Metotreksat Kaynaklı Karaciğer ve Böbrek Hasarında Chia Tohumu Yağının Otofajik ve Ferroptotik Hücre Ölümüne Karşı Koruyucu Etkisi

Öz

Chia tohumu yağı (CSO), çeşitli fenolik bileşiklerin yanı sıra esansiyel yağ asitleri içerir. Hızlı bölünen kanser hücrelerini ve bağışıklık sistemi hücrelerini hedef alan metotreksat (MTX), çeşitli tümör oluşumlarında kullanılır ancak böbrekler, karaciğer ve çeşitli organlar üzerinde istenmeyen etkilere neden olur. Çalışmamızda, öncelikle chia tohumu yağının karaciğer ve böbrek hasarında otofaji ve ferroptozis üzerindeki etkilerini araştırdık. Bu amaçla, 21 erkek Balb/c fareden oluşan 3 grup oluşturduk. KONTROL grubu, standart yem ve su dışında hiçbir şey almadı. MTX grubuna 1. günde intraperitoneal olarak tek doz 20 mg/kg metotreksat uygulandı. MTX-CSO grubuna ise 1. günde intraperitoneal olarak tek doz 20 mg/kg metotreksat ve gavaj yoluyla 4 ml/kg chia tohumu yağı uygulandı. Chia tohumu yağı tedavisi 7 gün boyunca devam ettirildi. 8. günde fareler ötenazi edildi ve karaciğer ve böbrek dokuları histopatolojik, immünohistokimyasal ve çift immünofloresan boyama yöntemleri kullanılarak analiz edildi. Sonuç olarak, MTX gruplarında gözlemlenen şiddetli histopatolojik bulgular MTX-CSO grubunda hafifletildi. İmmünohistokimyasal ve çift immünofloresan boyama sonuçları, MTX'in otofaji ve ferroptoz belirteçlerini aktive ederken, CSO'nun bunları baskılayarak koruyucu ve düzenleyici bir etki gösterdiğini ortaya koymaktadır. Araştırmamız CSO’ nun otofajik ve ferroptotik hücre ölümü üzerine etkisini inceleyen ilk özgün çalışmadır.

Anahtar Kelimeler

• Chia Tohumu Yağı
• Ferroptoz
• İmmünofloresans
• İmmünohistokimya
• Otofaji.

Protective İmpact of Chia Seed Oil on Autophagic and Ferroptotic Cell Death in Methotrexate-Induced Liver and Kidney Damage

Öz

Chia seed oil (CSO) essential fatty acids along with various phenolic compounds. Methotrexate (MTX), which targets rapidly dividing cancer cells and immune system cells, is used in various tumor formations but causes undesirable effects on the kidneys, liver, and various organs. In our study, we primarily investigated the effects of chia seed oil on autophagy and ferroptosis in liver and kidney damage. For this purpose, we formed 3 groups with 21 male Balb/c mice. The CONTROL group received nothing except standard feed and water. The MTX group received a single dose of 20 mg/kg methotrexate intraperitoneally on day 1. The MTX-CSO group received a single dose of 20 mg/kg methotrexate intraperitoneally on day 1, along with 4 ml/kg of chia seed oil administered via gavage. Chia seed oil treatment was continued for 7 days. On the 8th day, the mice were euthanized, and liver and kidney tissues were analyzed using histopathological, immunohistochemical, and double immunofluorescence staining methods. In conclusion, the severe histopathological findings observed in the MTX groups were alleviated in the MTX-CSO group. Immunohistochemical and dual immunofluorescence staining results show that while MTX activates autophagy and ferroptosis markers, CSO suppresses them, exhibiting a protective and regulatory effect. Our research is the first original study to investigate the effect of CSO on autophagic and ferroptotic cell death.

Anahtar Kelimeler

• Autophagy
• Chia Seed Oil
• Ferroptosis
• Immunofluorescence
• Immunohistochemistry

Kaynakça

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