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      Bevacizumab Diminishes Inflammation in an Acute Endotoxin-Induced Uveitis Model

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          Abstract

          Introduction: Uveitis is an eye disease characterized by inflammation of the uvea and an early and exhaustive diagnosis is essential for its treatment. The aim of our study is to assess the potential toxicity and anti-inflammatory efficacy of Bevacizumab in an experimental uveitis model by subcutaneously injecting lipopolysaccharide into Lewis rats and to clarify its mechanism.

          Material and Methods: Blood–aqueous barrier integrity was assessed 24 h after endotoxin-induced uveitis (EIU) by analyzing two parameters: cell count and protein concentration in aqueous humors. Histopathology of all eye structures was also studied. Enzyme-linked immunosorbent analyses of the aqueous humor samples were performed in order to calculate the diverse chemokine and cytokine protein levels and oxidative stress-related markers were also evaluated.

          Results: The aqueous humor’s cellular content significantly increased in the group treated with only Bevacizumab, but it had no effect on retina histopathological grading. Nevertheless, the inflammation noted in ocular structures when administering Bevacizumab with endotoxin was mostly prevented since aqueous humor cell content considerably lowered, and concomitantly with a sharp drop in uveal, vitreous, and retina histopathological grading. The values of the multi-faceted cytokine IL-2 also significantly decreased ( p < 0.05 vs. endotoxin group), and the protective IL-6 and IL-10 cytokines values rose with related anti-oxidant system recovery ( p < 0.05 vs. endotoxin group). Concurrently, some related M1 macrophage chemokines substantially increased, e.g., GRO/KC, a chemokine that also displays any kind of protective role.

          Conclusion: All these results revealed that 24 h after being administered, Bevacizumab treatment in EIU significantly prevented inflammation in various eye structures and correct results in efficacy vs. toxicity balance were obtained.

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          Most cited references72

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          A simplification of the protein assay method of Lowry et al. which is more generally applicable.

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            Adverse events and complications associated with intravitreal injection of anti-VEGF agents: a review of literature.

            Intravitreal injection of anti-vascular endothelial growth factor (VEGF) agents is increasingly used for the treatment of a wide variety of retinal diseases, including age-related macular degeneration, diabetic retinopathy and retinal vascular occlusions, and retinopathy of prematurity. Despite encouraging results in halting the disease and improving the vision, intravitreal injection of anti-VEGF agents may be associated with systemic adverse events and devastating ocular complications. In this review, we provide an overview of safety data for intravitreal injection of common anti-VEGF agents.
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              From IL-2 to IL-37: the expanding spectrum of anti-inflammatory cytokines.

              Feedback regulatory circuits provided by regulatory T cells (T(reg) cells) and suppressive cytokines are an intrinsic part of the immune system, along with effector functions. Here we discuss some of the regulatory cytokines that have evolved to permit tolerance to components of self as well as the eradication of pathogens with minimal collateral damage to the host. Interleukin 2 (IL-2), IL-10 and transforming growth factor-β (TGF-β) are well characterized, whereas IL-27, IL-35 and IL-37 represent newcomers to the spectrum of anti-inflammatory cytokines. We also emphasize how information accumulated through in vitro as well as in vivo studies of genetically engineered mice can help in the understanding and treatment of human diseases.
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                Author and article information

                Contributors
                Journal
                Front Pharmacol
                Front Pharmacol
                Front. Pharmacol.
                Frontiers in Pharmacology
                Frontiers Media S.A.
                1663-9812
                19 June 2018
                2018
                : 9
                : 649
                Affiliations
                [1] 1Departamento de Ciencias Biomédicas, Instituto de Ciencias Biomédicas, Universidad Cardenal Herrera-CEU, CEU Universities , Valencia, Spain
                [2] 2Department of Pathology, University of Valencia , Valencia, Spain
                [3] 3Department of Medical Ophtalmology, Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana , Valencia, Spain
                [4] 4Department of Basic Sciences, Universidad Católica de Valencia San Vicente Mártir , Valencia, Spain
                Author notes

                Edited by: Patrizia Ballerini, Università degli Studi G. d’Annunzio Chieti–Pescara, Italy

                Reviewed by: Simone Guarnieri, Università degli Studi G. d’Annunzio Chieti–Pescara, Italy; Mirko Pesce, Università degli Studi G. d’Annunzio Chieti–Pescara, Italy; Andrew Dellinger, Elon University, United States

                *Correspondence: Francisco Bosch-Morell, fbosch@ 123456uch.ceu.es

                This article was submitted to Inflammation Pharmacology, a section of the journal Frontiers in Pharmacology

                Article
                10.3389/fphar.2018.00649
                6018210
                5e5d64fa-e486-44c9-afc7-fa04aae07e00
                Copyright © 2018 Mérida, Sancho-Tello, Almansa, Desco, Peris, Moreno, Villar, Navea and Bosch-Morell.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 26 November 2017
                : 31 May 2018
                Page count
                Figures: 5, Tables: 1, Equations: 0, References: 82, Pages: 11, Words: 0
                Categories
                Pharmacology
                Original Research

                Pharmacology & Pharmaceutical medicine
                bevacizumab,endotoxin-induced uveitis,inflammation,oxidative stress,chemokines,cytokines

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