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

Tocolytic effects of diclofenac potassium and diclofenac sodium on cattle myometrium pre-incubated with PCB-153

Bu çalışmada, steroid yapıda olmayan ağrı kesici ve yangı giderici ilaçlardan (non steroidal anti-inflammatory drugs, NSAIDs) diklofenakın potasyum ve sodyum tuzlarının poliklorlu bifenil (PCB)lerden östrojenik etkili 2,2,4,4,5,5-hekzaklorobifenil (PCB-153) varlığında sığır uterus düz kaslarını gevşetici etkisi araştırılmıştır. Uterus örnekleri mezbahada iki yaşın üzerinde, yeni kesilen, anöstrüs evresinde, gebe olmayan ineklerden sağlanmıştır. İlaçların etkisini ortaya koymak için, dört kontrol (diklofenak potasyum 24 ve 48 saat, diklofenak sodyum 24 ve 48 saat) ve dört PCB-153 (diklofenak potasyum 24 ve 48 saat, diklofenak sodyum 24 ve 48 saat) olmak üzere sekiz ayrı grup oluşturulmuştur. Her bir grup iki farklı hayvandan dörder olmak üzere toplam sekiz miyometrium şeridi içermektedir. Kontrol grupları ayrı ayrı 24 ve 48 saat süre ile fizyolojik tuz solüsyonu (physiological salt saline, PSS) içinde, PCB-153 grupları ise aynı sürelerle 100 ng/mL PCB-153 içeren PSS içinde bekletilmiştir. Bu süreler sonrasında miyometrium şeritleri izole doku banyosu sistemine asılarak spontan kasılmalar oluşuncaya kadar beklenmiştir. Tüm gruplara spontan kasılmaları teşvik etmek amacı ile 0.5 nM yoğunluğunda oksitosin (OT) uygulanmıştır. Daha sonra diklofenak potasyum ve diklofenak sodyum kendileri için oluşturulan kontrol ve PCB-153 gruplarına 1x10-7 ve 7x10-4 M arası yoğunluklarda en yüksek inhibitör etki görülünceye kadar kümülatif olarak uygulanmıştır. Her uygulama sonrası uterus kasılmaları 20 dk süre ile kaydedilmiştir. Elde edilen grafiklerden ilaç etkisinin ölçütleri olan ortalama pik yükseklikleri (PMAX), frekansları (dakikadaki pik sayısı, beats per minute-BPM) ve eğrinin altında kalan alan (EAA) değerleri hesaplanmış ve istatistiksel olarak değerlendirilmiştir. Ayrıca miyometrium kasılmalarının BPM, PMAX ve EAA değerleri için inhibitör yoğunluk 50 (IC50) değerleri hesaplanmıştır. Çalışma sonunda diklofenak potasyum ve diklofenak sodyumun önceden PCB-153 ile inkübe edilen sığır miyometrium şeritleri üzerine tokolitik etkisi ortaya konmuştur.

Anahtar Kelimeler:

farmakokinetik, farmakoloji, potasyum, sodyum, sığır, kasılma, miyometrium, steroit olmayan antienflamatuar ajanlar, farmakodinamik

PCB-153 İle inkübe edilen sığır miyometriumu üzerine diklofenak potasyum ve diklofenak sodyumun tokolitik etkisi

In this study, the tocolytic effects of the potassium and sodium salts of diclofenac, a non-steroidal anti-inflammatory drug (NSAID), on cattle myometria were investigated in the presence of an estrogenic polychlorinated biphenyl congener 2,2,4,4,5,5-hexachlorobiphenyl (PCB-153). The uterine samples were obtained from newly slaughtered, non-pregnant cattle more than two years old and in the anoestrus stage. Eight groups were constituted for testing (each group contained 8 strips from two animals, with 4 from each); there were four control groups (diclofenac potassium 24 h and 48 h; diclofenac sodium 24 h and 48 h) and four groups for PCB-153 (diclofenac potassium 24 h and 48 h; diclofenac sodium 24 h and 48 h). The control groups were incubated in physiological salt solution (PSS) for 24 or 48 hours and the PCB-153 groups were incubated in PSS which contained 100 ng/mL of PCB-153, for either 24 h or 48 h. After the incubation period, the strips were hung and incubated in the tissue bath system until spontaneous contractions occurred. Oxytocin (OT) was administered at 0.5 nM to the strips in all groups for the stimulation of spontaneous contractions. Diclofenac potassium and diclofenac sodium were then administered cumulatively in the range of 1x10-7 to 7x10-4 M to the strips of all groups to the maximum inhibitory effect was observed. After each application, isometric uterine contractions were recorded for 20 min. Mean peak amplitude (PMAX), frequency (beats per minutes, BPM) and area under the curve (AUC) values of the myometrial contractions, which are criteria for determining drug effects, were calculated from the curve and evaluated statistically. The inhibitory concentration 50 (IC50) values were calculated for the BPM, PMAX and AUC values of the myometrial contractions. Finally, the tocolytic effects of diclofenac potassium and diclofenac sodium on the contractions of cattle uterine strips pre-incubated with PCB-153, were determined.

Keywords:

pharmacokinetics, pharmacology, potassium, sodium, cattle, contraction, myometrium, non-steroidal antiinflammatory agents, pharmacodynamics,

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