Efeito dos AINES na fertilidade, perda gestacional precoce e mobilidade embrionária de éguas receptoras de embrião
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Data
2017-07-11
Autores
Okada, Carolina Tiemi Cardoso [UNESP]
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Editor
Universidade Estadual Paulista (Unesp)
Resumo
A administração de antiinflamatórios não esteroides (AINEs) no momento da transferência de embrião em éguas é empregada usualmente para conter a inflamação uterina e produção de prostaglandina F2α (PGF2α), na tentativa de evitar a luteólise. No entanto, estes fármacos podem prejudicar a produção de prostaglandinas pelo concepto e alterar o mecanismo de mobilidade embrionária e reconhecimento materno fetal. Nesse estudo foi avaliada a ação do flunixin meglumine (FM) em um grande número de receptoras de embrião (n=409) em um centro comercial de reprodução equina, verificando estatisticamente a ação deste medicamento na taxa de prenhez e perda gestacional precoce. Os animais foram divididos em dois grupos (FM e controle), recebendo uma única aplicação de FM na dose de 1,1mg/kg imediatamente após a transferência de embrião em éguas alternadas para correta randomização. A taxa de prenhez aos 15 dias do grupo controle foi de 70,95% e a do grupo tratado 75,22%, sem diferença entre os grupos (p=0,3337). Aos 60 dias o grupo controle apresentou taxa de prenhez de 65,22% e o grupo tratado de 65,92%, sem diferença estatística (p>0,05). No entanto, foi observado que a perda embrionária até 60 dias do grupo controle foi 5,03% e no grupo tratado 10,0%, havendo tendência (p=0,0578) para perda gestacional precoce. Em um segundo experimento, AINEs de outras categorias como COX-2 seletivo: firocoxibe e COX-2 preferencial: Meloxicam foram determinados a fim de tentar estabelecer um tratamento antiinflamatório menos prejudicial à fase de mobilidade embrionária. A comparação dos AINEs foi mensurada de acordo com a quantidade de movimentos realizados pela vesícula embrionária após o pico de concentração plasmática de cada fármaco a partir de ultrassonografias seriadas. Os animais foram separados em 3 grupos de 10 éguas cada (flunixin meglumine, firocoxib e meloxicam) e, a partir da confirmação da gestação aos 12 dias, foram iniciadas ultrassonografias por meio de palpação retal a cada 5 minutos durante 1 hora com o propósito de mapear a localização do embrião e o número de seus movimentos. A segunda série de ultrassonografias foi realizada após o pico plasmático de cada AINE estabelecido por grupo e a terceira série após 24 horas da aplicação do fármaco. A dose para o FM foi de 1,1 mg/kg, para o firocoxib 0,2 mg/kg e para o meloxican 0,6 mg/kg. O grupo FM apresentou média de movimentos embrionários por hora de 5.8±0.3 durante o momento controle e depois do tratamento 2.3±0.5, correspondendo uma queda de 60%. No grupo que recebeu meloxicam o número de movimentos do embrião no momento controle foi de 5.9±0.3, diminuindo para 1.9±0.3 durante o pico sérico do medicamento, representando queda de 67%. Contudo, o firocoxib não modificou os padrões de movimentação embrionária da hora controle (5.7±0.4) para a hora após tratamento (5.8±0.3), sugerindo que o fármaco não interferiu com a mobilidade do concepto. Após 24 horas do tratamento todos os parâmetros de mobilidade estavam dentro da normalidade, indicando que não há efeito colateral permanente do FM e meloxicam. Em conclusão, o firocoxib foi o único AINE relatado nesse estudo que não alterou a mobilidade embrionária, sendo considerado mais seguro para ser administrado em éguas no início da gestação.
The administration of nonsteroidal anti-inflammatory drugs (NSAIDs) at the time of embryo transfer is usually used to inhibit uterine inflammation and prostaglandin F2α (PGF2α) production in an attempt to prevent luteolysis. However, these drugs may impair the production of prostaglandins by the conceptus and alter the mechanism of embryo mobility and maternal fetal recognition. In this study, the action of flunixin meglumine (FM) was evaluated in a large number of embryo recipients mares (n = 409) at a commercial center of equine reproduction, stating the action of this drug on the pregnancy rate and early pregnancy loss. The animals were divided into two groups (FM and control), receiving a single FM application at the dose of 1.1mg / kg immediately after the embryo transfer in alternate mares for correct randomization. The pregnancy rate at 15 days in the control group was 70.95% and 75.22% on the treated group, with no difference between groups (p = 0.3337). At 60 days the control group presented a pregnancy rate of 65.22% and the treated group of 65.92%, with no statistical difference (p > 0.05). Nevertheless, it was observed that the pregnancy loss up to 60 days in the control group was 5.03% and in the treated group 10.0%, with a trend (p = 0.0578) to early pregnancy loss. In a second experiment NSAIDs of other categories as selective COX-2: firocoxib and preferential COX-2: meloxicam were determined in order to try to establish an anti-inflammatory treatment less damaging to the stage of embryonic mobility. The comparison of NSAIDs was measured according to the number of movements performed by the embryonic vesicle after the peak plasma concentration of each drug beginning at serial ultrasonography. The animals were separated into 3 groups of 10 mares each (flunixin meglumine, firocoxib and meloxicam) and from the confirmation of pregnancy at 12 days, ultrasonography was started by rectal palpation every 5 minutes during 1 hour for mapping the location of the embryos and the number of its movements. The second series of ultrasound was performed after each NSAID peak plasma established per group and the third series was performed after 24 hours after application of the drug. For FM, a therapeutic dose of 1.1 mg/kg was used, for firocoxib the dose was 0.2 mg/kg and for meloxican the dose was 0.6 mg/kg. The FM group showed average of embryonic movements per hour of 5.8 ± 0.3 for the time control and after treatment 2.3 ± 0.5, representing a decrease of 60%. In the group receiving meloxicam the number of movements of the embryo at the time of the control was 5.9 ± 0.3, decreasing to 1.9 ± 0.3 during the serum peak of the drug, representing a reduction of 67%. However, firocoxib did not modify the patterns of embryonic movement of the control hour (5.7 ± 0.4) for the hour after treatment (5.8 ± 0.3), suggesting that the drug did not interfere with the conceptus mobility. After 24 hours of treatment all mobility parameters were within normal range, indicating that there is no permanent side effect of FM and meloxicam. In conclusion, firocoxib was the only NSAID reported in this study that did not alter embryonic mobility, being considered safer to be administered in mares at the beginning of gestation.
The administration of nonsteroidal anti-inflammatory drugs (NSAIDs) at the time of embryo transfer is usually used to inhibit uterine inflammation and prostaglandin F2α (PGF2α) production in an attempt to prevent luteolysis. However, these drugs may impair the production of prostaglandins by the conceptus and alter the mechanism of embryo mobility and maternal fetal recognition. In this study, the action of flunixin meglumine (FM) was evaluated in a large number of embryo recipients mares (n = 409) at a commercial center of equine reproduction, stating the action of this drug on the pregnancy rate and early pregnancy loss. The animals were divided into two groups (FM and control), receiving a single FM application at the dose of 1.1mg / kg immediately after the embryo transfer in alternate mares for correct randomization. The pregnancy rate at 15 days in the control group was 70.95% and 75.22% on the treated group, with no difference between groups (p = 0.3337). At 60 days the control group presented a pregnancy rate of 65.22% and the treated group of 65.92%, with no statistical difference (p > 0.05). Nevertheless, it was observed that the pregnancy loss up to 60 days in the control group was 5.03% and in the treated group 10.0%, with a trend (p = 0.0578) to early pregnancy loss. In a second experiment NSAIDs of other categories as selective COX-2: firocoxib and preferential COX-2: meloxicam were determined in order to try to establish an anti-inflammatory treatment less damaging to the stage of embryonic mobility. The comparison of NSAIDs was measured according to the number of movements performed by the embryonic vesicle after the peak plasma concentration of each drug beginning at serial ultrasonography. The animals were separated into 3 groups of 10 mares each (flunixin meglumine, firocoxib and meloxicam) and from the confirmation of pregnancy at 12 days, ultrasonography was started by rectal palpation every 5 minutes during 1 hour for mapping the location of the embryos and the number of its movements. The second series of ultrasound was performed after each NSAID peak plasma established per group and the third series was performed after 24 hours after application of the drug. For FM, a therapeutic dose of 1.1 mg/kg was used, for firocoxib the dose was 0.2 mg/kg and for meloxican the dose was 0.6 mg/kg. The FM group showed average of embryonic movements per hour of 5.8 ± 0.3 for the time control and after treatment 2.3 ± 0.5, representing a decrease of 60%. In the group receiving meloxicam the number of movements of the embryo at the time of the control was 5.9 ± 0.3, decreasing to 1.9 ± 0.3 during the serum peak of the drug, representing a reduction of 67%. However, firocoxib did not modify the patterns of embryonic movement of the control hour (5.7 ± 0.4) for the hour after treatment (5.8 ± 0.3), suggesting that the drug did not interfere with the conceptus mobility. After 24 hours of treatment all mobility parameters were within normal range, indicating that there is no permanent side effect of FM and meloxicam. In conclusion, firocoxib was the only NSAID reported in this study that did not alter embryonic mobility, being considered safer to be administered in mares at the beginning of gestation.
Descrição
Palavras-chave
Antiinflamatório não esteroide, Ciclooxigenase, Transferência de embrião, Reconhecimento materno da gestação, Non-steroidal anti-inflammatory, Embryo transfer, Embryo mobility, Cyclooxygenase