Effect of therapeutic plasma concentrations of non-steroidal anti-inflammatory drugs on the production of reactive oxygen species by activated rat neutrophils

Paino, Iêda Maria Martinez; Ximenes, Valdecir Farias; Fonseca, Luiz Marcos da; Kanegae, Marilia P. P.; Khalil, Najeh Maissar; Brunetti, Iguatemy Lourenço

doi:10.1590/s0100-879x2005000400007

Cited by 36 publications

(23 citation statements)

References 33 publications

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“…The assay for HOCl generation by MPO in vitro was adapted from the procedure described by Paino et al (13). Aliquots of 100 l of each serum diluted 1:10 were deposited into wells of the microtitration plates (Black Optiplate; Packard, Warrenville, IL) coated with MPO as described above and incubated for 60 minutes at room temperature.…”

Section: Methodsmentioning

confidence: 99%

Pathogenic effects of antimyeloperoxidase antibodies in patients with microscopic polyangiitis

Guilpain¹,

Servettaz²,

Goulvestre³

et al. 2007

Arthritis & Rheumatism

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Objective. Microscopic polyangiitis (MPA) is a small-vessel vasculitis associated with antimyeloperoxidase (MPO) antibodies in 70% of patients. Anti-MPO antibodies can trigger the release of MPO by neutrophils and monocytes, but their involvement in the pathogenesis of MPA is still questioned. The aim of this study was to investigate whether anti-MPO antibodies can activate MPO to generate an oxidative stress that is potentially deleterious to the endothelium.Methods. MPA sera, purified IgG from MPA sera, normal control sera, and purified IgG from normal sera were incubated with MPO coated onto microtitration plates. The peroxidase activity of MPO was evaluated by adding o-phenylenediamine. Production of hypochlorous acid (HOCl) was determined by chemiluminescence. The cytotoxic properties of byproducts of MPO activation were tested on endothelial cells in culture.Results. MPA sera with anti-MPO antibodies were found to activate MPO in vitro (P < 0.0001 versus normal sera) and to generate HOCl (P < 0.001), as did IgG purified from MPA sera (P < 0.05). MPA sera without anti-MPO antibodies and MPA IgG absorbed on MPO did not show these activities. The byproducts of MPO activation by MPA sera exerted a strong cytolytic activity on endothelial cells in culture (P < 0.01). Both HOCl production and endothelial lysis were abrogated by N-acetylcysteine (NAC), an antioxidant molecule (P < 0.05 and P < 0.0001, respectively).Conclusion. Anti-MPO antibodies could play a pathogenic role in vivo by triggering an oxidative burst, leading to severe endothelial damage. Treatment of MPA patients with NAC might be proposed in an attempt to abrogate these deleterious phenomena.Microscopic polyangiitis (MPA) is a small-vessel vasculitis with frequent cutaneous, pulmonary, renal, and neurologic involvement. Antineutrophil cytoplasmic autoantibodies (ANCAs) are detectable in the sera of ϳ70% of MPA patients and are mainly directed toward myeloperoxidase (MPO) (1,2). MPO is a 118-kd cationic protein that is present in primary azurophilic granules of polymorphonuclear neutrophils (PMNs) and monocytes. MPO uses hydrogen peroxide and chloride ions to generate hypochlorous acid (HOCl), a highly deleterious reactive oxygen species (ROS) that contributes to oxidative burst from PMNs in response to microbial infections (3).The pathogenic role of anti-MPO IgG antibodies has recently been suggested by studies of the passive transfer of anti-MPO antibodies into Rag2 -/-mice, which was followed by the development of necrotizing crescentic glomerulonephritis and systemic vasculitis mimicking the disease in humans (4). However, the mechanism of the pathogenicity of anti-MPO antibodies is not completely understood. Some reports have suggested that anti-MPO antibodies can activate PMNs and monocytes and lead to the extracellular release of MPO and oxidative burst (5,6). We have hypothesized that, as already shown for proteinase 3 (PR3) (7,8), serum

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Section: Methodsmentioning

confidence: 99%

Pathogenic effects of antimyeloperoxidase antibodies in patients with microscopic polyangiitis

Guilpain¹,

Servettaz²,

Goulvestre³

et al. 2007

Arthritis & Rheumatism

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“…Neutrophils (PMN) were isolated according to Paino et al (2005). PMN were obtained from 6 male adults (100-160 grams) Rattus norvegicus var.…”

Section: Mpo Extraction From Pmnmentioning

confidence: 99%

Salacia campestris root bark extract: peroxidase inhibition, antioxidant and antiradical profile

Vellosa

Khalil

Gutierres

et al. 2009

Braz. J. Pharm. Sci.

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Reactive oxygen species (ROS) and free radical species have been implicated in initiating or accompanying many diseases in living organisms; there is thus, a continual need for antioxidants molecules to inactivate ROS/free radicals. Many studies of plants crude extracts have demonstrated free-radical scavenging and antioxidant action. Salacia species have long been used, in several countries, as traditional medicines against certain diseases and for their anti-inflammatory properties. In this study, Salacia campestris Walp (Hippocrateaceae) root bark ethanol extract (ScEtOH) was assessed for its ability to scavenge free radicals and reactive oxygen species; the results were expressed as percentage inhibition of the active species. ScEtOH was efficient against studied species: DPPH radical (obtained inhibition = 30%), ABTS•+ (IC 50 = 1.8±0.8 µg/mL), HOCl (IC 50 = 1.7 ± 0.1 µg/mL), O 2•-(obtained inhibition = 32%), and NO • (obtained inhibition = 18 %). Peroxidase activity inhibition was evaluated through the guaiacol oxidation reaction catalyzed by hemin, HRP and myeloperoxidase (MPO); data showed that ScEtOH at 10 µg/mL led to 54 and 51% of inhibition, respectively, for the hemin and HRP systems. In the MPO system, ScEtOH promoted a 50% inhibition at 8.9 µg/mL, whereas quercetin, a powerful MPO inhibitor, inhibited this system at 1.35 µg/mL. Espécies reativas do oxigênio (ERO) e radicais livres estão relacionados ao início ou à exacerbação de muitas doenças em organismos vivos; existindo portanto uma necessidade contínua por moléculas antioxidantes que inativem as ERO e radicais livres. Muitos estudos com extratos brutos de plantas têm demonstrado propriedades antioxidantes e seqüestradoras de radicais livres. Espécies de Salacia são utilizadas, em muitos países, como remédio tradicional contra certas doenças e por suas propriedades antiinflamatórias. Neste estudo, o extrato bruto etanólico da casca da raiz da Salacia campestris Walp (Hippocrateaceae) foi avaliado quanto à sua habilidade em seqüestrar radicais livres e espécies reativas do oxigênio; os resultados são expressos como porcentagem de inibição das espécies ativas. ScEtOH mostrou-se eficiente frente as espécies estudadas: radical DPPH (inibição obtida = 30%), ABTS Uniterms•+ (IC 50 = 1,8±0,8 µg/mL), HOCl (IC 50 = 1,7 ± 0,1 µg/mL), O 2•-(inibição obtida = 32%), and NO • (inibição obtida = 18%). A inibição da atividade peroxidásica foi avaliada através da oxidação do guaiacol catalisada pela hemina, HRP e mieloperoxidase (MPO); os dados mostram que 10 µg/mL de ScEtOH promovem 54 e 51% de inibição, respectivamente para os sistemas da hemina e da HRP. No sistema da MPO, ScEtOH promoveu 50% de inibição na dose de 8,9 µg/mL, enquanto a quercetina, um potente inibidor da MPO promoveu tal inibição com 1,35 µg/mL. Unitermos: Salacia campestris Walp/propriedades antioxidantes Hippocrateaceae. Mieloperoxidase. Oxigênio/espécies reativas. Antioxidantes. Radicais livres.

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“…Diets rich in fruits and vegetables have been associated with lower cancer rates leading to various theories that their antioxidant content has protective effect against cancer development. Clinically, nonsteroidal anti-inflammatory drugs have been demonstrated to inhibit the generation of hypochlorous acid (a ROS) thereby, suppress the oxidative functions of neutrophils (Paino et al, 2005).…”

Section: Endogenous and Exogenous Management Of Ros Related Health Comentioning

confidence: 99%

“…Clinical use of non-steroid anti-inflammatory drugs has been shown to inhibit hypochlorous acid generation hence suppress oxidative functions of neutrophils (Paino et al, 2005). Clinically, ozone therapy has been successfully applied in the treatment of spinal disk herniation as compared to surgical procedures (Bocci, 2005;Bocci et al, 2015).…”

Section: Endogenous and Exogenous Management Of Ros Related Health Comentioning

confidence: 99%

Reactive oxygen species (ROS) generation, impacts on tissue oxidation and dietary management of non-communicable diseases: A review

Wafula¹,

Arnold²,

Calvin³

et al. 2017

Afr. J. Biochem. Res.

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Generation of reactive oxygen species (ROS) in biological systems has been reported to be a significant cause of inflammatory and metabolic diseases. More recently, ROS and in a particular ozone has also been implicated in the conversion of cholesterol to atherogenic compounds, secosterol A, and upon aldolization to secosterol-B. Secosterol-A is uniquely produced by cholesterol ozonolysis, while secosterol-B can also be generated through the reaction of cholesterol with singlet oxygen. On the other hand, lipid oxidation reactions generate hydroperoxides, which upon catalytic and/or enzymatic decomposition yields lipid peroxide products of significant importance to tissue health. The mechanism of formation of potent oxidants like ozone in biological systems has not been clearly demonstrated, with only a theory: That antibodies catalyze oxidation of water by singlet oxygen to yield a trioxidic species, like hydrogen trioxide, as an intermediate in hydrogen peroxide formation while a recent hypothesis indicates that ozone could also be an intermediate in the aforementioned pathway and could be generated from biological molecules in the presence of singlet oxygen. Similarly, there is new information being generated concerning the involvement of antioxidants and amino acids in either termination or propagation of oxidative processes in mammalian systems. This review explores mechanisms of ROS/ozone generation in tissues, lipid peroxidation, cholesterol oxidation and highlight dietary management of non-communicable diseases with a focus on the roles of antioxidants and amino acids.

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Effect of therapeutic plasma concentrations of non-steroidal anti-inflammatory drugs on the production of reactive oxygen species by activated rat neutrophils

Cited by 36 publications

References 33 publications

Pathogenic effects of antimyeloperoxidase antibodies in patients with microscopic polyangiitis

Pathogenic effects of antimyeloperoxidase antibodies in patients with microscopic polyangiitis

Salacia campestris root bark extract: peroxidase inhibition, antioxidant and antiradical profile

Reactive oxygen species (ROS) generation, impacts on tissue oxidation and dietary management of non-communicable diseases: A review

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