Role of Ovarian Hormones in Psychological Stress-induced Oxidative Organ Damage in Rats

Yıl 2016, Cilt: 6 Sayı: 2, 72 - 79, 27.10.2016

Gülsün Memi Berrak Ç. Yeğen

Öz

Objective: Stress response varies with respect to gender via the hypothalamic–pituitary–gonadal axis. We aimed to investigate the effect of ovarian hormone deficiency on psychological stress response and oxidative damage.

 

Methods: Female Sprague Dawley rats (250–300 g, n=56) were divided as control, sham, and ovariectomy (OVX) groups. Sham operation or surgical OVX were conducted under anesthesia. After 60 days, the rats were placed in a special chamber to induce psychological stress by electric shock and were kept in the same chamber for 30 min on the following 3 days. Glucocorticoid receptor antagonist RU-486 (10 mg/kg), oxytocin receptor antagonist atosiban (1 mg/kg), or saline was intraperitoneally administered 10 min before stress exposure. After the hole-board anxiety test, the rats were decapitated on the 4th day; tissue and blood samples were obtained.

 

Results: Psychological stress increased cortisol levels in the RU-486-administered group, while cortisol levels were decreased in the atosiban-administered group. Serum interleukin (IL)-1β levels, but not TNF-α levels, were increased by inducing stress. Stress increased oxidative damage in the stomach, colon, and brain of ovariectomized rats (p<0.05–0.001), while atosiban partially reversed and RU-486 exaggerated oxidative damage. GSH levels that were depleted because of stress were partially replenished by administering atosiban; however, RU-486 had no effect on GSH levels.

 

Conclusion: Although the absence of ovarian hormones during psychological stress had no effect on cortisol or anxiety levels, changes in cytokine levels and oxidative tissue damage were observed.

Sıçanlarda Psikolojik Strese Bağlı Oksidan Doku Hasarında Over Hormonlarının Rolü

Öz

Amaç: Hipotalamus-hipofiz-gonad aksının etkisiyle, stres yanıtının cinsiyetler arasında farklılıklar gösterdiği bilinmektedir. Bu çalışmada postmenopozal dönemde over hormonlarının yokluğunun, psikolojik stres yanıtı ve oksidatif hasar üzerindeki rolünün araştırılması amaçlandı.

 

Yöntemler: Dişi Sprague-Dawley sıçanlar (250-300 g, n=56) kontrol, taklit cerrahi ve overektomi (OVX) olarak 3 gruba ayrıldı. Anestezi sonrası taklit cerrahi ve OVX işlemi uygulandı. Cerrahi işlemden 60 gün sonra psikolojik stres oluşturmak üzere sıçanlar elektrik şokunun uygulandığı özel bir bölmeye yerleştirildiler. Ardından 3 gün daha aynı bölmede, aynı süre ile şok uygulanmadan tutuldular. Stres uygulamalarının 10’ar dakika öncesinde sıçanlara intraperitoneal yolla glukokortikoid reseptör antagonisti RU-486 (10 mg/kg) veya oksitosin reseptör antagonisti atosiban (1 mg/kg) veya serum fizyolojik verildi. Dördüncü günde delikli levha testi uygulanmasını takiben sıçanlar dekapite edilerek, doku ve kan örnekleri alındı.

 

Bulgular: Psikolojik stres, RU-486 verilen gruplarda kortizol düzeylerini anlamlı olarak arttırırken atosiban verilen gruplarda azalttı. Stres uygulaması ile serum IL-1β düzeyleri artarken, serum TNF-α düzeylerinde değişiklik gözlenmedi. Stres, özellikle overektomi uygulanmış sıçanlarda mide, kolon ve beyin dokularında oksidatif hasarı arttırırken (p<0,05-0,001), RU-486’nın bu hasarı daha fazla arttırdığı, atosibanın ise bu etkiyi kısmen geri döndürdüğü gözlendi. Stres uygulaması ile azalan doku antioksidan miktarını RU-486 tedavisi değiştirmedi, ama atosiban kısmen arttırdı.

 

Sonuç: Çalışmanın bulguları, psikolojik stres durumunda over hormonlarının yokluğunun kortizol düzeyinde ya da anksiyete düzeyinde değişikliğe neden olmadığı halde, sitokin düzeylerinde ve dokuların oksidatif hasar durumlarında değişikliklere yol açabildiğini ortaya koymuştur.

Anahtar Kelimeler

Hipotalamus-hipofiz-adrenal bez aksı, hipotalamus-hipofiz-gonad aksı, glukokortikoid reseptörü, atosiban, oksitosin

Kaynakça

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