies were exposed to AlCl3 (6.7 mM) alone or in combination with the leaves (0.1 and 1.0%) from both samples in their diet for seven days. Thereafter, the fly heads were rapidly separated, homogenized, and used to assay for reactive oxygen species (ROS), total thiol content, catalase, glutathione-S-transferase (GST), acetylcholinesterase (AChE) activities, and the expression of antioxidant-mediators (Hsp70, catalase, cnc/Nrf2, Jafrac1 and FOXO), acetylcholinesterase (Ace1), pro-apoptotic caspase-like (Dronc) and its regulator (reaper), as well as inflammation-related (NF-kB/Relish) genes. RESULTS: Results showed that AlCl3-exposed flies had significantly reduced survival rate which were ameliorated by AlCl3 also elevated ROS, GST and reduced AChE activities in fly heads while dietary inclusions of AE and BN ameliorated survial rate and oxidative stress in AlCl3-exposed flies. In addition, Hsp70, Jafrac1, reaper and NF-kҝB/Relish were significantly upregulated in AlCl3-exposed fly heads, while cnc/Nrf2 and FOXO were significantly downregulated, but catalase, Dronc and Ace were, not significantly modulated. Nevertheless, these impairments in gene expression levels were ameliorated by dietary inclusions of AE and BN during AlCl3 exposure. CONCLUSION: These findings showed that dietary inclusions of AE and BN leaves offer protection against Al-induced neurotoxicity in D. melanogaster and thus, could serve as functional foods with neuroprotective properties.


Asunto(s)
Síndromes de Neurotoxicidad , Solanum nigrum , Solanum , Acetilcolinesterasa/metabolismo , Aluminio/metabolismo , Animales , Antioxidantes/metabolismo , Caspasas/genética , Caspasas/metabolismo , Catalasa/genética , Catalasa/metabolismo , Dieta , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Glutatión/metabolismo , Glutatión Transferasa/metabolismo , Inflamación/inducido químicamente , Inflamación/prevención & control , Factor 2 Relacionado con NF-E2/metabolismo , FN-kappa B/metabolismo , Síndromes de Neurotoxicidad/etiología , Síndromes de Neurotoxicidad/metabolismo , Síndromes de Neurotoxicidad/prevención & control , Oxidación-Reducción , Estrés Oxidativo , Especies Reactivas de Oxígeno/metabolismo , Solanum/metabolismo , Solanum nigrum/metabolismo , Compuestos de Sulfhidrilo/metabolismo , Verduras
2.
Metab Brain Dis ; 37(3): 729-741, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-34994925

RESUMEN

African eggplant (Solanum macrocarpon L) (AE) and Black Nightshade (Solanum nigrum L) (BN) leaves are green leafy vegetables with nutritional and ethnobotanical values. We have previously characterized the vegetables via HPLC/LC-MS to reveal notable phenolic acids, flavonoids and alkaloids. In this present study, we addressed the efficacy of the two vegetables in mitigating mercuric chloride (HgCl2)-induced neurotoxicity and memory impairment in Drosophila melanogaster. Flies were exposed to HgCl2 (0.30 mg/g) alone or in combination with the vegetables (0.1 and 1.0%) of both samples in their diets for seven days. The results showed that HgCl2 (Hg)-exposed flies had significantly reduced survival rate and memory index, which were ameliorated in the Hg-exposed flies fed AE or BN. This was accompanied by increased reactive oxygen species (ROS) levels, reduced total thiol, as well as catalase, glutathione transferase (GST) and acetylcholine esterase (AChE) activities in Hg-exposed fly heads, but ameliorated in Hg-exposed flies fed dietary inclusions of the vegetables. In addition, the Hg-induced alterations in SOD, NF-ҝB/Relish, Dronc and Reaper mRNA levels were statistically indistinguishable from controls in Hg-treated flies fed diets containing AE or BN. Normalization of cnc/Nrf2 and FOXO were observed only in Hg-treated flies fed BN. These findings suggest that dietary AE or BN leaves offer protection against Hg-induced memory impairment and neurotoxicity in D. melanogaster, and further justify them as functional foods with neuroprotective properties.


Asunto(s)
Solanum nigrum , Solanum , Animales , Antioxidantes/farmacología , Drosophila melanogaster , Oxidación-Reducción , Estrés Oxidativo , Verduras
3.
Chem Biodivers ; 19(5): e202100793, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-35293125

RESUMEN

The present study reports a simple two-step method for the synthesis of arylselanyl hydrazide derivatives using hypophosphorous acid and polyethylene glycol (H3 PO2 /PEG-400) as an alternative reducing system and hydrazine hydrate (NH2 NH2 ⋅xH2 O/50-60 %). This single-vessel procedure was employed with methyl acrylate 2a and methyl bromoacetate 2b using diaryl diselenides to generate the nucleophile species to produce, respectively, 3-(arylselanyl)propane-hydrazides 4a-e and 2-(arylselanyl)acetohydrazides 5a-e with good yields by accelerating the reduction of -Se-Se- bond, when compared to available methods. The synthesized molecules are structurally similar to the isoniazid (INH). Therefore, we perform in silico molecular docking studies, using the lactoperoxidase enzyme, in order to verify whether the INH Se derivatives could interact in a similar way to INH at the active site of the mammalian enzyme. The in silico results indicated a similar type of interaction of the arylselanyl hydrazide derivatives with that of INH. In view of the similar in silico interaction of the selenium derivatives of INH, the arylselanyl hydrazide derivatives reported here should be tested against Mycobacterium tuberculosis in vitro.


Asunto(s)
Antituberculosos , Mycobacterium tuberculosis , Animales , Hidrazinas , Isoniazida/química , Isoniazida/farmacología , Mamíferos , Simulación del Acoplamiento Molecular
4.
Environ Res ; 177: 108637, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-31416010

RESUMEN

Climate change is one of the biggest and most urgent challenges for the 21st century. Rising average temperatures and ocean levels, altered precipitation patterns and increased occurrence of extreme weather events affect not only the global landscape and ecosystem, but also human health. Multiple environmental factors influence the onset and severity of human diseases and changing climate may have a great impact on these factors. Climate shifts disrupt the quantity and quality of water, increase environmental pollution, change the distribution of pathogens and severely impacts food production - all of which are important regarding public health. This paper focuses on brain health and provides an overview of climate change impacts on risk factors specific to brain diseases and disorders. We also discuss emerging hazards in brain health due to mitigation and adaptation strategies in response to climate changes.


Asunto(s)
Encefalopatías/epidemiología , Cambio Climático , Exposición a Riesgos Ambientales/estadística & datos numéricos , Ecosistema , Contaminación Ambiental/estadística & datos numéricos , Humanos , Salud Pública
5.
Pak J Pharm Sci ; 29(2): 615-21, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-27087084

RESUMEN

The present study was designed to investigate the mineral content and antimicrobial activity of Curcuma Longa extracts and its essential oil. We also determined the lipid peroxidation inhibition activity of the ethanolic extract against sodium nitroprusside (SNP) induced thiobarbituric acid reactive species (TBARS) formation in rat's brain, kidney and liver homogenates. Major constituents of essential oil identified by gas chromatography and mass spectrometry (GCMS) were beta-sesquiphellandrene (38.69%), alpha-curcumene (18.44%) and p-mentha-1,4 (8)-diene (16.29%). Atomic absorption spectroscopy (AAS) was used for the quantitative estimation of Calcium (Ca), Magnesium (Mg), Iron (Fe), Copper (Cu), Zinc (Zn), Chromium (Cr), Nickel (Ni) and Manganese (Mn). The extract showed highest Mg (49.4 mg/l) concentration followed by Ca (35.42 mg/l) and Fe (1.27 mg/l). Our data revealed that the ethanolic extract of Curcuma Longa at 1-10 mg/kg significantly inhibited TBARS production in all tested homogenates. Crude extracts and essential oil were tested against three gram positive bacteria i.e. Bacillus subtilis, Bacillus atrophoeus, Staphylococcus aureus, six gram negative bacteria i.e. Escherichia coli, Klebsiella pneumonias, Salmonella typhi, Pseudomonas aeruginosa, Erwinia carotovora, Agrobacterium tumefaciens and one fungal strain namely Candida albicans by disc diffusion assay. Essential oil showed highest anti-microbial activity as compared to the crude extracts. The present study confirms the significant antimicrobial and antioxidant potential of the studied plant, which can be considered as a diet supplement for a variety of oxidative stress induced or infectious diseases.


Asunto(s)
Antiinfecciosos/farmacología , Antioxidantes/farmacología , Curcuma/química , Cromatografía de Gases y Espectrometría de Masas , Peroxidación de Lípido/efectos de los fármacos , Aceites Volátiles/farmacología , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/farmacología , Aceites de Plantas/farmacología , Antiinfecciosos/aislamiento & purificación , Antioxidantes/aislamiento & purificación , Bacterias/efectos de los fármacos , Bacterias/crecimiento & desarrollo , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Candida albicans/efectos de los fármacos , Candida albicans/crecimiento & desarrollo , Pruebas Antimicrobianas de Difusión por Disco , Relación Dosis-Respuesta a Droga , Etanol/química , Riñón/efectos de los fármacos , Riñón/metabolismo , Hígado/efectos de los fármacos , Hígado/metabolismo , Malondialdehído/metabolismo , Nitroprusiato/farmacología , Aceites Volátiles/aislamiento & purificación , Fitoterapia , Extractos Vegetales/aislamiento & purificación , Aceites de Plantas/aislamiento & purificación , Plantas Medicinales , Solventes/química , Espectrofotometría Atómica , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismo
6.
Pak J Pharm Sci ; 29(1): 231-7, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26826815

RESUMEN

The study describes the effect of ethanolic extract of Nigella sativa against Fe(II) induced lipid peroxidation. Basal and Fe(II) induced thiobarbituric acid reactive species (TBARS) production was significantly inhibited by the ethanolic extract of Nigella sativa at 25-200 µg/ml. Our data revealed that the extract has high DPPH radical scavenging activity at highest tested concentrations. The extract significantly chelated Fe(II) and scavenged hydroxyl (OH) radical at 25-200µg/ml concentration. The nutritional analysis was performed and carbohydrate, fats, fiber, protein, moisture and ash content were measured in the studied extract. The phytochemical analysis confirmed the presence of alkaloid, carbohydrate & sugar, glycosides, phenolic compounds, flavonoids, protein and amino acid, phytosterols, tannins, gum and mucilage. The extract also showed significant antimicrobial activities against 10 bacterial strains i.e. Salmonella typhi, Bacillus subtilis, Bacillus cereus, Klebsiella pneumonia, Escheria coli, Xanthomonas, Salmonella heidelberg, Staphylococcus aureus, Clostridium and Escheria coli (human) and 5 fungal strains i.e. Aspergillus niger, Entomola, Aspergillus flavus, Alternaria alternata and Penicillium. This study confirms the potential antioxidant and antimicrobial activities of ethanolic extract of Nigella sativa which can be considered not only as a diet supplement but can be used against a variety of free radical induced damage diseases.


Asunto(s)
Encéfalo/efectos de los fármacos , Riñón/efectos de los fármacos , Peroxidación de Lípido/efectos de los fármacos , Hígado/efectos de los fármacos , Nigella sativa/química , Extractos Vegetales/farmacología , Animales , Encéfalo/metabolismo , Etanol , Riñón/metabolismo , Hígado/metabolismo , Masculino , Ratas , Ratas Wistar
7.
Cell Biol Int ; 38(5): 625-30, 2014 May.
Artículo en Inglés | MEDLINE | ID: mdl-24470283

RESUMEN

Diabetic status is associated with an increase on oxidative stress markers in humans and animal models. We have investigated the in vitro effects of high concentrations of glucose on the profile of oxidative stress and osmotic fragility of blood from control and diabetic patients; we considered whether its antioxidant properties could afford some protection against glucose-induced osmotic fragility, and whether ebselen could act as an inhibitor of hemoglobin glycation. Raising blood glucose to 5-100 mmol/L resulted in a concentration-dependent increase of glycated hemoglobin (HbA1c; P < 0.001) and thiobarbituric acid reactive species (TBA-RS) content (P < 0.004). Non-protein SH groups (NPSH) also increased significantly as the concentration of glucose increased up to 30 mmol/L (P < 0.001). The osmotic fragility was more pronounced in blood of uncontrolled diabetic patients than in these non-diabetic subjects. Ebselen significantly reduced the glucose-induced increase in osmotic fragility and inhibited HbA1c formation (P < 0.0001). These results indicate that blood from patients with uncontrolled diabetes are more sensitive to osmotic shock than from patients with controlled diabetes and control subjects in relation to increased production of free radicals in vivo.


Asunto(s)
Antioxidantes/farmacología , Azoles/farmacología , Eritrocitos/efectos de los fármacos , Eritrocitos/metabolismo , Glucosa/toxicidad , Compuestos de Organoselenio/farmacología , Diabetes Mellitus Tipo 2/sangre , Glicosilación/efectos de los fármacos , Humanos , Isoindoles , Fragilidad Osmótica/efectos de los fármacos , Fragilidad Osmótica/fisiología
8.
Diabetes Metab Syndr ; 17(4): 102760, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37084485

RESUMEN

BACKGROUND AND AIMS: In the present study the research output of the South Asian region (India, Pakistan, Bangladesh, Sri Lanka, Nepal, Maldives, and Bhutan) in endocrinology, diabetes and metabolism (EDM) is highlighted. It was compared with five scientifically advanced countries i.e. USA, UK, Italy, Japan and China. METHODS: On September 13, 2022, the data was retrieved from the Scopus database. The analysis focused on the number of publications, total citations (TC), citations per paper (CPP), field-weighted citations impact (FWCI), and degree of international collaboration. RESULTS: In South Asia, India produced the highest number of publications (n = 7048), followed by Pakistan (n = 799), Bangladesh (n = 345), Sri Lanka (n = 256), Nepal (n = 144), Maldives (n = 12) and Bhutan (n = 4). The highest CPP (n = 19.4) and FWCI (n = 1.18) was recorded for Sri Lanka. Furthermore, USA (n = 64022), China (n = 23991), UK (n = 21449), Italy (n = 18884), and Japan (n = 12875), published the highest number of documents with the highest citations and FWCI in the world. It was noted that India published the highest number of documents (n = 47.28%) in the quartiles (Q) 6 and Q7. Pakistan produced the highest number of documents (n = 64.22%) in the top 50% of journals (Q1 to Q5). South Asian countries produced 8332 publications, with 130382 TC, 15.6 CPP and 1.06 FWCI. Importantly 46.50% of documents from South Asian countries were published in Q6 and Q7 journals. In contrast USA, UK, Italy, Japan and China published 77% documents in top 50% journals. CONCLUSIONS: Although the South Asian research publications have increased yearly (from 2012 to 2021), but approximately 50% of the South Asian output were in the lower quartile journals. Consequently, significant measures are needed to improve the quantity and quality of EDM research produced in South Asian coutries.


Asunto(s)
Bibliometría , Diabetes Mellitus , Humanos , Sur de Asia , Países Desarrollados , India , Diabetes Mellitus/epidemiología
9.
Data Brief ; 28: 104986, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32462060

RESUMEN

This article presents the statistical analysis data from Drosophila melanogaster development (from larvae to adult) and learning and memory retention behavior of a Pavlovian conditioning in male and female flies exposed to copper. While the full data sets are available In the article: Copper decrease associative learning and memory in D. melanogaster, this data-in-brief article includes the detailed statistical analysis performed. Data demonstrates Statistica Software analysis between the subject part of the analysis: 2 treatments x 2 sexes x 2 ages and within subject part of the analysis: 2 treatments x 2 sex x 2 ages x 4 times, repeated measures.

11.
J Ethnopharmacol ; 210: 69-79, 2018 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-28844679

RESUMEN

ETNOPHARMACOLOGICAL RELEVANCE: Syzygium cumini (L.) Skeels is a plant widely used in folk medicine to treat diabetes mellitus (DM). The tea from its leaves is frequently used by diabetics for lowering hyperglycemia. There is a close relationship between DM and atherosclerosis, a chronic immuno-inflammatory disease, were the early stages encompass oxidative and glycative modifications in the structure of low density lipoprotein (LDL). AIM OF THIS STUDY: To investigate the potential protective effects of aqueous-leaf extract from Syzygium cumini (S.cExt) against CuSO4-induced oxidation and methylglyoxal (MG)-induced glycation of human LDL in vitro. MATERIALS AND METHODS: LDL oxidative changes were evaluated by measuring conjugated dienes (CD) formation, thiobarbituric acid reactive substances (TBARS) levels, quenching of tryptophan (Trp) fluorescence and structural modifications in LDL particle. In LDL glycated by MG (glyLDL), we determined the levels of fluorescent advanced glycation end products (AGEs) and mobility by agarose gel electrophoresis. RESULTS: S.cExt blocked oxidative events induced by CuSO4 in human LDL, plasma and serum. Fourier transform infrared spectroscopy (FT-IR) revealed that specific regions of apoB100 were oxidized by CuSO4 in human LDL and that S.cExt reduced these oxidations. Unlike, the increased AGEs levels and eletrophoretic mobility observed in LDL MG-glycated were not modified by S.cExt. CONCLUSION: The findings herein indicate that S.cExt could be tested in atherogenesis models as potential protective agent against LDL oxidation.


Asunto(s)
Lipoproteínas LDL/metabolismo , Extractos Vegetales/farmacología , Syzygium/química , Apolipoproteína B-100/metabolismo , Sulfato de Cobre/administración & dosificación , Electroforesis en Gel de Agar , Productos Finales de Glicación Avanzada/metabolismo , Humanos , Medicina Tradicional , Oxidación-Reducción , Hojas de la Planta , Espectroscopía Infrarroja por Transformada de Fourier , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismo
12.
Curr Top Med Chem ; 17(12): 1336-1370, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28049396

RESUMEN

Reactive species are produced in biological system because of redox reactions. The imbalance in pro-oxidant and antioxidant homeostasis leads to the production of toxic reactive oxygen and nitrogen species like hydrogen peroxide, organic peroxides, hydroxyl radicals, superoxide anion and nitric oxide. Inactivation of metabolic enzymes, oxidation of biomolecules and cellular damage are some of the prominent characteristics of reactive species. Similarly, oxidative stress has been associated with more than one hundred (100) pathologies such as atherosclerosis, diabetes, cardiovascular diseases, pancreatic and liver diseases, joint disorders, cardiac fibrosis, acute respiratory distress syndrome, neurological diseases (amyotrophic lateral sclerosis, Huntington's disorder, Parkinson's disease and Alzheimer's disease), ageing and cancer etc. The toxicity of reactive species is balanced by the integrated antioxidant systems, which include enzymatic and non-enzymatic antioxidants. Antioxidant therapies or defenses protect the biological sites by removing or quenching the free radicals (prooxidants). Medicinal plants can not only protect the oxidative damage, but also play a vital role in health maintenance and prevention of chronic degenerative diseases. This review will provide a valuable discussion of one hundred (100) well known medicinal plants, which may add to the optimization of antioxidants rank. Besides, some of the antioxidant evaluation techniques or mechanisms via which medicinal plants act as antioxidants are also described.


Asunto(s)
Antioxidantes/farmacología , Estrés Oxidativo/efectos de los fármacos , Plantas Medicinales/química , Antioxidantes/química , Humanos , Especies de Nitrógeno Reactivo/antagonistas & inhibidores , Especies de Nitrógeno Reactivo/metabolismo , Especies Reactivas de Oxígeno/antagonistas & inhibidores , Especies Reactivas de Oxígeno/metabolismo
13.
Environ Toxicol Pharmacol ; 36(3): 813-8, 2013 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-23958975

RESUMEN

In this study we have examined the in vivo toxic effects of various organochalcogens on hepatic, renal, glycemic and lipid profile. Diorganotellurium dichloride phosphonate (C1) at all tested doses did not modify serum alanine aminotransferase (ALT) activity in mice. While, 2-butyltellurium furan (C2) and dinaphthalene ditelluride (C3) at a dose of 0.75 and 0.125 mmol/kg caused an increase in aspartate aminotransferase (AST) and ALT activities. Our data showed that C1 caused an increase in urea content at different doses while treatment with C2 and C3 did not modify urea content. Treatment with C2 caused a significant alteration in serum glucose and fructosamine levels which explains the possible toxicity of these compounds. No significant changes were observed for cholesterol and triglycerides levels. These results suggest that organochalcogen compounds presented liver and renal toxicity and also altered glycemic profile which may leads to various clinical complications.


Asunto(s)
Compuestos Organometálicos/toxicidad , Telurio/toxicidad , Alanina Transaminasa/sangre , Animales , Aspartato Aminotransferasas/sangre , Glucemia/metabolismo , Nitrógeno de la Urea Sanguínea , Cromatografía de Gases , Cromatografía Líquida de Alta Presión , Creatinina/sangre , Relación Dosis-Respuesta a Droga , Fructosamina/sangre , Hemoglobinas/metabolismo , Pruebas de Función Renal , Lípidos/sangre , Pruebas de Función Hepática , Espectroscopía de Resonancia Magnética , Masculino , Ratones , Análisis de Supervivencia
14.
Pathol Res Pract ; 207(9): 554-8, 2011 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-21856092

RESUMEN

Sepsis is a potentially deadly complication that can be caused by different factors. Actually, it is known that oxidative stress is involved in the pathogenesis of sepsis. Thus, the aim of this study was to evaluate the effect of diphenyl diselenide (PhSe)(2), an emergent compound, on oxidative stress parameters induced by sepsis in rats. Animals were pre-injected with (PhSe)(2) or vehicle. Twenty-four hours later, sepsis was induced by cecal ligation puncture (CLP). After 12 h, liver was taken for thiobarbituric acid reactive species (TBARS) measurement, δ-aminolevunic acid dehydratase (δ-ALA-D), Cu/Zn superoxide dismutase (Cu/Zn SOD) and catalase (CAT) activities assay. The sepsis increased TBARS, inhibited δ-ALA-D, activated Cu/Zn SOD and had a tendency to decrease CAT activity. However, (PhSe)(2) prevented the TBARS formation, but did not prevent the inhibition of δ-ALA-D activity in the animals with damage. Thus, this study showed that (PhSe)(2) partially prevents the oxidative stress induced by sepsis, indicating the potential of this compound as a treatment for this pathology. Nevertheless, more tests should be performed to confirm the hypothesis suggested here.


Asunto(s)
Antioxidantes/farmacología , Derivados del Benceno/farmacología , Compuestos de Organoselenio/farmacología , Estrés Oxidativo/efectos de los fármacos , Sepsis/tratamiento farmacológico , Animales , Catalasa/metabolismo , Ciego/lesiones , Modelos Animales de Enfermedad , Ligadura , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Porfobilinógeno Sintasa/metabolismo , Ratas , Ratas Wistar , Sepsis/metabolismo , Sepsis/patología , Superóxido Dismutasa/metabolismo , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismo
16.
Anesth Analg ; 101(1): 115-20, table of contents, 2005 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-15976216

RESUMEN

Acute pulmonary embolism (APE) is a major cause of pulmonary hypertension and death. We examined the effects of sildenafil on the hemodynamic changes caused by APE in anesthetized dogs. Sham-operated dogs (n = 3) received only saline. APE was induced by stepwise IV injections of 300 mum microspheres in amounts adjusted to increase mean pulmonary artery pressures by 20 mm Hg. Hemodynamic evaluation was performed at baseline, after APE was induced, and then after sildenafil 0.25 mg/kg (n = 8), or sildenafil 1 mg/kg + 0.3 mg . kg(-1) . h(-1) (n = 8) or saline (n = 9) infusions were started. Similar experiments were conducted to examine the effects of sildenafil in rat isolated perfused lung preparation. Plasma thiobarbituric acid reactive species were also determined in both studies to measure oxidative stress. Both doses of sildenafil reduced mean pulmonary artery pressures in dogs by approximately 8 to 16 mm Hg (both P < 0.05) and attenuated the increase in oxidative stress after APE. Mean arterial blood pressure remained unaltered after both doses of sildenafil. Sildenafil produced similar effects after APE in rat isolated perfused lung preparation. These findings indicate that IV sildenafil can selectively attenuate the increases in mean pulmonary artery pressures after APE, possibly through antioxidant mechanisms.


Asunto(s)
Hipertensión Pulmonar/fisiopatología , Estrés Oxidativo/efectos de los fármacos , Inhibidores de Fosfodiesterasa/farmacología , Piperazinas/farmacología , Embolia Pulmonar/complicaciones , Vasodilatadores/farmacología , Enfermedad Aguda , Animales , Presión Sanguínea/efectos de los fármacos , Perros , Femenino , Hemodinámica/efectos de los fármacos , Hipertensión Pulmonar/etiología , Masculino , Malondialdehído/sangre , Arteria Pulmonar/fisiología , Embolia Pulmonar/metabolismo , Embolia Pulmonar/fisiopatología , Purinas , Ratas , Ratas Wistar , Citrato de Sildenafil , Sulfonas , Sustancias Reactivas al Ácido Tiobarbitúrico
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