COX-mediated Regulation of Multiple Organ Damage by Betulin Treatment in Okadaic Acid-induced Alzheimer Rat Model

Abstract

Objective: Alzheimer's Disease (AD) is a progressive neurodegenerative disease. Cyclooxygenases (COXs) are essential in the inflammatory and regenerative processes of AD. This study aims to show that Betulin, a natural phytochemical (triterpene), is a candidate for COX-mediated correction of multiple organ damage of AD. Materials and Methods: In this study, the effects and treatment potential of Betulin were investigated in the kidney, heart, and small intestine tissue in genetic, and histological contexts in an okadaic acid-induced rat AD model. A total of 36 Wistar albino male rats were included in the study. Cyclooxygenase 1 (COX-1) and Cyclooxygenase 2 (COX2) gene expressions were investigated by quantitative real-time PCR (qRT-PCR) in kidney, heart, and small intestine tissues. COX-1 and COX-2 proteins in tissues were analyzed by immunohistochemistry. Results: COX-1 and COX-2 genes were detected to be overexpressed in the AD model. The expression of both genes was increased in the AD model and decreased after betulin treatment. Histological scores showed a strong positive effect of Betulin on the kidney, while it was relatively less effective on the heart and small intestine tissue. Conclusion: In treating organ damage in AD, COXs can be inhibited by Betulin and may be effective in functional recovery.

Keywords

• Alzheimer’s disease
• cyclooxygenase 1
• cyclooxygenase 2
• betulin
• organ damage

Okadaik Asitle İndüklenen Alzheimer Sıçan Modelinde Betulin Tedavisi ile Çoklu Organ Hasarının COX Aracılığıyla Düzenlenmesi

Abstract

Amaç: Alzheimer Hastalığı (AH) ilerleyici bir nörodejeneratif hastalıktır. Siklooksijenazlar (COX'ler), AH 'nin inflamatuar ve rejeneratif süreçlerinde gereklidir. Bu çalışma, doğal bir fitokimyasal (triterpen) olan Betulin'in, AH 'nin çoklu organ hasarının COX aracılı düzeltilmesi için aday olduğunu göstermeyi amaçlamaktadır. Materyal ve Metod: Bu çalışmada okadaik asit ile indüklenen sıçan AH modelinde betulin'in böbrek, kalp ve ince bağırsak dokusundaki genetik ve histolojik bağlamdaki etkilerini ve tedavi potansiyeli araştırılmıştır. Çalışmaya 36 adet Wistar albino erkek sıçan dahil edildi. Böbrek, kalp ve ince bağırsak dokularında Cyclooxygenase 1 (COX1) ve Cyclooxygenase 2 (COX2) gen ekspresyonları kantitatif gerçek zamanlı PCR (qRT-PCR) ile araştırılmıştır. Dokulardaki COX-1 ve COX2 proteinleri immünohistokimya ile analiz edildi. Bulgular: AH modelinde COX1 ve COX2 genlerinin aşırı eksprese edildiği tespit edildi. Her iki genin ekspresyonu AH modelinde artmış ve betulin tedavisinden sonra azalmıştır. Histolojik skorlar Betulin'in böbrek üzerinde güçlü bir olumlu etkisi olduğunu, kalp ve ince bağırsak dokusu üzerinde ise nispeten daha az etkili olduğunu gösterdi. Sonuç: AH'de organ hasarının tedavisinde COX'lar betulin tarafından inhibe edilebilir ve fonksiyonel iyileşmede etkili olabilir.

Keywords

• Alzheimer hastalığı
• cyclooxygenase 1
• cyclooxygenase 2
• betulin
• organ hasarı

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