Ebselen Attenuates Lung Injury in Experimental Model of Carrageenan-Induced Pleurisy in Rats

Petronilho, Fabrícia; Florentino, Drielly; Silvestre, Fernanda; Danielski, Lucinéia Gainski; Nascimento, Diego Zapelini do; Vieira, Andriele; Κanis, Luiz Alberto; Fortunato, Jucélia Jeremias; Badawy, Marwa; Barichello, Tatiana; Quevedo, Joao L De

doi:10.1007/s10753-015-0113-5

Cited by 14 publications

(7 citation statements)

References 27 publications

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“…A number of studies have demonstrated the inhibitory actions of orally administered ebselen on lung inflammation in vivo. Experimental models in animals include pulmonary inflammation induced by carrageenin, sephadex, ozone, cigarette smoke and endotoxin [54][55][56][57]. In LPS-induced lung inflammation, ebselen inhibited leukocyte infiltration in association with lowered expression of ICAM-1 adhesion molecule and the inflammatory cytokines, TNFα and IL1β, in lung tissue [55].…”

Section: Ebselen and Lung Inflammationmentioning

confidence: 99%

Potential therapeutic use of ebselen for COVID-19 and other respiratory viral infections

Sies

Parnham

2020

Free Radical Biology and Medicine

151

146

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Ebselen is an organoselenium compound exhibiting hydroperoxide-and peroxynitrite-reducing activity, acting as a glutathione peroxidase and peroxiredoxin enzyme mimetic. Ebselen reacts with a multitude of protein thiols, forming a selenosulfide bond, which results in pleiotropic effects of antiviral, antibacterial and anti-inflammatory nature. The main protease (M pro ) of the corona virus SARS-CoV-2 is a potential drug target, and a screen with over 10,000 compounds identified ebselen as a particularly promising inhibitor of M pro (Jin, Z. et al.(2020) Nature 582, 289-293). We discuss here the reaction of ebselen with cysteine proteases, the role of ebselen in infections with viruses and with other microorganisms. We also discuss effects of ebselen in lung inflammation. In further research on the inhibition of M pro in SARS-CoV-2, ebselen can serve as a promising lead compound, if the inhibitory effect is confirmed in intact cells in vivo. Independently of this action, potential beneficial effects of ebselen in COVID-19 are ascribed to a number of targets critical to pathogenesis, such as attenuation of inflammatory oxidants and cytokines.

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Section: Ebselen and Lung Inflammationmentioning

confidence: 99%

Potential therapeutic use of ebselen for COVID-19 and other respiratory viral infections

Sies

Parnham

2020

Free Radical Biology and Medicine

151

146

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“…Selenium, a GPx cofactor, activates GPx in vivo and attenuates lipid peroxidation and lung injury early after paraquat intoxication in rats, but did not affect the survival [152]. Ebselen, an organoselenium compound, mimics GPx activity and showed protective action in animal model of pleurisy [153]. BXT-51072 and BXT-51077, seleniumcontaining GPx mimics, prevented TNF-and neutrophil-induced endothelial alterations through the downregulation of endothelial proinflammatory responses [154].…”

Section: Glutathione and Related Enzymesmentioning

confidence: 99%

ROS Signaling in the Pathogenesis of Acute Lung Injury (ALI) and Acute Respiratory Distress Syndrome (ARDS)

Kellner

Noonepalle

Lü

et al. 2017

Advances in Experimental Medicine and Biology

286

256

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The generation of reactive oxygen species (ROS) plays an important role for the maintenance of cellular processes and functions in the body. However, the excessive generation of oxygen radicals under pathological conditions such as acute lung injury (ALI) and its most severe form acute respiratory distress syndrome (ARDS) leads to increased endothelial permeability. Within this hallmark of ALI and ARDS, vascular microvessels lose their junctional integrity and show increased myosin contractions that promote the migration of polymorphonuclear leukocytes (PMNs) and the transition of solutes and fluids in the alveolar lumen. These processes all have a redox component, and this chapter focuses on the role played by ROS during the development of ALI/ARDS. We discuss the origins of ROS within the cell, cellular defense mechanisms against oxidative damage, the role of ROS in the development of endothelial permeability, and potential therapies targeted at oxidative stress.

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“…The increase in the vascular permeability is characterized by exudation and it is considered as a major feature of acute inflammation in the inflammatory sites . There is evidence that MPO activity is an indirect marker of active neutrophils (representing 65% of leukocytes) and results in the exudation and migration of monomorphonuclear cells .…”

Section: Discussionmentioning

confidence: 99%

Further analysis of acute antinociceptive and anti‐inflammatory actions of 4‐phenylselenyl‐7‐chloroquinoline in mice

Silva

Reis

Pinz

et al. 2017

Fundamemntal Clinical Pharma

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A new quinoline containing selenium, 4-phenylselenyl-7-chloroquinoline (4-PSQ), was described and synthetized by our research group. Recently, we demonstrated the potential antinociceptive and anti-inflammatory of 4-PSQ. For this reason, the first objective of this study was to expand our previous findings by investigating the contribution of glutamatergic, serotonergic, and nitrergic systems to the acute antinociceptive action of this compound. Pretreatment with 4-PSQ (0.01-25 mg/kg, p.o.) reduced the nociception induced by glutamate. MK-801 (an uncompetitive antagonist of the N-Methyl-d-aspartate (NMDA) receptor) blocked the antinociceptive effect exerted by 4-PSQ (25 mg/kg, p.o.) in the acetic acid-induced abdominal writhing test. The pretreatment with WAY100635 (a selective antagonist of 5-HT receptor), ketanserin (a selective antagonist of 5-HT receptor), and pindolol (a nonselective antagonist of 5-HT receptors) partially blocked the antinociceptive effect caused by 4-PSQ (25 mg/kg, per oral, p.o.) in the acetic acid-induced abdominal writhing test. Nitric oxide precursor, l-arginine hydrochloride, partially reversed antinociception caused by 4-PSQ or ω-nitro-l-arginine (l-NOARG). Treatments did not modify the locomotor and exploratory activities of mice. Additionally, the acute anti-inflammatory effect of 4-PSQ in a model of pleurisy induced by carrageenan in mice was investigated. 4-PSQ reduced the cellular migration, pleural exudate accumulation, and myeloperoxidase activity induced by carrageenan exposure. 4-PSQ protected against the increase in reactive species levels and reduction of nonprotein thiol levels induced by carrageenan. Data presented here showed that the modulation of serotonergic, nitrergic, and glutamatergic systems contributed to the antinociceptive effect of 4-PSQ and it reinforced the therapeutic potential of this quinolinic compound for acute inflammation.

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Ebselen Attenuates Lung Injury in Experimental Model of Carrageenan-Induced Pleurisy in Rats

Cited by 14 publications

References 27 publications

Potential therapeutic use of ebselen for COVID-19 and other respiratory viral infections

Potential therapeutic use of ebselen for COVID-19 and other respiratory viral infections

ROS Signaling in the Pathogenesis of Acute Lung Injury (ALI) and Acute Respiratory Distress Syndrome (ARDS)

Further analysis of acute antinociceptive and anti‐inflammatory actions of 4‐phenylselenyl‐7‐chloroquinoline in mice

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