YAVUZ KÜRŞAD DAŞ, DİLEK GÜVENÇ, ABDURRAHMAN AKSOY, ENES ATMACA, OĞUZHAN YAVUZ

Tocolytic effects of meloxicam on ısolated cattle myometrium

Meloksikam seçici siklooksijenaz-2 (COX-2) enzim inhibitörü, steroid yapıda olmayan ağrı kesici ve yangı giderici ilaçların (NSAID) bir üyesidir. Bu çalışmada izole doku banyosunda önceden oksitosin (OT) ile uyarılmış inek miyometrium striplerine meloksikamın tokolitik (gevşetici) etkisi araştırılmıştır. Uterus örnekleri mezbahada iki yaşın üzerinde, yeni kesilen, anöstrüs evresinde gebe olmayan ineklerden sağlanmıştır. Çalışmada yedi örnek kullanılmış ve her örnek dört myometrium stripinden oluşturulmuştur. Örnekler spontan uterus kasılmaları şekilleninceye kadar doku banyolarında bekletilmiştir. Daha sonra her izole miyometrium üzerine 0.5 nM OT eklenmiştir. Bunu takiben 1x10-7 M ile 7x10-4 M arasında 10 farklı meloksikam (sodyum tuzu) dozu kümülatif olarak uygulanmıştır. Her uygulama sonrası uterus kasılmaları 20 dk süresince kaydedilmiştir. Uterus kasılmalarının grafiğinden ilaç etkisinin ölçüleri olan ortalama pik yükseklikleri (peak maximum, PMAX), frekans (dakikadaki pik atım sayıları, beats per minute-BPM) ve eğrinin altında kalan alan (EAA) değerleri hesaplanmıştır. Bunlara ek olarak meloksikamın tokolitik etkisinin etkili konsantrasyon 50 (EC50) değerleri GraphPad Prism (5.0) programı ile pik frekansları (BPM) için 4.22x10-4 M (2.63-6.76x10-4 M, % 95 güven aralığı, GA), EAA için 3.61x10-4 M (2.47-5.27x10-4 M, %95 GA) ve ortalama pik yükseklikleri (PMAX) için 2.31x10-4 M (1.97-2.70x10-4 M, %95 GA) olarak ölçülmüştür. Çalışma sonunda meloksikamın tokolitik olarak kullanımının, sığırlarda erken doğumu ve buna bağlı buzağı kayıplarını önleyebileceği kanısına varılmıştır. Bununla birlikte canlı sığırlar üzerinde meloksikamın klinik olarak tedavi edici etkilerinin yanı sıra; anne ve yavru üzerine olası istenmeyen etkilerini göstermek için in vivo çalışmaların yapılması gereklidir.

Anahtar Kelimeler:

oksitosin, yan etkiler, farmakokinetik, antienflamatuar ajanlar, sığır, kasılma, inek, miyometrium, steroit olmayan antienflamatuar ajanlar, farmakodinamik

Meloksikamın izole sığır miyometriumu üzerine tokolitik etkileri

Meloxicam is a selective, cyclooxygenase-2 (COX-2), enzyme inhibiting, non-steroid, and anti-inflammatory drug (NSAID). In this study, its tocolytic effects on the cattle myometrium strips pre-stimulated with oxytocin (OT) were investigated with the isolated tissue bath system. The uterine samples were from newly slaughtered, non-pregnant cattle which were older than two years old and in anoestrus stage at the time of sampling, in a registered slaughterhouse. Seven cattle samples (each sample consisted of four strips) were used in this study. The samples were incubated in the isolated tissue baths until regular spontaneous contractions occurred. 0.5 nM of OT was then applied to all strips. After OT application, 10 different doses of meloxicam (sodium salt) ranging between 1x10-7 and 7x10-4 M were administered, cumulatively. After each application, uterine contractions were recorded for 20 min. Mean peak amplitude (peak maximum, PMAX), frequency (beats per minute, BPM) and area under the curve (AUC) values of the uterine contractions, which were used to evaluate the effects of the drug, were calculated from the curve. In addition, the effective concentration 50 (EC50) values for the tocolytic effects of meloxicam were calculated 4.22x10-4 M (2.63-6.76x10-4 M, 95% confidence limits for mean, CLM) for frequency (BPM), 3.61x10-4 M (2.47-5.27x10-4 M, 95% CLM) for AUC and 2.31x10-4 M (1.97-2.70x10-4 M, 95% CLM) for peak amplitude (PMAX), by using the GraphPad Prism (5.0) program. At the end of this study, it is suggested that the use of meloxicam as a tocolytic agent may prevent preterm labour in cattle and the loss of calves. However, in vivo studies should be performed to show the clinical therapeutic and possible maternal and foetal adverse effects of meloxicam on live cattle.

Keywords:

oxytocin, adverse effects, pharmacokinetics, antiinflammatory agents, cattle, contraction, cows, myometrium, non-steroidal antiinflammatory agents, pharmacodynamics,

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