Ceylan Verda BİTİRİM, Yusuf OLGAR, Deniz BİLLUR, Kamil AKÇALI, Belma TURAN

İnsülin-dirençli Memeli Kalp Fonksiyon Bozukluğunda Mitokondrihedefli Antioksidan Mitotempo Uygulamasının Pozitif Etkileri

Amaç: Karbonhidrat ve/veya yağ ağırlıklı beslenme bireylerde insülin direnci ile karakterize metabolik sendrom (MetS) gelişmesine neden olmaktadır. Yaşam süresinin uzaması da toplumlarda ileri yaş grubu oranının hızla yükselmesi ile sonuçlanmakta ve yaşlanan popülasyonun önemli bir oranında ise insülin direnci gelişebilmektedir. İnsülin direnci ve kalp fonksiyonu bozukluğu arasında en azından reaktif oksijen türlerinin kontrolsüz üretimi yoluyla yakın ilişki olduğu ve bu ilişkide mitokondri bozulmasının rol oynadığı ileri sürülmektedir. Bu nedenle bu çalışmada, izole sıçan kardiyomiyositlerinde mitokondriyon-hedefli bir antioksidan uygulamasının olası pozitif etkilerinin elektrofizyolojik ve histolojik olarak incelenmesi hedeflenmiştir. Gereç ve Yöntem: Çalışmada 24 aylık Wistar türü erkek sıçanlar (yaşlı grup; 7 adet), %32 oranında sukroz-beslenmesi ile MetS-grup oluşturulan erişkin (6 aylık; 7 adet) ve standart yemle beslenen erişkin (kontrol grup; 6 aylık ve 7 adet) sıçanlar kullanılmıştır. MetS, yüksek kan şekeri, oral glikoz tolerans testi ve serum insülin seviyeleri ile doğrulandı. Sol ventrikülden enzimatik yolla hücre izole edilerek, mitokondriyonların yapısal incelemeleri, hücrelerde fonksiyonel parametreler ve adenozin trifosfat (ATP)-duyarlı K+-kanal akımları (IKATP) (patch-clamp ile) incelenmiştir. Bulgular: İnsülin direnci gelişen sıçan kardiyomiyositlerinde, mitokondride fragmantasyonun arttığı, mitokondriyon-membran-potansiyelinin depolarize olduğu ve reaktif oksijen türleri miktarının arttığı gözlenmiştir. Yaşlı-sıçan kardiyomiyositlerinde IKATP’nin deprese olduğu (p

Beneficial Effect of a Mitochondrial-targeted Antioxidant Mitotempo in Insulin-resistant Mammalian Cardiac Dysfunction

Objectives: Overfeeding with a high carbohydrate and/or high-fat diet induces metabolic syndrome (MetS) in humans, which is characterized by insulin-resistance. Long life span leads to increases in the ratio of aged humans in populations and an important percentage of the aged humans has insulin-resistance. There is a close relationship between insulin resistance and cardiac dysfunction, at least, via uncontrolled production of reactive oxygen species, while mitochondrial dysfunction plays an important role in that relation. To explore that relation, we aimed to examine the possible cardioprotective effect of a mitochondria-targeting antioxidant by using electrophysiological and histological examinations. Materials and Methods: We used Wistar male rats in three groups as; those that were 24-month-old (elderly group; n=7), adults fed with 32% sucrose diet (MetS-group; 6-month-old; n=7), and adults fed with standard food (Control group; 6-month-old, n=7). MetS was confirmed with high blood glucose, oral glucose tolerance test, and serum insulin levels. Cardiomyocytes either treated with an antioxidant MitoTEMPO were isolated from the left ventricle by enzymatic method, and the ultrastructure and function of mitochondria as well as adenosine triphosphate (ATP)- dependent K+-channel currents (IKATP; patch-clamp technique) were evaluated. Results: There were marked increases in the fragmentation of mitochondria, depolarization in the membrane potential, and the production of ROS in insulin-resistant cardiomyocytes. There were significant decreases in IKATP and ATP level (p

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