Determination of synergic antioxidant interactions of Ellagic acid and chemotherapy drug (Docetaxel and Mitoxantron) combinations

Yıl 2024, Cilt: 14 Sayı: 3, 735 - 750, 15.09.2024

Cuma Zehiroğlu , S. Beyza Ö. Sarıkaya

https://doi.org/10.17714/gumusfenbil.1430653

Öz

Chemotherapy drugs are commonly used in cancer treatment, despite their numerous negative side effects. Today, there are studies to reduce the side effects of these drugs and to increase their benefits by combining them with natural substances. Our study investigated the antioxidant and antiradical activities of Ellagic acid (EA), a natural substance, DOC and MIX, commonly used chemotherapeutics, as well as their combinations (EA+DOC, EA+MIX). For this purpose, the methods of DPPH• and ABTS•+ scavenging activity, Fe3+-Fe2+ and Cu2+-Cu1+ reduction capacity were used. After the study, the interactions were analysed with the combination index using Compusyn software. Concentrations with maximum synergy in combinations have been identified. For this purpose, firstly, the combination concentrations used in the antioxidant activity methods and the absorbance values were entered into the Compusyn programme. When DPPH• and ABTS•+ scavenging activity results were entered into the programme, more effective synergistic effect was observed for EA+DOC at lower concentrations (7:7µg/mL), (0.125:1µg/mL) respectively. For EA+MIX, no synergistic effect was observed with the application of DPPH scavenging activity results to the programme, while for ABTS•+ scavenging activity, more effective synergistic effect was observed at higher concentrations within the applied doses (0.750:6µg/ml). When Fe3+-Fe2+ and Cu2+-Cu1+ reduction results were applied to the programme; synergistic effect was observed at higher concentrations (17:17µg/mL) for both EA+DOC and EA+MIX and even strong synergistic effect was observed in many of them. The obtained results provide guidance for the use of these combinations in further studies, such as anticancer and enzyme studies.

Anahtar Kelimeler

Antioxidant, Chemotherapy, Compusyn, Drug, Synergistic

Elajik asit ve kemoterapi ilaç (Dosetaksel ve Mitoksantron) kombinasyonlarının sinerjik antioksidan etkileşimlerinin belirlenmesi

Öz

Kemoterapi ilaçları kanser tedavisinde yaygın olarak kullanılan ancak birçok negatif yan etkisi bulunan ilaçlardır. Günümüzde bu ilaçların yan etkilerini azaltmak ve doğal maddelerle birleştirerek faydalarını artırmak için çalışmalar bulunmaktadır. Çalışmamızda doğal bir madde olan Elajik asit (EA), yaygın olarak kullanılan kemoterapötikler olan DOC ve MIX ile bunların kombinasyonlarının (EA+DOC, EA+MIX) antioksidan ve antiradikal aktiviteleri araştırılmıştır. Bu amaçla DPPH• ve ABTS•+ giderme aktivitesi, Fe3+-Fe2+ ve Cu2+-Cu1+ indirgeme kapasitesi yöntemleri kullanılmıştır. Çalışma sonrasında etkileşimler CompuSyn yazılımı uygulanarak kombinasyon indeksi ile analiz edilmiştir. Kombinasyonlarda maksimum sinerjik gösteren konsantrasyonlar belirlenmiştir. Bu amaçla öncelikle antioksidan aktivite metotlarında kullanılan kombinasyon konsantrasyonları ve bulunan absorbans değerleri Compusyn programına girilmiştir. DPPH• ve ABTS•+ giderme aktivitesi sonuçları programa girildiğinde EA+DOC için sırasıyla daha düşük konsantrasyonlarda (7:7µg/mL), (0,125+1 µg/mL) daha etkin sinerjik etki gözlemlenmiştir. EA+MIX için ise DPPH giderme aktivitesi sonuçlarının programa uygulanmasıyla sinerjik etki gözlemlenmemiş, ABTS•+ giderme aktivitesi için ise uygulanan dozlar içinde daha yüksek konsantrasyonlarda daha etkin sinerjik etki gözlemlenmiştir (0.750:6 µg/ml). Fe3+-Fe2+ ve Cu2+-Cu1+ indirgeme sonuçları programa uygulandığında; hem EA+DOC hemde EA+MIX için daha yüksek konsantrasyonlarda (17:17µg/mL) sinerjik etki gözlenmiş olup hatta birçoğunda güçlü sinerjik etki gözlemlenmiştir. Elde edilen sonuçlar, bu kombinasyonların antikanser ve enzim çalışmaları gibi daha ileri çalışmalarda kullanılması için yol gösterici olmuştur.

Anahtar Kelimeler

Antioksidan, Kemoterapi, Compusyn, İlaç, Sinerjik

Kaynakça

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