Duloksetinin Sıçan Uterus Düz Kasının Spontan ve Oksitosinle indüklenmiş Kasılmalarına Etkileri

Öz

Duloksetin (DX) depresyon, anksiyete ve diyabete bağlı nöropatik ağrılı hastaların tedavisinde kullanılmaktadır. Bununla birlikte kas ağrıları, kas sertliği ve kas krampları gibi yan etkileri de bulunmaktadır. Çalışmada in vitro olarak sıçan uterus kasına ait kasılma parametrelerine duloksetinin olası etkilerinin incelenmesi amaçlanmıştır. Çalışmada 16 yetişkin dişi sıçan basit randomizasyonla kontrol (n=8) ve DX (n=8) gruplarına ayrıldı. Ketamin-ksilazin anestezisi sonrası servikal dislokasyon ile sakrifiye edilen sıçanlardan uterus dokuları alınarak Krebs-Henseleit solüsyonuna aktarıldı. Dokular 20×3 mm longitudinal şeritler halinde hazırlanıp izole organ banyosu (İOB) sistemine yerleştirildi. Uyum süreci sonrası DX grubuna 1,5, 15, 30 ve 60 μM DX; kontrol grubuna ise eş hacimde çözücü uygulandı. Kasılmalar ayrıca 10⁻⁷ M oksitosin (OXT) ile indüklendi. Çözücü uygulamalarında gruplar arasında anlamlı fark saptanmadı (p>0,05); ancak en yüksek hacimde (V4) kasılma frekansı bazale göre azaldı (p=0,0282). DX (1,5–60 μM). Spontan uterus kasılmalarında kasılma kuvveti, AUC ve frekans parametrelerinde doz-bağımlı ve ileri düzeyde anlamlı inhibisyon oluşturdu (p<0,0001). Bu etki özellikle 60 μM dozda belirgin olup kasılma frekansı %28,45±8,63’e geriledi. Benzer şekilde DX, OXT ile indüklenen kasılmalarda da tüm parametrelerde doz-bağımlı ve anlamlı inhibisyon sağladı (p<0,0001). Yıkama sonrası kısmi iyileşme gözlenirken, aynı harfle gösterilen gruplar arasında anlamlı fark bulunmadı (p>0,05). DX, hem spontan hem de OXT ile indüklenen uterus düz kas kontraksiyonlarında doza bağımlı olarak azalma ve inhibisyona yol açmaktadır.

Anahtar Kelimeler

• duloksetin
• izole organ banyosu
• kasılma
• oksitosin
• sıçan
• uterus

Etik Beyan

Bu çalışmaya Necmettin Erbakan Üniversitesi Hayvan Deneyleri Yerel Etik Kurulu'nun 20.03.2025 tarihli, 2025-034 no.'lu kararının ardından başlanmıştır.

The Effects of Duloxetine on Spontaneous and Oxytocin-Induced Contractions of the Rat Uterine Smooth Muscle

Öz

Duloxetine (DX) is used in the treatment of depression, anxiety and diabetic neuropathic pain. However, It also has side effects such as muscle pain, stiffness and cramps. Therefore, this study aimed to investigate the possible effects of duloxetine on contractile parameters of rat uterine smooth muscle in vitro. Sixteen adult female rats were randomly assigned into control (n=8) and DX (n=8) groups. Following ketamine-xylazine anesthesia, rats were sacrificed by cervical dislocation, and uterine tissues were isolated and transferred into Krebs-Henseleit solution. Longitudinal uterine strips (20×3 mm) were mounted in an isolated organ bath (IOB) system. After the equilibration period, DX was administered cumulatively at concentrations of 1.5, 15, 30, and 60 μM, while the control group received equivalent volumes of vehicle. Contractions were also induced with 10⁻⁷ M oxytocin (OXT). Vehicle applications did not produce significant differences between groups overall (p>0.05); however, the highest volume (V4) significantly reduced contraction frequency compared to baseline (p=0.0282). DX (1.5–60 μM) caused a dose-dependent and highly significant inhibition in contraction force, AUC and contraction frequency during spontaneous uterine contractions (p<0.0001). This inhibitory effect was especially prominent at 60 μM, where contraction frequency decreased to 28.45±8.63%. Similarly, DX significantly and dose-dependently inhibited all parameters of OXT-induced contractions (p<0.0001). Partial recovery was observed after the washout period, and no significant differences were detected between groups indicated by the same letter (p>0.05). DX causes a dose-dependent reduction and inhibition in both spontaneous and OXT-induced uterine smooth muscle contractions.

Anahtar Kelimeler

• Duloxetine
• isolated organ bath
• contraction
• oxytocin
• rat
• uterus

Etik Beyan

This study was initiated following the approval of the Necmettin Erbakan University Animal Experiments Local Ethics Committee (decision no. 2025-034; approval date 20.03.2025).

Kaynakça

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