Investigation of DNA damage and inflammatory marker profile in patients after bariatric surgery

Öz

Purpose: Obesity is a significant risk factor in the development of many serious diseases. The most prominent ones among them are diabetes and coronary heart disease. Elevated blood sugar levels in obese individuals lead to increased susceptibility to infections due to the suppression of the immune response. Moreover, fatty skin folds can cause topical infections, ulcers, and delayed/impaired wound healing. Therefore, inflammatory and pro-inflammatory markers in the serum have gained importance in diseases such as diabetes and obesity. Furthermore, in obesity, reactive oxygen species (ROS) lead to DNA damage. 8-oxo-dG, which is the primary product of DNA oxidation, can be detected in the serum, saliva, and urine, making it an ideal biological marker for DNA damage in large population-based studies. The Comet assay analysis is a method used to demonstrate the double-strand breaks in DNA. Induction of γ-H2AX in tissue indicates the initiation of a well-regulated mechanism to reverse double-strand breaks in DNA. Potential benefits of monitoring the genomic health in obesity include creating a sense of urgency for personalized intervention measures and evaluating their progress. DNA damage in obesity is believed to be a reversible condition. Chronic inflammation is an etiological factor known to support DNA damage and neoplastic transformations in cells. Cytokines secreted from adipose tissue, especially TNF-alpha, IL-6, and IL-1β, promote the accumulation of various cells, including neutrophils, macrophages, and dendritic cells, and it indicates the initiation of an inflammatory process. In this project, it was aimed to investigate possible changes in inflammation markers and DNA damage in individuals undergoing bariatric surgery, who were beginning to improve endocrine and metabolic syndrome markers. Materials and methods: For this purpose, blood and urine samples were collected from 45 obese patients, who had undergone bariatric surgery and 45 healthy volunteers matched for age and gender. The levels of inflammatory markers (IL-1β, IL-6, IL-8, and TNF-α) and the DNA damage marker γ-H2AX in serum, as well as the amount of 8-oxo-dG in urine, were determined using ELISA. Additionally, the percentage of DNA damage was determined using the Comet assay analysis. Results: Weight control achieved through bariatric surgery and the subsequent reduction in fat tissue resulted in a significant decrease in the levels of γ-H2AX and 8-oxo-dG, as well as a parallel significant reduction in the percentage of DNA damage in the Comet assay results. The significant decrease in inflammatory markers IL-1β, IL-6, IL-8, and TNF-α levels indicated that bariatric surgery also affects inflammation indirectly. Conclusion: Although there are numerous studies in the literature on individual parameters related to DNA damage in various diseases and obesity, it is believed that the present study determining DNA damage, oxidation, and repair mechanisms simultaneously with inflammatory marker levels serves as a guiding example for comparing genomic health and stability in pre-obese, post-obese, and non-obese individuals.

Anahtar Kelimeler

• Obesity
• DNA damage
• inflammation
• bariatric surgery

Obezite ameliyatı sonrası hastaların DNA hasarı ve inflamatuar marker profilinin araştırılması

Öz

Amaç: Obezite, birçok ciddi hastalığın gelişmesinde önemli bir risk faktörüdür. Bunlar arasında en büyük payı diyabet ve koroner kalp hastalıkları oluşturmaktadır. Yüksek kan şekeri immün yanıtı baskıladığından obezlerde enfeksiyona yatkınlık artmaktadır. Ayrıca yağlı deri katlantıları topikal enfeksiyon, ülser ve gecikmiş-bozulmuş yara iyileşmesi sorunlarına neden olmaktadır. Bu nedenle diyabet ve obezite gibi hastalıklarda serumdaki inflamatuar ve pro-inflamatuar markerlar önem kazanmıştır. Ayrıca obezitede reaktif oksijen türleri (ROS), DNA hasarına neden olur. DNA oksidasyonunun başlıca ürünü olan 8-oxo-dG serum, tükürük ve idrarda tespit edilebilir, bu da büyük popülasyon bazlı çalışmalar için ideal bir DNA hasarı biyolojik belirleyicisidir. Komet assay analizi DNA çift zincir kırıklarının gösterilmesi için kullanılan bir yöntemdir. Dokuda γ-H2AX indüksiyonu, DNA'nın çift iplik kırıklarının tersine çevrilmesi için iyi düzenlenmiş bir mekanizmanın başladığını göstermektedir. Obezitede genom sağlığını izlemenin potansiyel faydaları, kişiselleştirilmiş müdahale önlemlerinin aciliyetini oluşturmak ve ilerlemelerini değerlendirmek için önemlidir. Obezitedeki DNA hasarının, geri dönüşümlü bir durum olduğu düşünülmektedir. Kronik inflamasyon, DNA hasarı ve hücrelerde neoplastik dönüşümlerin destekleyicisi olarak bilinen bir etiyolojik faktördür. Adipoz dokudan salgılanan sitokinler, özellikle TNF-alfa, IL-6 ve IL-1β, nötrofiller, makrofajlar ve dendritik hücreler dahil olmak üzere çeşitli hücrelerin toplanmasını teşvik eder ve bu da inflamatuar bir sürecin başladığını göstermektedir. Biz bu proje ile obezite operasyonu ile endokrin ve metabolik sendrom belirteçleri düzelmeye başlayan bireylerde inflamasyon markerları ve DNA hasarı üzerine olası değişimlerini araştırmayı amaçladık. Gereç ve yöntem: Bu amaçla 45 adet obezite ameliyatı geçirmiş hasta ve bu hastalarla yaş ve cinsiyet açısından uyumlu olan 45 adet sağlıklı gönüllüden kan ve idrar örnekleri alınmıştır. İnflamatuar marker IL-1β, IL-6, IL-8 ve TNF-α ve DNA hasar markerı γ-H2AX’in serum miktarı ve ayrıca idrarda 8-oxo-dG miktarı ELISA ile tespit edilmiştir. Komet assay analizi ile de DNA hasar yüzdesi tespit edilmiştir. Bulgular: Obezite ameliyatı ile sağlanan kilo kontrolü ve dolayısı ile yağ dokusundaki azalma, DNA hasarı üzerinde γ-H2AX ve 8-oxo-dG miktarının azalması ve buna paralel olarak komet assay sonuçlarında da DNA hasar yüzdesinin anlamlı derecede azalması ile sonuçlanmıştır. İnflamasyon markerları IL-1β, IL-6, IL-8 ve TNF-α miktarlarının anlamlı derecede azalması obezite ameliyatının dolaylı olarak inflamasyon üzerine de etkili olduğunu göstermiştir. Sonuç: Literatürde DNA hasarına ilişkin tekil parametrelerle ilgili birçok hastalıkta ve obezitede çalışma bulunmakla birlikte, DNA hasarının, oksidasyonunun ve tamir mekanizmasının belirlenmesi ve inflamasyon markerlarının da eş zamanlı seviyelerinin belirlenmesi sayesinde genom sağlığı ve stabilitesinin obezite öncesi, sonrası ve non-obez bireylerde karşılaştırılması açısından çalışmamızın yol gösterici olduğunu düşünmekteyiz.

Anahtar Kelimeler

• Obezite
• DNA hasarı
• inflamasyon
• obezite ameliyatı

Kaynakça

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