Öz
Amaç
Doksorubisin (DOX), oksidatif ve endoplazmik retikulum (ER) stresi yoluyla kardiyotoksisiteye neden olur. Bu çalışma, ER stresi ve SIRT1 sinyaline odaklanarak, sıçanlarda DOX’in neden olduğu kalp hasarına karşı quercetinin kardiyoprotektif etkilerini değerlendirmiştir.
Yöntem
Wistar Albino sıçanlar kullanılmıştır. Sıçanlar kontrol, DOX, düşük doz quercetin (10 mg/kg) + DOX ve yüksek doz quercetin (100 mg/kg) + DOX gruplarına ayrılmıştır. Kardiyak fonksiyon II elektrokardiyografi ile değerlendirilirken, miyokardiyal hasar Tc-99m pirofosfat (PYP) sintigrafisi kullanılarak değerlendirilmiştir. Kardiyak biyobelirteçler, enflamatuvar sitokinler, oksidatif stres parametreleri, ER stres belirteçleri ve SIRT1 ekspresyonu analiz edildi.
Bulgular
DOX, Q dalgası-T dalgası aralığı uzaması ve ST segment yükselmesi, miyokardiyal 99mTc-PYP alımında artış, kardiyak hasar biyobelirteçlerinde, böbrek ve karaciğer belirteçlerinde yükselme, oksidatif stres artışı, enflamatuvar yanıtlarda (tümör nekroz faktörü-α, interlökin-6) artış, GRP78 ve C/EBP homolog proteinin yukarı regülasyonu ve SIRT1 ve glutatyonun baskılanması (p<0,05) gibi belirgin elektrokardiyografi anormalliklerine neden olmuştur. Quercetin, bu değişiklikleri doz bağımlı bir şekilde önemli ölçüde azalttı ve daha yüksek dozda daha fazla koruma gözlendi.
Sonuç
Quercetin, SIRT1 sinyalini geri yükleyerek oksidatif stresi, ER stresini ve enflamasyonu baskılayarak DOX'in neden olduğu kardiyotoksisiteyi hafifletir. Elektrokardiyografi ve Tc-99m PYP sintigrafisinin entegrasyonu, quercetinin kardiyoprotektif etkilerine ilişkin yeni multimodal kanıtlar sağlar.
Anahtar Kelimeler:
Doksorubisin, ER stresi, kardiyotoksisite, oksidatif stres, quercetin, sintigrafi
Kaynaklar
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