Akut Akciğer Hasarı Modelinde Hispidulinin Hepatoprotektif Rolünün Karaciğer Biyomoleküler Kompozisyonu Değişimleri Açısından Değerlendirilmesi

Abstract

Akut solunum sıkıntısı sendromu (ARDS), ciddi hipoksemi, pulmoner ödem, pulmoner hücresel infiltrasyon ve yaygın alveoler hasar ile karakterize edilen ani solunum yetmezliğinin bir çeşit semptom kompleksidir. ARDS olan kritik hastalar, karaciğer fonksiyonunun bozulması açısından yüksek risk altındadır çünkü karaciğer, mediatörleri düzenleyen ve enflamatuar bozukluklar sırasında organ etkileşimlerini modüle eden önemli bir organdır. Bu nedenle ARDSli hastalarda karaciğeri koruyacak hepatoprotektif özellikte yeni ajanların belirlenmesine ihtiyaç vardır. Bu çalışmada, oleik asit kaynaklı akut akciğer hasarı sıçan modelinde Hispidulin'in potansiyel hepaprotektif aktivitesi, Fourier Dönüşümlü Kızılötesi Spektroskopisi ve denetimsiz örüntü tanıma yöntemleri kullanılarak biyokimyasal kompozisyon değişiklikleri açısından belirlenmiştir. Çalışmada erkek Sprague Dawley cinsi sıçanlardan I. Kontrol, II. ARDS, III. ARDS + Hispidulin olmak üzere 3 grup oluşturulmuştur. Kontrol grubu hariç diğer iki gruba 50μL Oleik asit intravenöz olarak verilmiştir. Grup III'teki hayvanlara Oleik asit enjeksiyonlarından bir saat önce 80 mg/kg intraperitoneal Hispidulin uygulanmıştır. Gruplar arasındaki bağıntıları ve biyomoleküler değişimleri belirlemek için elde edilen spektrumlara temel bileşen analizi (TBA) ve hiyerarşik kümele analizi (HCA) uygulandı. PCA skor ve HCA dendrogram grafiklerine göre, ARDS grubu %100 doğruluk, özgüllük ve duyarlılık değeri ile diğer iki gruptan ayrı bir yerde konumlanmıştır. PCA analizinde elde edilen yükleme grafikleri özellikle ARDS kaynaklı karaciğer protein, lipit, kollajen ve nükleit asit içeriğinde değişimlerin olduğunu, hispidulin önuygulamasının bu değişimlerin oluşmasını engellediğini, akut akciğer hasarında hepatoprotektif potansiyeli olduğunu göstermektedir.

Keywords

• ATR-FTIR spektroskopisi
• Hispidulin
• ARDS
• Temel bileşen analizi
• Hiyerarşik kümeleme analizi
• Biyomoleküler kompozisyon

Evaluation of Hepatoprotective Role of Hispidulin in Terms of Liver Biomolecular Composition Changes in Acute Lung Injury Model

Abstract

Acute respiratory distress syndrome (ARDS) is a symptom complex of sudden respiratory failure characterized by severe hypoxemia, pulmonary edema, pulmonary cellular infiltration, and diffuse alveolar damage. Critically ill patients with ARDS are at high risk for impaired liver function because the liver is a vital organ that regulates mediators and modulates organ interactions during inflammatory disorders. Therefore, there is a need to identify new hepatoprotective agents to protect the liver in patients with ARDS. In the present study, the potential hepaprotective activity of Hispidulin in the oleic acid-induced ARDS rat model was determined regarding biochemical composition changes using Fourier Transform Infrared Spectroscopy and unsupervised pattern recognition methods. In this study, three groups of male Sprague Dawley rats were formed as I. Control, II. ARDS, III. ARDS + Hispidulin. Except for the control group, the other two groups received 50μL Oleic acid intravenously. Group III animals were administered Hispidulin 80 mg/kg intraperitoneally one hour before Oleic acid injections. Principal component analysis (PCA) and hierarchical cluster analysis (HCA) were applied to IR spectra to determine the relationships and biomolecular changes between the groups. According to the PCA score and HCA dendrogram graphs, the ARDS group was well discriminated from the other two groups with 100% accuracy, sensitivity and specificity. The PCA loading plot showed the changes in liver protein, lipid, collagen, and nucleic acid contents, mainly due to ARDS; hispidulin preadministration prevented these changes, indicating the hepatoprotective potential of hispidulin in acute lung injury.

Keywords

• ATR-FTIR spectroscopy
• Hispidulin
• ARDS
• Principal component analysis
• Hierarchical cluster analysis
• Biomolecular composition

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