Klorokuin Endoplazmik Retikulum Stresini ve Enflamasyonu İnhibe Ederek Sıçanlarda Adriamisin Uyarılı Kardiyotoksisiteyi Engeller

Year 2020, Volume: 77 Issue: 4, 459 - 466, 01.12.2020

Emin Kaymak Ali Tuğrul Akın Emel Öztürk Tayfun Ceylan Nurhan Kuloğlu Derya Karabulut Birkan Yakan

Abstract

Amaç: Adriamisin ADR kanser türlerinde kullanılan kemoterapötik bir ilaç olarak bilinmektedir. ADR uyarılı kardiyomiyopati toksik özelliğinden dolayı ilacın kullanımını zorlaştırmaktadır. ADR uyarılı kardiyotoksisitede enflamasyon ve endoplazmik retikulum stresi ERs artmaktadır. Pek çok kanser türünde kullanılan kemoterapötik ilaç olan ADR’nin yol açtığı kardiyotoksisiteye karşı sıtma ilacı olan klorokuin CLQ kullanımının ERs ve enflamasyon üzerinden koruyucu etkilerinin araştırılması amaçlandı. Yöntem: Sıçanlar rastgele 4 gruba ayrıldı: Kontrol grubu n = 8 dışındakilere, CLQ n = 8 günde 50 mg/kg intraperitoneal i.p. , ADR n = 8 2 mg/kg i.p. olarak her 3 günde bir, ADR + CLQ grubuna da n = 8 2mg/kg i.p. ADR + 50 mg/kg i.p. CLQ uygulandı. Deney toplam 30 gün sürdü. Deneyin sonunda, sıçanlar sakrifiye edildi ve kalp dokuları inceleme için hayvanlardan çıkarıldı. Kalp dokularındaki histopatolojik değişiklikler değerlendirildi ve ERs’yi belirlemek için Glukoz düzenleyici protein GRP78 antikoru ve enflamasyon için tümör nekroz faktörü-α TNF-α antikoru ile immün boyama yapıldı. Fotoğraflar Olympus BX53 mikroskobu ile çekildi analiz edildi.Bulgular: ADR grubunun kontrol grubuna kıyasla histopatolojik bozulma gösterdiğini ve CLQ tedavisinin ADR tarafından indüklenen bu hasarı iyileştirdiği gözlemlendi. ADR grubunda GRP78 ve TNF-α immünoreaktivitesinde kontrol grubuna göre artış vardı p

Keywords

Adriamisin, klorokuin, kalp, endoplasmik retikulum stresi, enflamasyon

Chloroquine Inhibits Adriamycin-Induced Cardiotoxicity İn Rats By Inhibiting Endoplasmic Reticulum Stress And Inflammation

Abstract

Objective: Adriamycin ADR is known as a chemotherapeutic drug used in cancer types. ADRinduced cardiomyopathy makes it difficult to use the drug due to its toxic properties. Inflammation and ER stress increase in ADR-induced cardiotoxicity. The aim of this study was to investigate the protective effects of chloroquine CLQ , a malaria medication used in many types of cancer, against the cardiotoxicity caused by ADR on endoplasmic reticulum stress and inflammation.Methods: Rats were randomly divided into 4 groups: Control n = 8 , CLQ n = 8 50 mg/kg intraperitoneal i.p. daily, ADR n = 8 2 mg/kg i.p. every 3 days, ADR + CLQ n = 8 2mg/kg i.p. ADR + 50 mg/kg i.p. CLQ. The experiment lasted a total of 30 days. At the end of the experiment, the rats were sacrificed and the heart tissues were removed from the animals for examination. Histopathological changes in the heart tissues were evaluated and immune staining was performed with Glucose-regulated protein 78 GRP78 antibody and tumor necrosis factor-α TNF-α antibody for inflammation to determine endoplasmic reticulum stress. Photos were taken with Olympus BX53 microscope and analyzed.Adriamisin ADR pek çok kanser tedavisinde kullanılan kuvvetli bir terapötik maddedir 1 . ADR solid ve hemotopoetik tümörlerin tedavisinde kullanılan antrasiklin bir ilaçtır 2 . İlaç kanser hücrelerinde bu özelliğini topoizomeraz II ile DNA hasarının başlatılması ve apoptozisi gibi süreçlerle yapmaktadır 3 . İlaç klinikte kullanılmasına rağmen yan etkieri de bulunmaktadır. Kanser hastalarında ADR kullanımı arasında böbrek, karaciğer, testis ve kalp gibi önemli organlarda hasara yol açmaktadır . ADR uyarılı kardiyomiyopati toksik özelliğinden dolayı ilacın kullanımını sınırlandırmaktadır 8 . ADR uyarılı kardiyotoksisiteye birçok mekanizma karışmaktadır. ADR kardiyomiyositlerde geri dönüşümsüz hasar oluşturabilmektedir. Sistolik ve diastolik fonksiyon kaybına yol açabilmektedir. Kalp yetmezliğine götürmektedir 8, 9 . ADR vücuda girdiğine Results: We observed that the ADR group showed histopathological impairment compared to the Control group and that CLQ treatment improved this ADRinduced damage. In the ADR group, there was an increase in GRP78 and TNF-α immunoreactivity compared to the control group p

Keywords

Adriamycin, chloroquine, heart, endoplasmic reticulum stress, inflammation

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