Esculetin Attenuates Doxorubicin-Induced Kidney Damage By Reducing Heat Shock Proteins Expression Levels

Abstract

The effectiveness of Doxorobucin (DOX), a commonly used anti-cancer and immunosuppressive medication, is hindered by its potential for organ toxicity. Prolonged use of DOX is associated with severe hepatocellular toxicity. This study reveals fresh insights into the therapeutic impact of esculetin (E) on DOX-induced kidney cell damage. Esculetin demonstrates its remedial effects by modulating heat shock protein signaling pathways. In our research, we explored the impact of DOX and E on the expression of the 70 kDa HSP gene family, including Hspa1a, Hspa4, and Hspa5, which are small stress proteins in Rattus norvegicus. The study involved the assignment of five different groups (Control, DOX, E50 mg/kg, E100 mg/kg, DOX+ E50 mg/kg, and DOX+ E100 mg/kg). Subsequently, kidney tissues were collected from rats, and cDNA libraries were generated at the conclusion of the application process. The Real-Time PCR method was employed using these libraries to detect HSP70 genes. Analyses conducted on Hspa1a, Hspa4 and Hspa5 expression revealed a statistically significant increase in the DOX group compared to the control group. Additionally, the combination of DOX and esculetin demonstrates a reduction in the increase caused by DOX alone. The study suggests that esculetin could serve as a potential protective agent for shielding kidney tissue from oxidative damage and apoptosis.

Keywords

• Nephrotoxicity
• Oxidative stress
• Doxorobucin
• Esculetin

Eskuletin, Isı Şoku Proteinlerinin İfade Düzeylerini Azaltarak Doksorubisinin Neden Olduğu Böbrek Hasarını Azaltıyor

Abstract

Yaygın olarak kullanılan bir anti-kanser ve immünosupresif ilaç olan Doxorobucin'in (DOX) etkinliği, organ toksisitesi potansiyeli nedeniyle engellenmektedir. DOX'un uzun süreli kullanımı ciddi hepatoselüler toksisite ile ilişkilidir. Bu çalışma, eskuletin'in (E) DOX kaynaklı böbrek hücresi hasarı üzerindeki terapötik etkisine dair yeni bilgiler ortaya koymaktadır. Esculetin, ısı şoku protein sinyal yolaklarını modüle ederek iyileştirici etkilerini göstermektedir. Araştırmamızda, DOX ve E'nin Rattus norvegicus'ta küçük stres proteinleri olan Hspa1a, Hspa4 ve Hspa5 dahil olmak üzere 70 kDa HSP gen ailesinin ekspresyonu üzerindeki etkisini araştırdık. Çalışmada beş farklı grup (Kontrol, DOX, E50 mg/kg, E100 mg/kg, DOX+ E50 mg/kg ve DOX+ E100 mg/kg) oluşturulmuştur. Daha sonra sıçanlardan böbrek dokuları toplanmış ve uygulama sürecinin sonunda cDNA kütüphaneleri oluşturulmuştur. HSP70 genlerini tespit etmek için bu kütüphaneler kullanılarak Gerçek Zamanlı PCR yöntemi kullanılmıştır. Hspa1a, Hspa4 ve Hspa5 ekspresyonu üzerinde yapılan analizler, DOX grubunda kontrol grubuna kıyasla istatistiksel olarak anlamlı bir artış olduğunu ortaya koymuştur. Ek olarak, DOX ve eskuletin kombinasyonu, tek başına DOX'un neden olduğu artışta bir azalma olduğunu göstermektedir. Çalışma, eskuletin'in böbrek dokusunu oksidatif hasar ve apoptozdan korumak için potansiyel bir koruyucu ajan olarak hizmet edebileceğini göstermektedir.

Keywords

• Doksorobusin
• Eskuletin
• Nefrotoksisite
• Oksidatif stres

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