Kemoterapi Kaynaklı Hepatotoksisiteye Karşı Ellajik Asitin Koruyucu Etkileri

Abstract

Amaç: Siklofosfamid (CP), hepatotoksisite dahil olmak üzere, toksik yan etkilerine rağmen yaygın olarak kullanılan kemoterapötik bir ajandır. Ellajik asit (EA) antioksidan bir ajandır ve serbest radikal süpürücü aktiviteler sergilemektedir. Bu deneysel çalışmada, EA'nın, CP'ye bağlı karaciğer hasarı üzerindeki etkileri araştırılmıştır.

Gereç ve Yöntemler: Yirmi dört adet Sprague-Dawley türü sıçan (180-220 gr) dört eşit gruba ayrıldı. Hepatotoksisite oluşturmak için intraperitonal olarak tek doz 150 mg/kg CP verildi. CP uygulamasından 20 dakika önce ve 4 ila 8 saat sonra oral yolla farklı dozlarda (50 ve 75 mg/kg) EA uygulandı. Serumun biyokimyasal analizlerinin yanı sıra böbrek dokularının histopatolojik değerlendirmesi ve kaspaz-3 için immünohistokimyasal değerlendirme yapıldı.

Bulgular: CP uygulanan grup, kontrol grubuna kıyasla, serum hepatik enzimleri olan aspartat aminotransferaz (AST) ve alanin aminotransferaz (ALT)’da önemli bir artış gösterdi. Benzer şekilde, total trigliserit (TG) ve çok düşük yoğunluklu lipoprotein kolesterol (VLDL-C) seviyeleri önemli ölçüde arttı. Ayrıca, yüksek yoğunluklu lipoprotein kolesterol (HDL-C) seviyeleri, kontrol grubuna kıyasla anlamsız olarak azaldı. Her iki EA dozunda da VLDL-C, AST, ALT seviyeleri önemli ölçüde azalırken, HDL-C seviyesi önemli bir artış gösterdi. 75 mg/kg EA tedavisi, total kolesterol (TC) konsantrasyonunda önemsiz bir artışa neden oldu. CP uygulanan grubun karaciğerlerinde mikroskobik olarak önemli derecede konjesyon, ödem, dejenerasyon ve nekroz gözlendi. Bununla beraber EA-75 grubundaki hayvanlarda ödem, dejenerasyon ve nekroz önemli ölçüde azaldı. Ayrıca kaspaz-3 ekspresyonu EA-75 grubunda anlamlı şekilde azaldı.

Sonuç: Bu sonuçlar sıçanlarda CP'nin neden olduğu hepatotoksisitede EA'nın koruyucu etkisi olduğunu göstermiştir.

Keywords

• kaspaz-3
• siklofosfamid
• ellajik asit
• hepatotoksisite
• lipidler

Protective Effects of Ellagic Acid Against Chemotherapy-Induced Hepatotoxicity

Abstract

Aim: Cyclophosphamide (CP) is a commonly used chemotherapeutic agent despite its toxic adverse effects, including hepatotoxicity. Ellagic acid (EA) is an antioxidant agent and exhibits free radical scavenging activities. In this experimental study, the effects of EA on CP-induced liver injury were investigated.

Material and Methods: Twenty-four Sprague-Dawley rats (180-220 gr) were separated into four equal groups. A single dose of 150 mg/kg CP was given intraperitoneally to generate hepatotoxicity. Different doses (50 and 75 mg/kg) of EA were administered orally 20 minutes before, 4 and 8 hours after CP administration. The histopathological evaluation of kidney tissues and immunohistochemical evaluation for caspase-3 were conducted as well as the serum biochemical analyses.

Results: CP treated group exhibited a significant increase in serum hepatic enzymes, aspartate aminotransferase (AST) and alanine aminotransferase (ALT), compared to the control group. Similarly, the total triglycerides (TG) and very-low-density lipoprotein cholesterol (VLDL-C) levels increased significantly. Additionally, the high-density lipoprotein cholesterol (HDL-C) levels decreased, which was not significant, compared to the control group. At both EA doses, VLDL-C, AST, ALT levels decreased significantly while HDL-C level revealed a significant increase. 75 mg/kg EA treatment caused a non-significant elevation in total cholesterol (TC) concentration. Microscopic analysis showed a significant congestion, edema, degeneration and necrosis in the livers of CP administered group. However, edema, degeneration, and necrosis were significantly reduced in animals treated with EA-75. In addition, caspase-3 expression significantly decreased in EA-75 group.

Conclusion: These results indicate the protective effects of EA in CP-induced hepatotoxicity in rats.

Keywords

• caspase-3
• cyclophosphamide
• ellagic acid
• hepatotoxicity
• lipids

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