Sıçanlarda doksorubisine bağlı kardiyotoksisite üzerine vinkristin ve zeytin yaprağı ekstratının (tyrosol) serum biyokimyasal ve histopatolojik etkilerinin karşılaştırılması
Date
2023-07-25
Authors
Ateş, Özge
Journal Title
Journal ISSN
Volume Title
Publisher
Bursa Uludağ Üniversitesi
Abstract
Gerçekleştirdiğimiz çalışmada sıçanlarda doksorubisine bağlı kardiyotoksisite üzerine vinkristin ve zeytin yaprağı ekstratının (tyrosol) sıçanlara ait serum biyokimyasal, histopatolojik parametreler üzerindeki etkilerinin araştırılması amaçlandı. Çalışmada 49 adet Sprague Dawley sıçanı kullanıldı. Sıçanlar kontrol (K), doksorubisin (D), vinkristin (V), tyrosol (zeytin yaprağı ekstratı) (T), doksorubisin+vinkristin (D+V), doksorubisin+tyrosol (zeytin yaprağı ekstratı)(D+T), doksorubisin+vinkristin+tyrosol (zeytin yaprağı ekstratı)(D+V+T) grupları olmak üzere her çalışma grubunda 7 denek olacak şekilde rastgele 7 grup oluşturuldu. Tüm sıçanlara gün aşırı 6 doz olmak üzere intraperitoneal ilaç uygulaması yapıldı. Çalışmanın son gününde, sıçanlar derin anesteziye alındı. İntrakardiyak olarak kalpten serum biyokimyasal incelemeler için kan numuneleri toplandı. Histopatolojik incelemeler için kalp, karaciğer ve akciğerden, gen analizi için kalpten dokular toplandı. İlaç uygulamaları süresince sadece D+V+T grubunda 2 adet sıçanda ölüm gözlenmiştir. Deneysel süreçte sıçanların haftalık ağırlık ölçümleri yapıldı. Ağırlık ölçümlerinde doksorubisin uygulanan sıçan gruplarında vücut ağırlıklarında azalma olduğu gözlendi. Biyokimyasal parametreler incelendiğinde, cTnI, ALT, LDH, CKMB verileri incelendiğinde gruplardan elde edilen sonuçlarda istatiksel olarak anlamlı farklılıklar olduğu gözlendi (P<0,05). Mikroskobik değerlendirme için alınan kalp dokularında miyokard tabakasında ödem-şişme-kanama, disorganizasyon, vakuolizasyon, nekroz ve yangı lezyonları tespit edildi veskorlandı. Histopatolojik bulgular incelendiğinde sadece yangı değerinde gruplar arasında farklılıklar olmadığı saptandı. Gruplara ait TNNT2 geninin mRNA ekspresyon düzeyindeki değişimleri incelendiğinde, kontrol grubuna göre doksorubisinin gen ekspresyonunu baskıladığı, ancak T (tyrosol) grubunun mRNA ekspresyon seviyelerini arttırdığı görüldü. Elde edilen sonuçlar değerlendirildiğinde, sıçanlarda doksorubisine bağlı kardiyotoksisite üzerine zeytin yaprağı ekstratı(tyrosol), serum biyokimyasal olarak kardiyoprotektif etki sağlamazken, histopatolojik olarak ve TNNT2 geninin mRNA ekspresyon düzeyindeki değişimleri incelendiğinde kardiyoprotektif etki sağladığı belirlenmiştir. Koruyucu etkilerin oluşması için ilaçların uygulandığı günlerde değişiklik yapılması ve deney süresinin uzatılması gibi değişikliklerle ileri çalışmalara gereksinim vardır.
In our study, it was aimed to investigate the effects of vincristine and olive leaf extract(tyrosol) on doxorubicin-induced cardiotoxicity in rats on serum biochemical and histopathological parameters of rat. 49 Sprague Dawley rats were used in the study. The rats were randomly divided into 7 groups with 7 rats in each group as control (K), doxorubicin (D), vincristine (V), tyrosol (olive leaf extract)(T), doxorubicin+vincristine (D+V), doxorubicin+ tyrosol (olive leaf extract) (D+T), doxorubicin+vincristine+ tyrosol (olive leaf extract) (D+V+T) groups. Intraperitoneal drug administration was applied to all groups as 6 doses every two day. On the last day of the study, the rats were placed under deep anesthesia. Intracardiac blood samples were collected from the heart for serum biochemical examinations. Tissues were collected from the heart, liver and lungs for histopathological examinations, and from the heart for gene analysis. During drug administration, death was observed only in 2 rats in D+V+T group. During the experimental process, weekly weight measurements of the rats were made. In weight measurements, it was observed that there was a decrease in body weight in the rat groups administered doxorubicin. When biochemical parameters were examined, cTnI, ALT, LDH, CKMB data were analyzed, it was observed that there were statistically significant differences between the groups (P<0,05). Edema-swelling-bleeding, disorganization, vacuolization, necrosis and inflammatory lesions in the myocardial layer were detected and scored in the heart tissues taken for microscopic evaluation. When the histopathological findings were examined, it was determined that there were no differences between the groups only in the inflammatory lesion. When the changes in the mRNA expression level of the TNNT2 gene belonging to the groups were examined, it was found that doxorubicin suppressed gene expression compared to the control group, but increased the mRNA expression levels of the T (tyrosol) group. When the results obtained were evaluated, it was determined that olive leaf extract (tyrosol) did not provide a cardioprotective effect in serum biochemically on doxorubicin-induced cardiotoxicity in rats, but when the changes in the mRNA expression level of the TNNT2 gene were examined and histopathologically, it was found to provide a cardioprotective effect. In order for protective effects to occur, further studies are needed with changes such as making changes to the days when medications are administered and extending the experimental period.
In our study, it was aimed to investigate the effects of vincristine and olive leaf extract(tyrosol) on doxorubicin-induced cardiotoxicity in rats on serum biochemical and histopathological parameters of rat. 49 Sprague Dawley rats were used in the study. The rats were randomly divided into 7 groups with 7 rats in each group as control (K), doxorubicin (D), vincristine (V), tyrosol (olive leaf extract)(T), doxorubicin+vincristine (D+V), doxorubicin+ tyrosol (olive leaf extract) (D+T), doxorubicin+vincristine+ tyrosol (olive leaf extract) (D+V+T) groups. Intraperitoneal drug administration was applied to all groups as 6 doses every two day. On the last day of the study, the rats were placed under deep anesthesia. Intracardiac blood samples were collected from the heart for serum biochemical examinations. Tissues were collected from the heart, liver and lungs for histopathological examinations, and from the heart for gene analysis. During drug administration, death was observed only in 2 rats in D+V+T group. During the experimental process, weekly weight measurements of the rats were made. In weight measurements, it was observed that there was a decrease in body weight in the rat groups administered doxorubicin. When biochemical parameters were examined, cTnI, ALT, LDH, CKMB data were analyzed, it was observed that there were statistically significant differences between the groups (P<0,05). Edema-swelling-bleeding, disorganization, vacuolization, necrosis and inflammatory lesions in the myocardial layer were detected and scored in the heart tissues taken for microscopic evaluation. When the histopathological findings were examined, it was determined that there were no differences between the groups only in the inflammatory lesion. When the changes in the mRNA expression level of the TNNT2 gene belonging to the groups were examined, it was found that doxorubicin suppressed gene expression compared to the control group, but increased the mRNA expression levels of the T (tyrosol) group. When the results obtained were evaluated, it was determined that olive leaf extract (tyrosol) did not provide a cardioprotective effect in serum biochemically on doxorubicin-induced cardiotoxicity in rats, but when the changes in the mRNA expression level of the TNNT2 gene were examined and histopathologically, it was found to provide a cardioprotective effect. In order for protective effects to occur, further studies are needed with changes such as making changes to the days when medications are administered and extending the experimental period.
Description
Keywords
Doksorubisin, Vinkristin, Tyrosol, Sıçan, Kardiyotoksisite, Doxorubicin, Vincristine, Rat, Cardiotoxicity
Citation
Ateş, Ö. (2023). Sıçanlarda doksorubisine bağlı kardiyotoksisite üzerine vinkristin ve zeytin yaprağı ekstratının (tyrosol) serum biyokimyasal ve histopatolojik etkilerinin karşılaştırılması. Yayınlanmamış doktora tezi. Bursa Uludağ Üniversitesi Sağlık Bilimleri Enstitüsü.