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1.
Life Sci ; 351: 122819, 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-38857651

ABSTRACT

AIMS: Our aim was to evaluate whether the hydrogen sulfide (H2S) donor, 4-carboxyphenyl-isothiocyanate (4-CPI), exerts cardioprotective effect in the two kidney- one clip (2K-1C) rats through oxidative stress and MMP-2 activity attenuation and compare it with the classical H2S donor, Sodium Hydrosulfide (NaHS). MATERIALS AND METHODS: Renovascular hypertension (two kidneys-one clip; 2K-1C) was surgically induced in male Wistar rats. After two weeks, normotensive (2K) and hypertensive rats were intraperitoneally treated with vehicle (0.6 % dimethyl sulfoxide), NaHS (0.24 mg/Kg/day) or with 4-CPI (0.24 mg/Kg/day), for more 4 weeks. Systolic blood pressure (SBP) was evaluated weekly by tail-cuff plethysmography. Heart function was assessed by using the Millar catheter. Cardiac hypertrophy and fibrosis were evaluated by hematoxylin and eosin, and Picrosirius Red staining, respectively. The H2S was analyzed using WSP-1 fluorimetry and the cardiac oxidative stress was measured by lucigenin chemiluminescence and Amplex Red. MMP-2 activity was measured by in-gel gelatin or in situ zymography assays. Nox1, gp91phox, MMP-2 and the phospho-p65 subunit (Serine 279) nuclear factor kappa B (NF-κB) levels were evaluated by Western blotting. KEY FINDINGS: 4-CPI reduced blood pressure in hypertensive rats, decreased cardiac remodeling and promoted cardioprotection through the enhancement of cardiac H2S levels. An attenuation of oxidative stress, with inactivation of the p65-NF-κB/MMP-2 axis was similarly observed after NaHS or 4-CPI treatment in 2K-1C hypertension. SIGNIFICANCE: H2S is a mediator that promotes cardioprotective effects and decreases blood pressure, and 4-CPI seems to be a good candidate to reverse the maladaptive remodeling and cardiac dysfunction in renovascular hypertension.


Subject(s)
Blood Pressure , Hydrogen Sulfide , Matrix Metalloproteinase 2 , NF-kappa B , Oxidative Stress , Animals , Male , Rats , Blood Pressure/drug effects , Cardiotonic Agents/pharmacology , Hydrogen Sulfide/pharmacology , Hydrogen Sulfide/metabolism , Hypertension/drug therapy , Hypertension/metabolism , Hypertension, Renovascular/drug therapy , Hypertension, Renovascular/metabolism , Hypertension, Renovascular/physiopathology , Isothiocyanates/pharmacology , Matrix Metalloproteinase 2/metabolism , NF-kappa B/metabolism , Oxidative Stress/drug effects , Rats, Wistar , Sulfides/pharmacology
2.
Antioxid Redox Signal ; 40(4-6): 250-271, 2024 02.
Article in English | MEDLINE | ID: mdl-37597204

ABSTRACT

Significance: Cancer is a complex and heterotypic structure with a spatial organization that contributes to challenges in therapeutics. Enzymes associated with producing the gasotransmitter hydrogen sulfide (H2S) are differentially expressed in tumors. Indeed, critical and paradoxical roles have been attributed to H2S in cancer-promoting characteristics by targeting both cancer cells and their milieu. This review focuses on the evidence and knowledge gaps of H2S on the tumor redox microenvironment and the pharmacological effects of H2S donors on cancer biology. Recent Advances: Endogenous and pharmacological concentrations of H2S evoke different effects on the same cell type: physiological H2S concentrations have been associated with tumor development and progression. In contrast, pharmacological concentrations have been associated with anticancer effects. Critical Issues: The exact threshold between the promotion and inhibition of tumorigenesis by H2S is largely unknown. The main issues covered in this review include H2S-modulated signaling pathways that are critical for cancer cells, the potential effects of H2S on cellular components of the tumor microenvironment, temporal modulation of H2S in promoting or inhibiting tumor progression (similar to observed for inflammation), and pharmacological agents that modulate H2S and which could play a role in antineoplastic therapy. Future Directions: Given the complexity and heterogeneity of tumor composition, mechanistic studies on context-dependent pharmacological effects of H2S donors for cancer therapy are necessary. These studies must determine the critical signaling pathways and the cellular components involved to allow advances in the rational use of H2S donors as antineoplastic agents. Antioxid. Redox Signal. 40, 250-271.


Subject(s)
Gasotransmitters , Hydrogen Sulfide , Neoplasms , Humans , Hydrogen Sulfide/metabolism , Neoplasms/drug therapy , Neoplasms/metabolism , Gasotransmitters/metabolism , Signal Transduction , Carcinogenesis , Tumor Microenvironment
3.
Molecules ; 28(18)2023 Sep 16.
Article in English | MEDLINE | ID: mdl-37764431

ABSTRACT

The present study employs high-level ab initio calculations to investigate the structure, vibrational frequencies, and electronic properties of H2S∙∙∙SO2. The analysis of vibrational frequencies reveals an intramolecular vibrational energy transfer phenomenon, where energy from the stretching modes of H2S is transferred to the ν1s mode of SO2. At the CCSD(T)/aug-cc-pVQZ level, the interaction energy between H2S and SO2 is predicted to be 2.78 kcal/mol. Electron propagator theory calculations yield a HOMO-LUMO gap of 8.24 eV for H2S∙∙∙SO2. Furthermore, by utilizing ab initio results for the adiabatic ionization energy and electron affinity, the electrophilicity of H2S∙∙∙SO2 is estimated to be 2.01 eV. This value is similar to the electrophilicity of SO2, suggesting comparable reactivity and chemical behavior. The non-covalent interaction (NCI) analysis of the H2S∙∙∙SO2 complex emphasizes the significant contribution of non-covalent van der Waals interactions in its energetic stabilization.

4.
Eur J Pharmacol ; 938: 175409, 2023 Jan 05.
Article in English | MEDLINE | ID: mdl-36436591

ABSTRACT

Hydrogen sulfide (H2S) is a gaseous mediator that modulates several physiological and pathological processes. Phthalimide analogues, substances that have the phthalimide ring in the structure, belong to the group of thalidomide analogues. Both H2S donors and phthalimide analogues exhibit activities in models of inflammation and pain. As molecular hybridization is an important strategy aiming to develop drugs with a better pharmacological profile, in the present study we synthesized a novel H2S-releasing phthalimide hybrid, 2-(2-(4-thioxo-3H-1,2-dithiole-5-yl) phenoxy)ethyl)isoindole-1,3-thione (PTD-H2S), and evaluated its activity in models of inflammatory pain in mice. Per os (p.o.) administration of PTD-H2S (125 or 250 mg/kg) reduced mechanical allodynia induced by carrageenan and lipopolysaccharide. Intraperitoneal (i.p.) administration of PTD-H2S (25 mg/kg), but not equimolar doses of its precursors 5-(4-hydroxyphenyl)-3H-1,2-dithiole-3-thione (14.2 mg/kg) and 2-phthalimidethanol (12 mg/kg), reduced mechanical allodynia induced by lipopolysaccharide. The antiallodynic effect induced by PTD-H2S (25 mg/kg, i.p.) was more sustained than that induced by the H2S donor NaHS (8 mg/kg, i.p.). Previous administration of hydroxocobalamin (300 mg/kg, i.p.) or glibenclamide (40 mg/kg, p.o.) attenuated PTD-H2S antiallodynic activity. In conclusion, we synthesized a novel H2S-releasing phthalimide hybrid and demonstrated its activity in models of inflammatory pain. PTD-H2S activity may be due to H2S release and activation of ATP-sensitive potassium channels. The demonstration of PTD-H2S activity in models of pain stimulates further studies aiming to evaluate H2S-releasing phthalimide hybrids as candidates for analgesic drugs.


Subject(s)
Hydrogen Sulfide , Hyperalgesia , Mice , Animals , Thiones , Isoindoles , Lipopolysaccharides , Pain/drug therapy , Phthalimides/pharmacology , Phthalimides/therapeutic use , Phthalimides/chemistry
5.
Life Sci ; 312: 121218, 2023 Jan 01.
Article in English | MEDLINE | ID: mdl-36427545

ABSTRACT

AIM: To assess the effects of subchronic administration with NaHS, an exogenous H2S donor, on TBI-induced hypertension and vascular impairments. MAIN METHODS: Animals underweministration does not prevent the body weight loss but slightly imnt a lateral fluid percussion injury, and the hemodynamic variables were measured in vivo by plethysmograph method. The vascular function in vitro, the ROS levels by the DCFH-DA method and the expression of H2S-synthesizing enzymes and eNOS by Western blot were measured in isolated thoracic aortas at day 7 post-TBI. The effect of L-NAME on NaHS-induced effects in vascular function was evaluated. Brain water content was determined 7 days after trauma induction. Body weight was recorded throughout the experimental protocol, whereas the sensorimotor function was evaluated using the neuroscore test at days -1 (basal), 2, and 7 after the TBI induction. KEY FINDINGS: TBI animals showed: 1) an increase in hemodynamic variables and ROS levels in aortas; 2) vascular dysfunction; 3) sensorimotor dysfunction; and 4) a decrease in body weight, the expression of H2S-synthesizing enzymes, and eNOS phosphorylation. Interestingly, NaHS subchronic administration (3.1 mg/kg; i.p.; every 24 h for six days) prevented the development of hypertension, vascular dysfunction, and oxidative stress. L-NAME abolished NaHS-induced effects. Furthermore, NaHS treatment restored H2S-synthesizing enzymes and eNOS phosphorylation with no effect on body weight, sensorimotor impairments, or brain water content. SIGNIFICANCE: Taken together, these results demonstrate that H2S prevents TBI-induced hypertension by restoring vascular function and modulating ROS levels, H2S-synthesizing enzymes expression, and eNOS phosphorylation.


Subject(s)
Brain Injuries, Traumatic , Hydrogen Sulfide , Hypertension , Animals , Rats , Hydrogen Sulfide/pharmacology , Reactive Oxygen Species/metabolism , NG-Nitroarginine Methyl Ester/adverse effects , Hypertension/metabolism , Brain Injuries, Traumatic/complications , Brain Injuries, Traumatic/drug therapy , Body Weight , Water
6.
J Hazard Mater ; 444(Pt B): 130425, 2023 02 15.
Article in English | MEDLINE | ID: mdl-36435046

ABSTRACT

Inoculation with growth-promoting rhizobacteria inoculation and the addition of exogenous signaling molecules are two distinct strategies for improving heavy metal resistance and promoting growth in crops through several mechanisms. However, whether rhizobacteria and phyllosphere signaling molecules can act synergistically alleviate heavy metal stress and promote growth and the mechanisms underlying these effects remain unclear. Here, a novel strategy involving the co-application of growth-promoting rhizobacteria and an exogenous signaling molecule was developed to reduce cadmium (Cd) phytotoxicity and promote pak choi growth in Cd-contaminated soil. We found that the co-application of Azospirillum brasilense and hydrogen sulfide (H2S) resulted in significant improvements in shoot biomass and antioxidant enzyme content and a decline in the levels of Cd translocation factors. In addition, this co-application significantly improved pak choi Cd resistance. Furthermore, we observed a significant negative correlation between abscisic acid concentration and Cd content of pak choi and a positive correlation between H2S concentration and biomass. These findings revealed that the co-application of rhizobacteria and exogenous signaling molecules synergistically promoted the growth of vegetable crops subjected to heavy metal stress. Our results may serve as a guide for improving the food safety of crops grown in soil contaminated with heavy metals.


Subject(s)
Azospirillum brasilense , Brassica , Cadmium/toxicity , Abscisic Acid , Crops, Agricultural , Soil
7.
Environ Monit Assess ; 194(8): 563, 2022 Jul 05.
Article in English | MEDLINE | ID: mdl-35789438

ABSTRACT

A flare stack is an indispensable device in the oil and gas industry for allowing the safe combustion of gases into the atmosphere, especially during emergencies. However, it is not ideal for the routine disposal of gaseous waste, as it is subject to meteorological influences and poor operational control. In addition, it can be affected by toxic currents and thus pose a potential risk of odors; in view of this, an assessment must be made of the implications of burning on the environment and health. Atmospheric dispersion modelling has proved to be a very useful tool for this purpose. In light of this, an attempt has been made in this work to evaluate the impact of H2S on the well-being (odor perception) of the community in the surrounding area of an oil refinery, where the temporary burning of rich gas in H2S occurs in a chemical flare, and operational factors have an influence on atmospheric dispersion. The odor assessment was carried out with the aid of AERMOD which was adapted to estimate the maximum odor concentration for very short periods by means of peak-to-mean ratios. The results showed that H2S detection can reach a probability rate of 42% at 3.5 km distance from the flare (in a time interval of 5 s) with a relatively high degree of annoyance (3.0 AU). However, some operational procedures can reduce the probability of odor detection to 29% and the degree of annoyance to 2.6 AU.


Subject(s)
Environmental Monitoring , Odorants , Atmosphere , Gases , Oil and Gas Industry
8.
Cells ; 11(6)2022 03 09.
Article in English | MEDLINE | ID: mdl-35326383

ABSTRACT

The infection with SARS-CoV-2 impairs the glucose−insulin axis and this contributes to oxidative (OS) and nitrosative (NSS) stress. Here, we evaluated changes in glucose metabolism that could promote the loss of redox homeostasis in COVID-19 patients. This was comparative cohort and analytical study that compared COVID-19 patients and healthy subjects. The study population consisted of 61 COVID-19 patients with and without comorbidities and 25 healthy subjects (HS). In all subjects the plasma glucose, insulin, 8-isoprostane, Vitamin D, H2S and 3-nitrotyrosine were determined by ELISA. The nitrites (NO2−), lipid-peroxidation (LPO), total-antioxidant-capacity (TAC), thiols, glutathione (GSH) and selenium (Se) were determined by spectrophotometry. The glucose, insulin and HOMA-IR (p < 0.001), 8-isoprostanes, 3-nitrotyrosine (p < 0.001) and LPO were increased (p = 0.02) while Vitamin D (p = 0.01), H2S, thiols, TAC, GSH and Se (p < 0.001) decreased in COVID-19 patients in comparison to HS. The SARS-CoV-2 infection resulted in alterations in the glucose−insulin axis that led to hyperglycemia, hyperinsulinemia and IR in patients with and without comorbidities. These alterations increase OS and NSS reflected in increases or decreases in some oxidative markers in plasma with major impact or fatal consequences in patients that course with metabolic syndrome. Moreover, subjects without comorbidities could have long-term alterations in the redox homeostasis after infection.


Subject(s)
COVID-19 , Hyperglycemia , Insulin Resistance , Selenium , Antioxidants/metabolism , Glucose , Glutathione/metabolism , Homeostasis , Humans , Hyperglycemia/complications , Insulin/metabolism , Oxidation-Reduction , Oxidative Stress , SARS-CoV-2 , Sulfhydryl Compounds , Vitamin D , Vitamins
9.
Rev. biol. trop ; Rev. biol. trop;69(3)sept. 2021.
Article in English | LILACS, SaludCR | ID: biblio-1387677

ABSTRACT

Abstract Introduction: Coastal ecosystems worldwide are under the influence of local, regional and global stressors, such as pollution, eutrophication and climate change. Golfo Dulce is a relatively pristine and accessible deep tropical ecosystem that provides opportunities for comparative and collaborative research. Objective: To summarize published reports on past research conducted in this ecosystem, identify topics for further study, and suggest new research issues. Methods: A search was made on the web for reports based on research conducted in Golfo Dulce and published in scientific journals. Reports focusing on environmental parameters and on the biota were included. Results: A total of 123 studies that include data from Golfo Dulce are cited. The four topics more frequently addressed were reports based on the results of the R/V Victor Hensen expedition (1993-1994) and follow-up work on microbiology, studies on water parameters, research on vertebrates, and zooplankton studies. The reports focusing on vertical profiles of oxygen and temperature are discussed in detail, followed by those on the biota. Conclusions: Golfo Dulce has low oxygen concentrations below 50 m and is frequently anoxic at the 200 m deep basin with occasional formation of H2S. However, the ecosystem contains a relatively high diversity of identified organisms, from bacteria to whales. Of particular relevance for future studies are multidisciplinary surveys aiming at obtaining data on primary productivity, the diversity and biomass of the main groups of planktonic, demersal and benthic organisms, and the frequency and magnitude of the influx of deep offshore waters over the sill into the basin. These data, as well as the information gathered in the past, are essential for updating the trophic model developed more than 25 years ago and in support of new predictive models on the functioning of the ecosystem.


Resumen Introducción: Los ecosistemas costeros alrededor del mundo están bajo la influencia de tensores locales, regionales y globales, como la contaminación, la eutroficación y el cambio climático. El Golfo Dulce es un profundo ecosistema tropical relativamente inalterado y accesible, que provee oportunidades para la investigación comparativa y colaborativa. Objetivo: Resumir los informes publicados sobre investigaciones pasadas realizadas en el ecosistema, identificar tópicos para estudios futuros y sugerir nuevas áreas de investigación. Métodos: Se hizo una búsqueda en la red de informes basados en investigaciones hechas en Golfo Dulce y publicadas en revistas científicas. Fueron incluidos aquellos informes sobre parámetros ambientales y la biota. Resultados: Un total de 123 estudios que incluyen datos sobre Golfo Dulce son citados. Los cuatro tópicos citados con más frecuencia fueron: Los resultados de la expedición del R/V Victor Hensen (1993-1994) y estudios de seguimiento sobre microbiología, informes sobre parámetros acuáticos, investigaciones sobre vertebrados y estudios sobre zooplancton. Los informes sobre perfiles de oxígeno y temperatura son presentados con mayor detalle, seguidos por aquellos sobre la biota. Conclusiones: Golfo Dulce tiene bajas concentraciones de oxígeno por debajo de 50 m y es usualmente anóxico a 200 m en el fondo, con formación ocasional de H2S. Sin embargo, el ecosistema contiene una diversidad de organismos identificados relativamente alta, desde bacterias hasta ballenas. De relevancia particular para futuros estudios es, entre otros, la conducción, de muestreos multidisciplinarios orientados a obtener datos sobre productividad primaria, la diversidad y biomasa de los principales grupos de organismos planctónicos, demersales y bénticos, así como la frecuencia y magnitud del flujo de agua oceánica hacia el interior. Estos datos, así como los obtenidos en el pasado, son esenciales para actualizar el modelo trófico desarrollado hace más de 25 años, o en apoyo de nuevos modelos predictivos de funcionamiento del ecosistema.


Subject(s)
Tropical Ecosystem , Environmental Change , Climate Change , Costa Rica
10.
Electron. j. biotechnol ; Electron. j. biotechnol;50: 23-28, Mar. 2021. graf, ilus
Article in English | LILACS | ID: biblio-1292311

ABSTRACT

BACKGROUND: H2S is proved to be functioning as a signaling molecule in an array of physiological processes in the plant and animal kingdom. However, the H2S synthesis pathway and the responses to cold conditions remain unclear in postharvest mushroom. RESULTS: The biosynthesis of H2S in the Agaricus bisporus mushroom tissues exhibited an increasing tendency during postharvest storage and was significantly triggered by cold treatment. The cystathionine clyase (AbCSE) and cystathionine b-synthase (AbCBS) genes were cloned and proved responsible for H2S biosynthesis. Furthermore, transcriptional and posttranscriptional regulation of AbCSE and AbCBS were crucial for the enzyme activities and subsequent H2S levels. However, the AbMST was not involved in this process. Moreover, the AbCSE and AbCBS genes displayed low identity to the characterized genes, but typical catalytic domains, activity sites, subunit interface sites, and cofactor binding sites were conserved in the respective protein sequences, as revealed by molecular modeling and docking study. The potential transcription factors responsible for the H2S biosynthesis in cold conditions were also provided. CONCLUSIONS: The H2S biosynthetic pathway in postharvest mushroom was unique and distinct to that of other horticultural products.


Subject(s)
Agaricus/chemistry , Cystathionine beta-Synthase/metabolism , Cystathionine gamma-Lyase/metabolism , Hydrogen Sulfide/chemical synthesis , Crop Production , Agaricus campestris , Cold Temperature , Food Storage
11.
Waste Manag ; 120: 76-84, 2021 Feb 01.
Article in English | MEDLINE | ID: mdl-33285376

ABSTRACT

A two-stage bioreactor operated under anoxic denitrifying conditions was evaluated for desulfurization of synthetic biogas laden with H2S concentrations between 2500 and 10,000 ppmv. H2S removal efficiencies higher than 95% were achieved for H2S loads ranging from 16.2 to 51.9 gS mliquid-3h-1. Average H2S oxidation performance (fraction of S-SO42- produced per gram of S-H2S absorbed) ranged between 8.2 ± 1.2 and 18.7 ± 5.3% under continuous liquid operation. Nitrogen mass balance showed that only 2-6% of the N-NO3- consumed was directed to biomass growth and the rest was directed to denitrification. Significant changes in the bacterial community composition did not hinder the H2S removal efficiency. The bioreactor configuration proposed avoided clogging issues due to elemental sulfur accumulation as commonly occurs in packed bed bioreactors devoted to H2S-rich biogas desulfurization.


Subject(s)
Biofuels , Hydrogen Sulfide , Bioreactors , Denitrification , Nitrates , Sulfur
12.
New Phytol ; 230(2): 451-456, 2021 04.
Article in English | MEDLINE | ID: mdl-33251582

ABSTRACT

Hydrogen sulphide (H2 S) is an endogenously produced gasotransmitter that has rapidly emerged as an active signalling component of several plant processes, stomatal movement regulation among them. The guard cells (GCs), pairs of cells that neighbour the stomatal pores, transduce endogenous and environmental signals, through signalling network, to control stomatal pore size. In this complex network, which has become a model system for plant signalling, few highly connected components form a core that links most of the pathways. The evidence summarized in this insight, on the interplay between H2 S and different key components of the GC networks, points towards H2 S as a regulator of the GC core signalling pathway.


Subject(s)
Hydrogen Sulfide , Abscisic Acid , Plant Stomata , Signal Transduction
13.
Front Cell Neurosci ; 14: 17, 2020.
Article in English | MEDLINE | ID: mdl-32194376

ABSTRACT

Exposure to toxic metals and metalloids is an important cause of preventable diseases worldwide. Inorganic arsenic (iAs) affects several organs and tissues, causing neurobehavioral alterations in the central nervous system (CNS) that might lead to neurodegeneration. In this work, we wanted to explore the time- and dose-related changes on glutathione (GSH) levels in several regions of the CNS, such as the cortex, striatum, hippocampus, and cerebellum, to identify the initial cellular changes associated to GSH depletion due to iAs exposure. Mice received a single intraperitoneal injection containing 5 or 14 mg/kg sodium arsenite. Animals were killed at 2, 6, and 24 h. Significant depletion of GSH levels was observed in the cortex at 2 and 6 h, while on the striatum, hippocampus, or cerebellum regions, no significant changes were observed. GSH depletion in the cortex was associated with the activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) and nuclear factor kappa B (NFκB) pathways, which led to the upregulation of xCT, excitatory amino acid carrier 1 (EAAC1), glutamate/aspartate transporter (GLAST), and glial glutamate transporter 1 (GLT-1), and the activation of the transsulfuration pathways, which led to the overproduction of H2S in the cortex and increased levels of GSH in the cortex and cerebellum at 24 h. In the cortex, the N-methyl-D-aspartate (NMDA) receptor subunits NR2A and NR2B were also altered at 24 h. These early effects were not homogeneous among different brain regions and indicate early neurotoxic alterations in the cortex and cerebellum.

14.
Environ Sci Pollut Res Int ; 27(14): 15959-15966, 2020 May.
Article in English | MEDLINE | ID: mdl-30903467

ABSTRACT

A theoretical framework was developed and validated for the estimation of H2S concentration in biogas produced from complex sulfur-rich effluents. The modeling approach was based on easy-to-obtain data such as biological biogas potential (BBP), chemical oxygen demand, and total sulfur content. Considering the few data required, the model fitted well the experimental H2S concentrations obtained from BBP tests and continuous bioreactors reported in the literature. The model supported a correlation coefficient (R2) of 0.989 over the experimental data, obtaining average and maximum errors of ~ 25 and ~ 35%, respectively. The theoretical framework yielded good estimations for a wide range of experimental H2S concentrations (0.2 to 4.5% in biogas). This modeling approach is, therefore, a useful tool towards anticipating the H2S concentration in biogas produced from sulfur-rich substrates and deciding whether the installation of a desulfurization technology is required or not.


Subject(s)
Biofuels , Hydrogen Sulfide , Bioreactors , Sulfur
15.
Molecules ; 24(5)2019 Mar 11.
Article in English | MEDLINE | ID: mdl-30862086

ABSTRACT

Recently, our research group demonstrated that uvaol and ursolic acid increase NO and H2S production in aortic tissue. Molecular docking studies showed that both compounds bind with high affinity to endothelial NO synthase (eNOS) and cystathionine gamma-lyase (CSE). The aim of this study was to identify hits with high binding affinity for the triterpene binding-allosteric sites of eNOS and CSE and to evaluate their vasodilator effect. Additionally, the mechanism of action of the most potent compound was explored. A high-throughput virtual screening (HTVS) of 107,373 compounds, obtained from four ZINC database libraries, was performed employing the crystallographic structures of eNOS and CSE. Among the nine top-scoring ligands, isoxsuprine showed the most potent vasodilator effect. Pharmacological evaluation, employing the rat aorta model, indicated that the vasodilation produced by this compound involved activation of the NO/cGMP and H2S/KATP signaling pathways and blockade of α1-adrenoceptors and L-type voltage-dependent Ca2+ channels. Incubation of aorta homogenates in the presence of isoxsuprine caused 2-fold greater levels of H2S, which supported our preliminary in silico data. This study provides evidence to propose that the vasodilator effect of isoxsuprine involves various mechanisms, which highlights its potential to treat a wide variety of cardiovascular diseases.


Subject(s)
Adrenergic alpha-1 Receptor Antagonists/pharmacology , Calcium Channel Blockers/pharmacology , Isoxsuprine/chemistry , Isoxsuprine/pharmacology , Metabolic Networks and Pathways/drug effects , Quantitative Structure-Activity Relationship , Vasodilator Agents/chemistry , Vasodilator Agents/pharmacology , Adenosine Triphosphate/metabolism , Adrenergic alpha-1 Receptor Antagonists/chemistry , Calcium Channel Blockers/chemistry , Cyclic GMP/metabolism , Dose-Response Relationship, Drug , High-Throughput Screening Assays , Humans , Hydrogen Sulfide/metabolism , Molecular Docking Simulation , Molecular Dynamics Simulation , Nitric Oxide/metabolism , Small Molecule Libraries , Workflow
16.
Chemosphere ; 222: 732-741, 2019 May.
Article in English | MEDLINE | ID: mdl-30738316

ABSTRACT

The removal of toxic hydrogen sulfide (H2S) from the air at pilot-scale with elemental sulfur recovery was evaluated using Fe-EDTA chelate as a single treatment at a pH of about 8.5. This was later combined with a compost biofiltration process for polishing the pre-treated air. Experiments were performed in a unique container system that allowed deploying either Fe-EDTA chelate or Fe-EDTA chelate/biofiltration treatment (hybrid system). The results showed the feasibility of H2S removal at concentrations between 200 and 5300 ppmv (H2S loading rates of 7-190 g m-3 h-1) present in fouled air. The Fe-EDTA chelate as a single treatment was able to remove nearly 99.99% of the H2S at inlet concentrations ≤ 2400 ppmv (107 g m-3 h-1), while the hybrid system archived undetectable outlet H2S concentrations (<1 ppmv) at inlet levels of 4000 and 5300 ppmv. At 5300 ppmv, the Fe-EDTA chelate process H2S removal efficiency decreased to 99.20% due to the limitation of oxygen mass transfer in the Fe(III) regeneration reaction. Under the previous conditions, the pH was required to be controlled by the addition of NaOH, due to the likely occurrence of undesirable parallel reactions. The elemental sulfur yield attained in the physicochemical module was 75-93% with around 80% recovered efficiently as a solid.


Subject(s)
Environmental Restoration and Remediation/methods , Ferric Compounds/pharmacology , Hydrogen Sulfide/isolation & purification , Sulfur/isolation & purification , Air Pollutants/isolation & purification , Edetic Acid/pharmacology , Iron Chelating Agents/pharmacology , Oxygen , Pilot Projects
17.
Biotechnol Rep (Amst) ; 20: e00293, 2018 Dec.
Article in English | MEDLINE | ID: mdl-30568887

ABSTRACT

Microaeration can be used to cost-effectively remove in-situ H2S from the biogas generated in anaerobic digesters. This study is aimed at developing and validating an extension of the Anaerobic Digestion Model n°1 capable of incorporating the main phenomena which occurs during microaeration. This innovative model was implemented and tested with data from a pilot scale digester microaerated for ∼ 200 d. The results showed that despite the model's initial ability to predict the digester's behavior, its predicted performance was improved by calibrating the most influential parameters. The model's prediction potential was largely enhanced by adding retention parameters that account for the activity of sulfide oxidizing bacteria retained inside the anaerobic digester, which have been consistently shown to be responsible for a large share of the H2S removed.

18.
Chemosphere ; 191: 809-816, 2018 Jan.
Article in English | MEDLINE | ID: mdl-29145133

ABSTRACT

Foul odors comprise generally a complex mixture of molecules, where reduced sulfur compounds play a key role due to their toxicity and low odor threshold. Previous reports on treating mixtures of sulfur compounds in single biofilters showed that hydrogen sulfide (H2S) interferes with the removal and degradation of other sulfur compounds. In this study, hydrogen sulfide (H2S) and dimethyl disulfide (DMDS) were fed to an alkaline biotrickling filter (ABTF) at pH 10, to evaluate the simultaneous removal of inorganic and organic sulfur compounds in a single, basic-pH system. The H2S-DMDS mixture was treated for more than 200 days, with a gas residence time of 40 s, attaining elimination capacities of 86 gDMDS m-3 h-1 and 17 gH2S m-3 h-1 and removal efficiencies close to 100%. Conversion of H2S and DMDS to sulfate was generally above 70%. Consumption of sulfide and formaldehyde was verified by respirometry, suggesting the coexistence of both methylotrophic and chemoautotrophic breakdown pathways by the immobilized alkaliphilic biomass. The molecular biology analysis showed that the long-term acclimation of the ABTF led to a great variety of bacteria, predominated by Thioalkalivibrio species, while fungal community was notoriously less diverse and dominated by Fusarium species.


Subject(s)
Disulfides/chemistry , Hydrogen Sulfide/chemistry , Waste Disposal, Fluid/methods , Bacteria/metabolism , Bioreactors , Disulfides/analysis , Filtration , Hydrogen Sulfide/analysis , Sulfates/metabolism , Sulfides/metabolism , Sulfur Compounds/metabolism
19.
Inflammopharmacology ; 26(1): 183-195, 2018 Feb.
Article in English | MEDLINE | ID: mdl-28707182

ABSTRACT

We evaluate the anti-inflammatory and antialgic potency of a nanoemulsion (NEORO) containing the essential oil of Rosmarinus officinalis L. (EORO), which is composed primarily of limonene, camphor and 1,8-cineole. The EORO and NEORO were administered orally 30 min prior to starting the experiments. In a test of rat paw oedema induced by carrageenan, NEORO was effective in doses of 498 µg/kg, and it inhibited 46% of the maximum peak of the oedema; in a dose of 300 mg/kg, EORO inhibited 50% of the maximum peak of the oedema. In an acetic acid-induced writhing test, NEORO yielded a dose-dependent effect, and a dose of 830 µg/kg inhibited 84% of the algesic process; a dose of 100 mg/kg of EORO inhibited 55%. In an assay for H2S production in rat stomachs, a dose of 498 µg/kg of NEORO inhibited H2S production in all of the measurement phases, and a dose of 100 mg/kg EORO inhibited 60% and influenced the effect of the ethanol significantly, reducing the production of H2S. We suggest that NEORO potentiated the effect of EORO, demonstrating effectiveness in doses 600 times lower than those applied with EORO. Among the major compounds of EORO, the camphor molecule exhibited the largest number of interactions with the therapeutic targets related to the inflammatory process, suggesting that it is responsible for EORO's anti-inflammatory and antialgic effects. This work paves the way for future investigations related to the therapeutic role of NEORO in the inflammation process.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Emulsions/pharmacology , Inflammation/drug therapy , Nanoparticles/administration & dosage , Oils, Volatile/pharmacology , Plant Extracts/pharmacology , Rosmarinus/chemistry , Animals , Carrageenan/pharmacology , Cyclohexenes/pharmacology , Edema/chemically induced , Edema/drug therapy , Limonene , Male , Molecular Docking Simulation/methods , Rats , Rats, Wistar , Terpenes/pharmacology
20.
Braz. J. Pharm. Sci. (Online) ; 54(3): e17259, 2018. tab, graf
Article in English | LILACS | ID: biblio-974419

ABSTRACT

Coconut milk (CCM) has been an important cooking ingredient in the Asia-Pacific region since ancient time. Due to its high content of saturated fatty acids, it has been considered atherogenic. We have tested if chronic consumption of fresh coconut milk by middle-aged male rat affects vascular function, plasma glucose and lipid profiles. Compared to control, CCM caused lower maximal contraction to phenylephrine of thoracic aortic rings and increased relaxation to acetylcholine that was abolished by N G-nitro-L-arginine (L-NA) or disruption of the endothelium. DL-propargylglycine caused slight increase in baseline tension of L-NA treated aortic rings of CCM-treated rats and produced higher contractile response of the aortic rings to low concentrations of phenylephrine. The aortic eNOS- and cystathionine-γ-lyase(CSE) proteins expression of the CCM-treated rats were also higher than in controls. Except for lower fasting plasma glucose there were no changes in blood chemistry for the CCM treated rats. CCM consumption caused up-regulation of eNOS and CSE protein expression which resulted in increased production of NO and H2S from the blood vessels with attenuation of vasocontraction to phenylephrine and increased relaxation to acetylcholine. These novel benefits may be expected to reduce the development of cardiovascular risk factors in the aging rat


Subject(s)
Animals , Male , Rats , Eating , Foods Containing Coconut , Palm Oil/analysis , Aorta, Thoracic , Cardiovascular System
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