Ökse Otu (Viscum album L.) Ekstraktının Karaciğer Dokusunda İyonize Radyasyon Maruziyetinde Radyoprotektif Etkilerinin İncelenmesi
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Dosyalar
Tarih
2022
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Selçuk Üniversitesi Sağlık Bilimleri Enstitüsü
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
İyonize radyasyon (İR)’un iyonizasyon ile doğrudan, serbest radikaller aracılığıyla ise dolaylı
olarak hem kanserli hücrelerde hem de komşu normal hücrelerde hasara sebep olduğu bilinmektedir.
Bu hasarı önlemeye veya azaltmaya yönelik olarak, çalışmamızda badem ağaçları üzerinden toplanan
ökse otlarından elde edilen ekstraktın tek başına veya N-asetilsistein (NAS) ile kombine edilerek
kullanıldığında radyoterapi (RT) alan kanser hastalarında oluşabilecek oksidatif hasarın azaltılması
başta olmak üzere, yan etkilerin önlenmesinde veya azaltılmasında takviye edici bir bitkisel ürün
olarak kullanılıp kullanılamayacağını deneysel hayvan modeli ile ortaya koymayı amaçladık.
Bu kapsamda Nisan-Haziran 2019 döneminde şehir merkezi dışındaki Konya ili ve çevre
ilçelerinde yayılış gösteren doğal ağaç toplulukları arasındaki ahlat, söğüt, badem ağaçları üzerinden
toplanan ökse otları kullanılarak elde edilen etanolik ekstraktların ilk aşamada toplam fenolik madde
(TFM), toplam antioksidan kapasite (TAK) ve antioksidan aktivite (AA) analizleri yapılmıştır. Bu
analiz sonuçlarına göre öne çıkan ökse otu (VA) türü olarak belirlenen badem ökse otu (500 mg/kg,
i.g.), RT uygulanan deney gruplarında tek başına veya NAS (275 mg/kg/48 saat, i.p.) ile kombine
edilerek 14 gün süreyle uygulanmıştır. Uygulama sonunda kan ve karaciğer doku örnekleri
toplanmıştır. Serum ve doku örneklerinde biyokimyasal analizler, histopatolojik değerlendirmeler ve
immünohistokimyasal çalışmalar yapılmıştır.
Çalışma grupları arasında serum örneklerinde, total oksidan kapasite (TOK) düzeyleri
bakımından anlamlı bir farklılık (p=0,046) tespit edilmiştir. Diğer parametreler; alanin
aminotransferaz (ALT), aspartat aminotransferaz (AST), total antioksidan kapasite (TAK), oksidatif
stres indeks (OSİ)’leri ve sitokeratin-18 (M-30) bakımından ise çalışma grupları arasında anlamlı bir
fark (sırasıyla p=0,705; p=0,235; p=0,066; p=0,087; p=0,165) bulunamamıştır. Kontrol grubuna
kıyasla RT uygulanan gruplarda, 8-hidroksi-2-deoksiguanozin (8-OHdG) düzeylerinin azaldığı tespit
edilmiştir (p=0,001). Diğer parametreler (TAK, TOK, OSİ, Bax ve Bcl-2) açısından ise çalışma
grupları arasında anlamlı bir farklılık (sırasıyla p=0,105; p=0,298; p=0,111; p=0,069; p=0,469;
p=0,186) bulunamamıştır. Çalışma grupları arasında karaciğer doku örneklerinde kaspaz-3 ile
boyanan apopitotik hücre sayıları, Dapi ile işaretlenen canlı hücre sayıları ve apopitotik hücre indeks
(APİ)’leri bakımından anlamlı bir farklılık (sırasıyla p=0,353; p=0,075; p=0,144) bulunamamıştır. RT
ile indüklenen karaciğer hasarına karşı badem ökse otu (BVA) ekstraktı uygulanan çalışma grubunda,
karaciğer doku kesitlerinde portal alanda inflamasyon, santral ven ve sinüzoidal kapillerde
genişlemeler varlığında hepatosit bütünlüğünün ve radyal mimarinin RT grubuna kıyasla daha iyi
korunduğu, sınırlarının daha net olduğu izlenmiştir. Ayrıca bu grupta, RT+NAS grubundaki kadar
yoğun olmasa da, proliferatif alanlar dikkati çekmiştir. RT+NAS gubunda ise, kesit alanına giren
portal vende ve devamındaki dağıtıcı dalında konjesyon alanları ve periportal lokalizasyonlu hafif
inflamasyon gözlenirken, belirgin reaktif hücre proliferasyonu dikkati gözlenmiştir.
Elde edilen çalışma sonuçlarımıza göre, BVA’nun radyoprotektif etkinliği
doğrulanamamıştır. Daha uzun deneysel çalışma süreleriyle planlanacak kapsamlı çalışmalarla
BVA’nun radyoprotektif etkinliğinin daha net bir şekilde ortaya konabileceği düşünülmektedir.
It is known that ionizing radiation (IR) directly causes damage to both cancerous cells and neighboring normal cells through ionization and indirectly via free radicals. In order to prevent or reduce this damage, in our study, when the extract obtained from mistletoe collected from almond trees was used alone or in combination with N-acetylcysteine (NAS), it was aimed to reduce the oxidative damage that may occur in cancer patients receiving radiotherapy (RT), to prevent or prevent side effects. We aimed to demonstrate with an experimental animal model whether it can be used as a supplemental herbal product in reducing. In this context, in the first stage, the total phenolic substance (TFM), total antioxidant capacity (TAS) and antioxidant activity (AA) analyzes of the ethanolic extracts obtained by using mistletoe collected from the pewpea, willow and almond trees among the natural tree communities spreading in the province of Konya and its surrounding districts outside the city center during the April-June 2019 period were performed. Almond mistletoe (500 mg/kg, i.g.), which was determined as the prominent mistletoe (VA) species according to the results of this analysis, alone or in combination with NAS (275 mg/kg/48 hours, i.p.) in the RT-treated experimental groups, continued for 14 days. applied for a period of time. At the end of the application, blood and liver tissue samples were collected. Biochemical analyzes, histopathological evaluations and immunohistochemical studies were performed on serum and tissue samples. There was a significant difference (p=0.046) between study groups in terms of total oxidant capacity (TOS) levels in serum samples. There was no significant difference between study groups in terms of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total antioxidant capacity (TAS), oxidative stress indices (OSI) and cytokerain-18 (M-30) (p=0.705, respectively; p=0.235; p=0.066; p=0.087; p=0.165) could not be found between other parameters. It was determined that 8- hydroxy-2-deoxyguanosine (8-OHdG) levels were decreased in RT groups compared to the control group (p=0.001). No significant difference was found between the study groups in terms of other parameters (TAS, TOS, OSI, Bax, and Bcl-2) (respectively p=0.105; p=0.298; p=0.111; p=0.069; p=0.469; p=0.186). There was no significant difference between study groups in terms of apoptotic cell counts stained with caspase-3, viable cell counts marked with Dapi, and apoptotic cell indices (API) in liver tissue samples (p=0.353; p=0.075; p=0.144, respectively). In the study group, in which almond mistletoe (AVA) extract was applied against RT-induced liver damage, hepatocyte integrity and radial architecture were better preserved and the borders were clearer in the presence of inflammation in the portal area in the liver tissue sections, enlargement of the central vein and sinusoidal capillaries, compared to the RT group. In addition, proliferative areas were noted in this group, although not as intense as in the RT+NAS group. In the RT+NAS group, congestion areas and mild inflammation with periportal localization were observed in the portal vein entering the crosssectional area and its distribution branch, while significant reactive cell proliferation was observed. According to our study results, the radioprotective efficacy of AVA could not be confirmed. It is thought that the radioprotective activity of AVA can be revealed more clearly with comprehensive studies to be planned with longer experimental study times.
It is known that ionizing radiation (IR) directly causes damage to both cancerous cells and neighboring normal cells through ionization and indirectly via free radicals. In order to prevent or reduce this damage, in our study, when the extract obtained from mistletoe collected from almond trees was used alone or in combination with N-acetylcysteine (NAS), it was aimed to reduce the oxidative damage that may occur in cancer patients receiving radiotherapy (RT), to prevent or prevent side effects. We aimed to demonstrate with an experimental animal model whether it can be used as a supplemental herbal product in reducing. In this context, in the first stage, the total phenolic substance (TFM), total antioxidant capacity (TAS) and antioxidant activity (AA) analyzes of the ethanolic extracts obtained by using mistletoe collected from the pewpea, willow and almond trees among the natural tree communities spreading in the province of Konya and its surrounding districts outside the city center during the April-June 2019 period were performed. Almond mistletoe (500 mg/kg, i.g.), which was determined as the prominent mistletoe (VA) species according to the results of this analysis, alone or in combination with NAS (275 mg/kg/48 hours, i.p.) in the RT-treated experimental groups, continued for 14 days. applied for a period of time. At the end of the application, blood and liver tissue samples were collected. Biochemical analyzes, histopathological evaluations and immunohistochemical studies were performed on serum and tissue samples. There was a significant difference (p=0.046) between study groups in terms of total oxidant capacity (TOS) levels in serum samples. There was no significant difference between study groups in terms of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total antioxidant capacity (TAS), oxidative stress indices (OSI) and cytokerain-18 (M-30) (p=0.705, respectively; p=0.235; p=0.066; p=0.087; p=0.165) could not be found between other parameters. It was determined that 8- hydroxy-2-deoxyguanosine (8-OHdG) levels were decreased in RT groups compared to the control group (p=0.001). No significant difference was found between the study groups in terms of other parameters (TAS, TOS, OSI, Bax, and Bcl-2) (respectively p=0.105; p=0.298; p=0.111; p=0.069; p=0.469; p=0.186). There was no significant difference between study groups in terms of apoptotic cell counts stained with caspase-3, viable cell counts marked with Dapi, and apoptotic cell indices (API) in liver tissue samples (p=0.353; p=0.075; p=0.144, respectively). In the study group, in which almond mistletoe (AVA) extract was applied against RT-induced liver damage, hepatocyte integrity and radial architecture were better preserved and the borders were clearer in the presence of inflammation in the portal area in the liver tissue sections, enlargement of the central vein and sinusoidal capillaries, compared to the RT group. In addition, proliferative areas were noted in this group, although not as intense as in the RT+NAS group. In the RT+NAS group, congestion areas and mild inflammation with periportal localization were observed in the portal vein entering the crosssectional area and its distribution branch, while significant reactive cell proliferation was observed. According to our study results, the radioprotective efficacy of AVA could not be confirmed. It is thought that the radioprotective activity of AVA can be revealed more clearly with comprehensive studies to be planned with longer experimental study times.
Açıklama
Anahtar Kelimeler
Apopitoz, iyonize radyasyon, karaciğer hasarı, oksidatif stres, ökse otu, Apoptosis, ionizing radiation, liver damage, mistletoe, oxidative stress
Kaynak
WoS Q Değeri
Scopus Q Değeri
Cilt
Sayı
Künye
Vatansev, H., (2022). Ökse Otu (Viscum album L.) Ekstraktının Karaciğer Dokusunda İyonize Radyasyon Maruziyetinde Radyoprotektif Etkilerinin İncelenmesi. (Doktora Tezi). Selçuk Üniversitesi, Sağlık Bilimler Enstitüsü, Konya.
