STANOZOLOL UYGULANAN SIÇAN BÖBREĞİNDE PTEN VE PI3K/AKT EKSPRESYONLARININ DEĞERLENDİRİLMESİ

Amaç: Stanozolol, gençler ve sporcular tarafından vücut geliştirme, spor ve atletizmde yaygın kullanımı olan bir anabolik androjenik steroiddir (AAS). Stanozololün böbrek fonksiyonlarındaki potansiyel etkileri tanımlanmamıştır. Bu çalışmada, stanozolol ile tedavi edilen sıçan böbreklerinde tümör baskılayıcı protein fosfotaz tensin homolog (Pten), Phosphatidylinositol-3-kinase (Pi3k) ve protein kinaz B (Akt1)’nin mRNA düzeylerinin ekspresyonunu araştırdık. Gereç ve Yöntem: Sıçanlar, kontrol, çözücü kontrol, steroid, çözücü kontrol egzersiz, steroid egzersiz olarak 5 gruba ayrıldı. Yirmi sekiz gün boyunca subkutan stanozolol enjeksiyonu (5 mg/ kg) uygulandı ve egzersiz gruplarındaki hayvanlara 20 dk/gün, 5 gün/hafta yüzme egzersizleri yaptırıldı. PTEN ekspresyonu immünohistokimya ile değerlendirildi. Ayrıca Pten, Pi3k ve Akt1 mRNA ekspresyonları RT-PCR yoluyla analiz edildi. Bulgular: Kontrol, çözücü kontrol ve çözücü kontrol egzersiz gruplarındaki mezanjiyal hücreler ve böbrek tübülleri, steroid grubunda saptanan zayıf PTEN reaktivitesine karşı güçlü (+++) PTEN reaktivitesi gösterdi. Steroid egzersiz grubunun mezanjiyal ve tübül hücrelerinde orta düzeyde PTEN reaktivitesi saptandı. Pten mRNA ekspresyonu, steroid grubunda kontrol ve diğer gruplara göre anlamlı düşüş gösterdi, Pi3k ve Akt1 mRNA ekspresyonu anlamlı olarak arttı (p <0.001). Egzersiz tedavisi ile Pten ekspresyonu artış, Pi3k ve Akt1 ekspresyonu azalma gösterdi (p<0.05). Sonuç: Bulgularımız, AAS kullanımının, artan Pi3k ve Akt1 mRNA seviyeleri ile ilişkili olabilecek böbreklerde PTEN ekspresyonunu inhibe edebileceğini düşündürmektedir. AAS kullanımı ile yapılan egzersiz, PTEN ekspresyon seviyelerinin artması ve Pi3k ve Akt1 seviyelerinin düşmesi nedeniyle stanozolole maruz kalan böbrekler üzerinde koruyucu olabilir.

Anahtar Kelimeler:

Stanozolol, Böbrek, PTEN, PI3K, Akt1

EVALUATION OF PTEN AND PI3K/AKT EXPRESSIONS IN STANOZOLOL-TREATED RAT KIDNEYS

Objective: Stanozolol is an anabolic androgenic steroid (AAS) that is widely used by teenagers and athletes in bodybuilding, sports, and athletics. The potential effects of stanozolol in kidney functions have not been defined. In this study we investigated the expression of tumor suppressor protein phosphatase and tensin homolog (Pten) and mRNA levels of phosphatidylinositol 4,5-bisphosphate 3 kinase (Pi3k) and the protein kinase B (Akt1) signaling pathway in rat kidneys treated by stanozolol. Materials and Methods: Rats were randomized to 5 groups as control, solvent control, steroid (stanozolol), solvent-exercise, and steroid-exercise. Subcutaneous injection of stanozolol (5 mg/kg) was applied for 28 days and swimming exercise was performed 20 min/day, 5 days/week in exercise groups. Expression of PTEN was evaluated by immunohistochemistry. Also, Pten, Pi3k, and Akt1 mRNA expressions were analyzed via RT-PCR. Results: Mesangial cells and renal tubules in the control, solvent control, and solvent exercise groups showed strong (+++) PTEN reactivity against weak PTEN reactivity in the steroid group. Moderate PTEN reactivity was detected in cells of the steroid exercise group. Pten mRNA expression was significantly decreased, and Pi3k and Akt1 mRNA expression were significantly increased in the steroid group versus other groups (p<0.001). Pten expression showed increase while Pi3k and Akt1 expression showed decrease with exercise treatment (p<0.05). Conclusion: Our findings suggest that AAS usage may inhibit PTEN expression in kidneys, which can be associated with increased Pi3k and Akt1 mRNA levels. Exercise performed with AAS usage can be protective on stanozolol-exposed kidneys due to increased levels of PTEN expression and decreased levels of Pi3k and Akt1.

Keywords:

Stanozolol, Kidney, PTEN, PI3K, Akt1,

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