The role of oxidative stress, apoptosis and altered TRPM2 channel activation in doxorubicin-induced liver injury; the protective effect of selenium

Year 2024, Volume: 8 Issue: 2, 118 - 124, 30.08.2024

Kenan Yıldızhan , Zübeyir Huyut , Fikret Altındağ , Mehmet Hafit Bayir

https://doi.org/10.30565/medalanya.1483307

Abstract

Aim: Doxorubicin (DOXR) is frequently used alone or as combination therapy in the treatment of various types of cancer. Although dose-dependent side effects are known, its effects on liver health are not fully known. This study aimed to investigate the role of the transient receptor potential melastatin-2 (TRPM2) channel in DOXR-treated rats using the TRPM-2 channel blocker N-(p-amylcinamoyl) anthranilic acid (ACA) and to investigate the protective effects of selenium (Se).

Methods: Rats were allocated into six groups, each containing ten rats: control, DMSO, DOXR, DOXR + Se, DOXR + ACA, and DOXR + ACA + Se. Serum levels of AST, ALT, LDH, triglycerides, and total cholesterol were measured. Additionally, liver tissues were subjected to immunohistochemical tests for TRPM2 channel, 8-OHdG, and caspase-3 (Casp-3) expressions and also histopathological evaluation.

Results: Serum AST, ALT, LDH, triglyceride and total cholesterol levels, as well as liver 8-OHdG, TRPM2 channel and Casp-3 expressions in the DOXR group were significantly higher than in the DOXR + Se, DOXR + ACA and DOXR + ACA + Se groups (p < 0.05). However, these parameters were significantly reduced in the Se and ACA-treated groups compared to the DOXR group (p < 0.05).

Conclusions: The results suggest that simultaneous administration of Se or ACA with DOXR may provide an effective therapeutic approach to combat DOXR-induced hepatotoxicity.

Keywords

Apoptosis, Doxorubicin, Hepatotoxicity, Lipid Profile, TRPM2 Channel

Doksorubisin kaynaklı karaciğer hasarında oksidatif stres, apoptoz ve değişen TRPM2 kanalı aktivasyonunun rolü; selenyumun koruyucu etkisi

Abstract

Amaç: Doksorubisin (DOXR) çeşitli kanser türlerinin tedavisinde sıklıkla tek başına veya kombinasyon terapisi olarak kullanılmaktadır.doza bağlı olarak değişen yan etkiler bilinmesine rağmen, karaciğer sağlığı üzerindeki etkileri tam olarak bilinmemektedir. Bu araştırma, DOXR ile tedavi edilen sıçanlarda geçici reseptör potansiyeli melastatin-2 (TRPM2) kanalının rolünü, TRPM-2 kanal blokörü N-(p-amilsinamoil) antranilik asit (ACA) kullanarak araştırmayı ve selenyum (Se)'un koruycu etkilerini araştırmayı amaçladı.

Yöntemler: Sıçanlar altı gruba ayrıldı (n=10): kontrol, DMSO, DOXR, DOXR + Se, DOXR + ACA ve DOXR + ACA + Se. Serum AST, ALT, LDH, trigliserit ve total kolesterol seviyeleri ölçüldü. Ayrıca, karaciğer dokusunda TRPM2 kanalı, 8-OHdG ve kaspaz-3 (Casp-3) ekspresyonları için immünohistokimyasal testler ve ayrıca histopatolojik değerlendirme yapıldı.

Bulgular: Serum AST, ALT, LDH, trigliserid ve total kolesterol seviyeleri ve ayrıca karaciğer 8-OHdG, TRPM2 kanalı ve Casp-3 ekspresyonları DOXR grubunda DOXR + Se, DOXR + ACA ve DOXR + ACA + Se gruplarına göre anlamlı derecede yüksekti (p <0.05). Ancak, bu parametreler Se ve ACA ile tedavi edilen gruplarda DOXR grubuna kıyasla önemli ölçüde düşmüştü (p <0.05).

Sonuç: Sonuçlar, Se veya ACA'nın DOXR ile eşzamanlı uygulanmasının, DOXR kaynaklı hepatotoksisiteyle mücadelede etkili bir terapötik yaklaşım sağlayabileceğini göstermektedir.

Keywords

Apoptoz, Doksorubisin, Hepatotoksisite, Lipid Profili, TRPM2 Kanalı

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