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      Firocoxib on aqueous humor prostaglandin E 2 levels for controlling experimentally-induced breakdown of blood-aqueous barrier in healthy and Toxoplasma gondii -seropositive cats Translated title: Efeitos do firocoxib sobre os níveis de prostaglandina E 2 no humor aquoso de gatos saudáveis e com sorologia positiva para toxoplasmose mediante quebra da barreira hematoaquosa experimentalmente induzida

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          Abstract

          ABSTRACT: This study aimed to evaluate the effects of firocoxib for controlling experimentally-induced breakdown of the blood-aqueous barrier in healthy and Toxoplasma gondii -seropositive cats. Thirty two cats with no ocular abnormalities were used. Groups (n=8/each) were formed with healthy cats that received 5mg g-1 of oral firocoxib (FH) or no treatment (CH) on day 0; seropositive cats for anti -T. gondii specific immunoglobulin G (IgG) were grouped (n=8/each) and treated in a similar fashion (FT and CT). On day 1, cats of all groups received the same treatment protocol, and 1h later, aqueocentesis was performed under general anesthesia (M0). Following 1h, the same procedure was repeated (M1). Quantitation of aqueous humor total protein and prostaglandin E2 (PGE2) were determined. Aqueous samples of seropositive cats were tested for anti- T. gondii specific IgG. In M0, aqueous samples of CT showed a significantly higher concentration of PGE2 in comparison with other groups (P<0.05). In all groups, PGE2 concentration increased significantly from M0 to M1 (P=0.001). PGE2 values did not change significantly between groups in M1 (P=0.17). Anti- T. gondii specific IgG were reported only in samples of M1, and aqueous titers did not change significantly between FT and CT (P=0.11). Although we have observed that aqueous humor PGE2 levels were significantly higher in cats of CT group during M0, such increase was not able to break the blood-aqueous barrier and cause anterior uveitis. Firocoxib did not prevent intraocular inflammation after aqueocentesis, in healthy and toxoplasmosis-seropositive cats.

          Translated abstract

          RESUMO: Objetivou-se avaliar a eficácia do firocoxib no controle da quebra da barreira hematoaquosa experimentalmente induzida em gatos saudáveis e com sorologia positiva para toxoplasmose. Para tanto, utilizaram-se trinta e dois gatos sem alterações oculares, alocados em grupos (n=8/cada) compostos por gatos saudáveis que receberam tratamento prévio com 5mg g-1 de firocoxib oral (HF) ou sem nenhum tratamento (CH) no dia 0, e por gatos com sorologia positiva para toxoplasmose tratados de maneira similar (FT e CT). No dia 1, os gatos de todos os grupos receberam o mesmo protocolo de tratamento do dia anterior e, 1h depois, foram submetidos à paracentese da câmara anterior sob anestesia geral (M0). Após 1h, realizou-se nova paracentese (M1). Mediante a colheita de humor aquoso (M0 e M1), quantificaram-se os valores de proteína total e prostaglandina E2 (PGE2) das amostras. As amostras dos gatos com sorologia positiva para toxoplasmose foram também testadas para anticorpos anti- T. gondii IgG específicos. Em M0, as amostras de humor aquoso de CT apresentaram concentração de PGE2 significativamente superior aos demais grupos (P<0,05). Em todos os grupos, a concentração de PGE2 aumentou significativamente de M0 para M1 (P=0,001), no entanto, não houve diferença significativa entre os grupos em M1 (P=0,17). Anticorpos anti -T. gondii IgG específicos foram encontrados somente em amostras de M1, e os títulos não diferiram significativamente entre FT e CT (P=0,11). Valores de PGE2 significativamente superiores no CT durante M0 não foram capazes de induzir a quebra da barreira hematoaquosa e causar uveíte anterior nos gatos deste estudo. O firocoxib, por sua vez, não foi capaz de prevenir a quebra da barreira hematoaquosa após realização de paracente na câmara anterior em gatos saudáveis e com sorologia positiva para toxoplasmose.

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          Most cited references39

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          IMPROVED TECHNIQUE OF INDIRECT IMMUNOFLUORESCENCE FOR SEROLOGICAL DIAGNOSIS OF TOXOPLASMOSIS.

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            Systematic review of nonsteroidal anti-inflammatory drug-induced adverse effects in dogs.

            The aim of this systematic review was to identify, assess, and critically evaluate the quality of evidence of nonsteroidal anti-inflammatory drug (NSAID)-induced adverse effects in dogs. Original prospective studies published in peer-reviewed journals in English (1990-2012) that reported data on the safety of NSAIDs administration in dogs were searched. For each study, design type (I, II, III, or IV) and assessment of quality (+, Ø, -) were rated. For each drug, quantity and consistency rating (***, **, *) and strength of evidence (high, moderate, low, or extremely low) were identified and evaluated. The strength of evidence was defined in terms of how applicable and relevant the conclusions were to the target population. Sixty-four studies met the inclusion criteria. Thirty-five (55%) research studies and 29 (45%) clinical trials were identified. A high strength of evidence existed for carprofen, firocoxib, and meloxicam; moderate for deracoxib, ketoprofen, and robenacoxib; and low for etodolac. Quality and consistency rating were as follows: carprofen (***/***), deracoxib (**/***), etodolac (*/unable to rate), firocoxib (***/**), ketoprofen (**/***), meloxicam (***/***), and robenacoxib (**/**), respectively. Adverse effects were detected in 35 studies (55%) and commonly included vomiting, diarrhea, and anorexia. Three studies (5%) reported a power analysis related to adverse effects of ≥80%. In randomized, placebo-controlled, blinded studies (n = 25, 39%), the incidence of adverse effects was not statistically different between treated and control dogs. Finally, most studies were not appropriately designed to determine the safety of NSAIDs, and involved a healthy nongeriatric population of research dogs.
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              Toxoplasma gondii-skeletal muscle cells interaction increases lipid droplet biogenesis and positively modulates the production of IL-12, IFN-g and PGE2

              Background The interest in the mechanisms involved in Toxoplasma gondii lipid acquisition has steadily increased during the past few decades, but it remains not completely understood. Here, we investigated the biogenesis and the fate of lipid droplets (LD) of skeletal muscle cells (SkMC) during their interaction with T. gondii by confocal and electron microscopy. We also evaluated whether infected SkMC modulates the production of prostaglandin E2 (PGE2), cytokines interleukin-12 (IL-12) and interferon-gamma (INF-g), and also the cyclooxygenase-2 (COX-2) gene induction. Methods Primary culture of skeletal muscle cells were infected with tachyzoites of T. gondii and analysed by confocal microscopy for observation of LD. Ultrastructural cytochemistry was also used for lipid and sarcoplasmatic reticulum (SR) detection. Dosage of cytokines (IL-12 and INF-g) by ELISA technique and enzyme-linked immunoassay (EIA) for PGE2 measurement were employed. The COX-2 gene expression analysis was performed by real time reverse transcriptase polymerase chain reaction (qRT-PCR). Results We demonstrated that T. gondii infection of SkMC leads to increase in LD number and area in a time course dependent manner. Moreover, the ultrastructural analysis demonstrated that SR and LD are in direct contact with parasitophorous vacuole membrane (PVM), within the vacuolar matrix, around it and interacting directly with the membrane of parasite, indicating that LD are recruited and deliver their content inside the parasitophorous vacuole (PV) in T. gondii-infected SkMC. We also observed a positive modulation of the production of IL-12 and IFN-g, increase of COX-2 mRNA levels in the first hour of T. gondii-SkMC interaction and an increase of prostaglandin E2 (PGE2) synthesis from 6 h up to 48 h of infection. Conclusions Taken together, the close association between SR and LD with PV could represent a source of lipids as well as other nutrients for the parasite survival, and together with the increased levels of IL-12, INF-g and inflammatory indicators PGE2 and COX-2 might contribute to the establishment and maintenance of chronic phase of the T. gondii infection in muscle cell.
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                Author and article information

                Contributors
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                Journal
                cr
                Ciência Rural
                Cienc. Rural
                Universidade Federal de Santa Maria
                1678-4596
                June 2016
                : 46
                : 6
                : 1053-1058
                Affiliations
                [1 ] Universidade Federal de Mato Grosso Brazil
                [2 ] Universidade Federal de Mato Grosso Brazil
                [3 ] Universidade Federal de Mato Grosso Brazil
                [4 ] Universidade Federal de Mato Grosso Brazil
                [5 ] Universidade Federal de Mato Grosso Brazil
                Article
                S0103-84782016000601053
                10.1590/0103-8478cr20151051
                25a14a16-7e20-4d42-b243-f318c9fa4bf0

                This work is licensed under a Creative Commons Attribution 4.0 International License.

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                SciELO Brazil

                Self URI (journal page): http://www.scielo.br/scielo.php?script=sci_serial&pid=0103-8478&lng=en
                Categories
                AGRONOMY

                Horticulture
                aqueous humor,intraocular inflammation,NSADs,toxoplasmosis,humor aquoso,inflamação intraocular,AINEs,toxoplasmose

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