Objevtive: The present study was designed to examine the effects of high dose and low dose duloxetine on Cx43, a gap junction (GJ) protein; on S100A, cardiac contractility component and on certain early cardiac impairment parameters as TnI and TnT. Material and Methods: The study was performed with 24 male Wistar Albino rats by generating control group (1 ml solvent), low-dose duloxetine (LDD) group (10 mg/kg) and high-dose duloxetine (HDD) group (100 mg/kg). After the experimental procedure, the results concerning blood pressure and heart rates of the anesthetized rats were recorded and HE staining and immunostaining of Cx43, S100A, TnI and TnT were applied to the heart tissue sections. Results: In the control group, Cx43 was stained as marked streaks between cardiomyocytes; TnI, TnT and S100A were stained as homogenous and dark brown in cytoplasm. Nevertheless, intensity of Cx43 immunostaining showed significant increase in duloxetine- treated groups (p0.05). Conclusion: Our study reveals that duloxetine induced an increase in the immunostaining of Cx43, and a decrease in the immunostaining of TnI, TnT and S100A, also known as early cardiac parameters. Furthermore, duloxetine was observed to show no effect on oxidant and antioxidant parameters. While heart rate remained unchanged, mean blood pressure decreased in high dose duloxetine group. In the light of the study outcomes, it has been concluded that antidepressants must be administered more advertently in depression patients with heart disorders.
Keywords: Rat; heart; antidepressant; duloxetine; immunohistochemistry
Amaç: Bu çalışmada düşük ve yüksek doz duloksetinin, gap junction bileşenlerinden Cx43, kardiyak kontraktilite komponenti S100A ve kardiyak kasılma belirteci olarak kullanılan TnI ve TnT gibi erken kardiyak hasar parametreleri üzerindeki etkilerinin değerlendirilmesi amaçlanmaktadır. Gereç ve Yöntemler: Wistar Albino cinsi 24 adet erkek sıçan; kontrol (1 ml çözücü), düşük doz duloksetin (DDD) (10 mg/kg) ve yüksek doz duloksetin (YDD) (100 mg/kg) şeklinde üç gruba ayrıldı. Deney protokolü bitiminde anestezi altındaki sıçanların kan basıncı ile kalp hızı sonuçları kaydedildi ve elde edilen doku kesitlerine H-E boyama yöntemi, Cx43, S100A, TnI ve TnT immün boyama yöntemleri uygulandı. Bulgular: Kontrol grubunda Cx43 kardiyomiyositlerin bağlantı bölgelerinde belirgin çizgilenmeler şeklinde, TnI, TnT ve S100A ise sitoplazma içerisinde homojen ve koyu kahverengi olarak boyandı. Diğer yandan, duloksetin uygulanan gruplarda Cx43 immünreaktivite şiddetinde artış gözlendi (p0,05). Sonuç: Çalışmamız duloksetinin erken kardiyak hasar parametreleri olarak bilinen Cx43 immünoreaktivesinde artışa, TnI, TnT ve S100A'da ise azalmaya neden olduğunu gösterdi. Ayrıca oksidan- antioksidan parametreler ile kalp hızı üzerine herhangi bir değişikliğe neden olmadığı, ancak doza bağlı olarak ortalama kan basıncını azalttığı gözlendi. Bütün bunlar göz önüne alınarak, kalp rahatsızlığı olan depresyon hastalarında, antidepresanların da daha dikkatli uygulanması gerektiği sonucuna varıldı.
Anahtar Kelimeler: Sıçan; kalp; antidepresan; duloksetin; immünohistokimya
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