Erkan TUNCAY, Makbule Fulya TUTAR, Belma TURAN, İsmet AYDIN, Muhammet DOĞAN, Ay?egül TOY, Yusuf OLGAR, Esma Nur OKATAN, Sinan DEĞİRMENCİ, Seyfullay AKSU, Emrullah BIÇAKÇI, Ahmet GÜNDÜZ

Pioglitazonun Metabolik Sendromlu Sıçan Kalp Fonksiyonuna Etkisinin Elektrofizyolojik Yöntemlerle İncelenmesi

Amaç: Metabolik sendrom (MetS), genellikle insülin-direnci ile karakterize, kardiyovasküler sistem sorunlarıyla seyreden, mekanizması henüz tam olarak anla?ılamamı? bir hastalıktır. Diğer yandan, MetS-indüklü komplikasyonların tedavisinde kullanılan bazı ilaçların, kardiyovasküler sistem sorunlarına ek sorunlar getirebildiği tartı?ılmaktadır. Bu çalı?mada, ilk olarak insülin-duyarla?tırıcı olarak bilinen pioglitazonun, MetSindüklü bozulan kalp fonksiyonu üzerindeki etkisini incelemeyi hedefledik. İkinci olarak, MetS-indüklü etkinin artan oksidatif stres üzerinden olup olmadığını göstermek amacıyla, bilinen bir antioksidan (kuersetin) uygulayarak sonuçları kar?ıla?tırmalı olarak incelenmesi hedefledik. Materyal ve Metodlar: Toplam 28-adet erkek Wistar-türü sıçanlar (3 aylık), kontrol grubu (Kon), MetS grubu (MetS; 18-hafta içme suyuna %32 sükroz eklenerek olu?turulmu?tur), MetS-grubunun 16. haftasından itibaren 2-hafta süre ile ya pioglitazon uygulanmı? MetS-grubu (Piog; 30 mg/kg/gün), ya da kuersetin uygulanmı? MetS grubu (Kuer; 75 mg/kg/gün) olarak düzenlenmi?tir. Tüm hayvanlar standart ko?ullarda normal sıçan yemi ile beslenmi?tir. Çalı?ma sonunda, hayvanların vücut ağırlıkları, kan ?ekeri ile serum toplam oksitatif stres (TOS) ve antioksidan (TAS) durumları özel kit ile ölçülmü?tür. Langendorff-izole-organ-sisteminde sol ventrikül içi basınç deği?imleri (SVBD) ile, enzimatik yöntemle kalbin ventrikülünden izole edilen kardiyomiyositlerde (Ca2+-duyarlı florofor Fura-2AM ile boyanmı?) hücre-içi bazal serbest-Ca2+ seviyesi ([Ca2+]i) ve elektriksel-uyarı altında (aksiyon-potansiyeli sırasında) geçici [Ca2+]i deği?imleri incelenmi?tir. Bulgular ve Sonuç: Pioglitazon veya kuersetin, MetS-grubunda kilo artı?ı ve yüksek kan ?ekeri üzerinde pozitif etkiler gösterirken, her iki ajan artmı? olan serum TOS seviyelerini deği?tirememi?, buna kar?ılık küçük fakat anlamlı seviyede TAS seviyesinin yükselmesine neden olmu?lardır (p

An Investigation on Effects of Pioglitazone in the Heart Function from Rats with Metabolic Syndrome by Using Electrophysiological Techniques

Objective: Metabolic syndrome (MetS), generally characterized with insulin-resistance, leads to severe cardiovascular disorders, however, the underlying mechanisms of this syndrome has not yet been fully determined. In addition, there are some controversies related with unti-diabetic agents used for treatment of MetS-induced complications, including their aggravating effects on the depressed cardiac function. Therefore, in this study, we first aimed to investigate the effects of pioglitazone, known as a insulinsensitizer, on MetS-induced heart dysfunction. Second, for a comparative study to determine whether MetS-induced heart dysfunction is due to increased oxidative stress, we used a known antioxidant (quercetin) to MetS rats for the same period. Material and Methods: Total 28 male Wistar rats (3 months) were grouped as control group, (Con), MetS group (MetS; added 32% sucrose to drinking water for 18-week), MetS group supplemented with pioglitazone (Piog; 30 mg/kg/day via gavage for 2-week, from 16th-week of MetS-group) and MetS with quercetin (Quer; 75 mg/kg/day via gavage for 2-weeks from 16th-week of MetS group). All rats were fed with standard rat-diet and tap water at standard condition. At the end of experimental period, the body weights and blood glucose levels, and total oxidative status (TOS) and total antioxidant status (TAS) in serum by using special kits were measured for all animals. By using Langendorff-isolated-organ system, left ventricle pressure changes (LVPC) were measured in isolated hearts. The basal level of intracellular free Ca2+ ([Ca2+]i) and Ca2+ transients under electrical-situmulation (under action-potential) were measured in freshly isolated cardiomyocytes by enzymatic-method (loaded with Ca2+-sensitive fluorescence dye, Fura-2AM). Results and Discussion: Either pioglitazone or quercetin application have positive effects on body weight and high blood sugar levels in MetS-group rats. Additionally, both agents caused a small but significant increase on serum TAS levels (p

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