Evaluation of the Efficacy of Quercetin Against DNA, Lipid, and Protein Damage in a Diabetic Rat Model

Abstract

Diabetes Mellitus (DM) induces oxidative stress, causing severe biomolecular damage. This study investigated quercetin's protective effects against protein, DNA, and lipid oxidation in streptozotocin (STZ)-induced diabetic rats. Rats received STZ (50 mg.kg-1, i.p.) and were treated with quercetin (20, 50, or 70 mg.kg-1, daily, orally) for 21 days. Malondialdehyde (MDA), advanced oxidation protein products (AOPP), nitrotyrosine (NT), and protein carbonyl content (PCC) were measured, alongside lymphocyte Comet assays. STZ significantly elevated MDA levels compared to controls, but all quercetin treatments effectively reduced MDA concentrations (p<0.05). Conversely, while diabetes increased AOPP, NT, and PCC levels, especially 70 mg.kg-1 quercetin administration paradoxically further elevated NT and PCC levels compared to the untreated STZ group (p<0.05). AOPP levels showed a similar increasing trend at lower doses, but 70 mg.kg-1 quercetin exhibited resistance against AOPP alterations, but there are no significantly differences. Comet assays revealed STZ exacerbated DNA damage, whereas 70 mg.kg-1 quercetin significantly mitigated this damage (p<0.05). In conclusion, while 70 mg.kg-1 quercetin strongly protects against STZ-induced lipid peroxidation and DNA damage, it fails to prevent the oxidative degradation of plasma proteins.

Keywords

• Comet Assay
• Diabetes Mellitus
• DNA Damage
• Lipid Peroxidation
• Protein Damage
• Quercetin

Supporting Institution

Scientific Research Projects Coordination Unit of Aydın Adnan Menderes University

Project Number

VTF-11011

Ethical Statement

This study was approved by the Local Ethics Committee of Aydın Adnan Menderes University Animal Experiments (Approval No: 2010/089, Date: 29.09.2010) and conducted in accordance with the Declaration of Helsinki.

Thanks

We would like to express our gratitude to Prof. Ayşegül Bildik, Prof. Pınar Alkım Ulutaş and Prof. Serap Ünübol Aypak for their endless support during the study. This study is based on the Ph.D. thesis entitled "Deneysel Diyabet Oluşturulan Ratlarda Protein ve DNA Hasarı Üzerine Quercetinin Etkisi" submitted by Ahmet BÜYÜKBEN to the Institute of Health Sciences, Aydın Adnan Menderes University in 2014, and a preliminary version of this study was presented as a poster presentation at the XXIV. Ulusal Biyokimya Kongresi, 2012.

Diyabetik Rat Modelinde Kuersetinin DNA, Lipit ve Protein Hasarına Karşı Etkinliğinin Değerlendirilmesi

Abstract

Diabetes Mellitus (DM), oksidatif stresi indükleyerek şiddetli biyomoleküler hasara neden olur. Bu çalışmada, streptozotosin (STZ) ile indüklenen diyabetik sıçanlarda kuersetinin protein, DNA ve lipit oksidasyonuna karşı koruyucu etkileri araştırılmıştır. Sıçanlara STZ (50 mg.kg-1, i.p.) uygulanmış ve 21 gün boyunca oral yolla kuersetin (20, 50 veya 70 mg.kg-1, gün) tedavisi verilmiştir. Malondialdehit (MDA), ileri oksidasyon protein ürünleri (AOPP), nitrotirozin (NT) ve protein karbonil içeriği (PCC) ölçülmüş; bununla birlikte lenfositlerde Komet analizi gerçekleştirilmiştir. STZ uygulaması, MDA düzeylerini kontrol grubuna göre anlamlı derecede artırırken, tüm kuersetin tedavileri MDA konsantrasyonlarını etkili bir şekilde düşürmüştür (p<0.05). Diğer yandan, diyabet AOPP, NT ve PCC seviyelerini artırırken; özellikle 70 mg.kg-1 kuersetin uygulaması, NT ve PCC düzeylerini tedavi edilmeyen STZ grubuna kıyasla paradoksal bir şekilde daha da yükseltmiştir (p<0.05). AOPP düzeyleri düşük dozlarda benzer bir artış eğilimi göstermiş, 70 mg.kg-1 kuersetin ise AOPP değişimlerine karşı direnç sergilemiştir; ancak istatistiksel olarak anlamlı bir fark bulunmamıştır. Komet analizleri, STZ'nin DNA hasarını şiddetlendirdiğini, 70 mg.kg-1 kuersetinin ise bu hasarı anlamlı ölçüde azalttığını ortaya koymuştur (p<0.05). Sonuç olarak, 70 mg.kg-1 kuersetin STZ kaynaklı lipit peroksidasyonu ve DNA hasarına karşı güçlü bir şekilde koruma sağlarken, plazma proteinlerinin oksidatif yıkımını önlemede yetersiz kalmıştır.

Keywords

• Diabetes Mellitus
• DNA Hasarı
• Komet Analizi
• Kuersetin
• Lipid Peroksidasyonu
• Protein Hasarı

Supporting Institution

Aydın Adnan Menderes Üniversitesi Bilimsel Araştırma Projeleri Koordinasyon Birimi.

Project Number

VTF-11011

Ethical Statement

Bu çalışma, Aydın Adnan Menderes Üniversitesi Hayvan Deneyleri Yerel Etik Kurulu tarafından onaylanmış (Onay No: 2010/089, Tarih: 29.09.2010) ve Helsinki Deklarasyonu'na uygun olarak yürütülmüştür.

Thanks

Çalışma süresince verdikleri sonsuz desteklerden dolayı Prof. Dr. Ayşegül Bildik, Prof. Dr. Pınar Alkım Ulutaş ve Prof. Dr. Serap Ünübol Aypak'a şükranlarımızı sunarız. Bu çalışma, Ahmet BÜYÜKBEN tarafından 2014 yılında Aydın Adnan Menderes Üniversitesi Sağlık Bilimleri Enstitüsü'ne sunulan "Deneysel Diyabet Oluşturulan Ratlarda Protein ve DNA Hasarı Üzerine Quercetinin Etkisi" başlıklı doktora tezine dayanmaktadır ve bu çalışmanın öncül bir versiyonu XXIV. Ulusal Biyokimya Kongresi, 2012'de poster bildirisi olarak sunulmuştur.

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