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

Yıl 2023, Cilt: 6 Sayı: 4, 394 - 400, 15.10.2023

Nihal Şimşek Özek

https://doi.org/10.34248/bsengineering.1327211

Öz

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.

Anahtar Kelimeler

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

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

Öz

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.

Anahtar Kelimeler

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

Teşekkür

Sağladığı imkânlardan dolayı DAYTAM (Doğu Anadolu Yüksek Teknoloji Araştırma ve Uygulama Merkezi)’a teşekkür ederim.

Kaynakça

• Abbas S, Simsek Ozek N, Emri S, Koksal D, Severcan M, Severcan F. 2018. Diagnosis of malignant pleural mesothelioma from pleural fluid by Fourier transform-infrared spectroscopy coupled with chemometrics. J Biomed Opt, 23(10): 105003.
• Ami D, Mereghetti P, Doglia SM. 2013. Multivariate analysis for Fourier transform infrared spectra of complex biological systems and processes. Multivariate Analysis Manag Eng Sci, 2013: 189-220.
• Anan K, Kawamura K, Suga M, Ichikado K. 2018. Clinical differences between pulmonary and extrapulmonary acute respiratory distress syndrome: a retrospective cohort study of prospectively collected data in Japan. J Thorac Dis, 10: 5796.
• Ashtarinezhad A, Shirazi FH, Vatanpour H, Mohamazadehasl B, Panahyab A, Nakhjavani M. 2014. FTIR-microspectroscopy detection of metronidazole teratogenic effects on mice fetus. Iran J Pharm Res, 13: 101.
• Aydın S, Çöl M. 2020. İtalya’daki COVID-19 salgınına genel bir bakıș, Editors: Osman Memikoğlu, Volkan Genç, Covid-19, Ankara Üniversitesi Tıp Fakültesi, Ankara, Türkiye, pp: 75.
• Bellani G, Laffey JG, Pham T. 2016. Epidemiology, patterns of care, and mortality for patients with acute respiratory distress syndrome in ıntensive care units in 50 countries. JAMA, 315: 788-800.
• Cai Y, Zou Z, Liu L, Chen S, Chen Y, Lin Z, Chen Y. 2015. Bone marrow-derived mesenchymal stem cells inhibits hepatocyte apoptosis after acute liver injury. Int J Clin Exp, 8(1): 107.
• Craig AP, Franca AS, Irudayaraj J. 2013. Pattern recognition applied to spectroscopy: Conventional methods and future directions: Pattern Recognition: Practices, Perspectives and Challenges. Vincent, Eddimburg, UK, pp: 1-46.
• Çakmak G, Togan I, Uğuz C, Severcan F. 2003. FT-IR spectroscopic analysis of rainbow trout liver exposed to nonylphenol. Appl Spectrosc, 57(7): 835-841.
• Dizaji AN, Ozek NS, Yilmaz A, Aysin F, Yilmaz M. 2021. Gold nanorod arrays enable highly sensitive bacterial detection via surface-enhanced infrared absorption (SEIRA) spectroscopy. Colloids Surf B Biointerfaces, 206: 111939.
• Dominguez-Vidal A, Pantoja-de la Rosa J, Cuadros-Rodríguez L, Ayora-Cañada MJ. 2016. Authentication of canned fish packing oils by means of Fourier transform infrared spectroscopy. Food Chem, 190: 122-127.
• Elibol B, Severcan M, JakubowskaDogru E, Dursun I, Severcan F. 2022. The structural effects of Vitamin A deficiency on biological macromolecules due to ethanol consumption and withdrawal: An FTIR study with chemometrics. J Biophotonics, 15(7): e202100377.
• Fahelelbom KM, Saleh A, Al-Tabakha MM, Ashames AA. 2022. Recent applications of quantitative analytical FTIR spectroscopy in pharmaceutical, biomedical, and clinical fields: A brief review. Rev Anal Chem, 41(1): 21-33.
• Ferrandiz ML, Bustos G, Paya M, Gunasegaran R, Alcaraz MJ. 1994. Hispidulin protection against hepatotoxicity induced by bromobenzene in mice. Life Sci, 55(8): PL145-PL150.
• Gautam R, Deobagkar‐Lele M, Majumdar S, Chandrasekar B, Victor E, Ahmed SM, Nandi D. 2016. Molecular profiling of sepsis in mice using Fourier Transform Infrared Microspectroscop. J Biophotonics, 9(1-2): 67-82.
• Gok S, Aydin OZ, Sural YS, Zorlu F, Bayol U, Severcan F. 2016. Bladder cancer diagnosis from bladder wash by Fourier transform infrared spectroscopy as a novel test for tumor recurrence. J Biophotonics, 9(9): 967-975.
• Guillot A, Tacke F. 2019. Liver macrophages: old dogmas and new insights. Hepatol Commun, 3(6): 730-743.
• Gurbanov R, Bilgin M, Severcan F. 2016. Restoring effect of selenium on the molecular content, tructure and fluidity of diabetic rat kidney brush border cell membrane. Biochim Biophys Acta Biomembr, 1858(4): 845-854.
• Gurbanov R, Gozen AG, Severcan, F. 2018. Rapid classification of heavy metal-exposed freshwater bacteria by infrared spectroscopy coupled with chemometrics using supervised method. Spectrochim Acta A Mol Biomol Spectrosc, 189: 282-290.
• Herrero R, Sánchez G, Asensio I, López E, Ferruelo A, Vaquero J. 2020. Liver–lung interactions in acute respiratory distress syndrome. Intensive Care Med Exp, 8(1): 1-13.
• Hilliard KL, Allen E, Traber KE, Yamamoto K, Stauffer NM, Wasserman GA. 2015. The lung-liver axis: a requirement for maximal innate immunity and hepatoprotection during pneumonia. Am J Respir Cell Mol Biol, 53(3): 378-390.
• Hu LL, Wang WJ, Zhu QJ, Yang L. 2020. Novel coronavirus pneumonia-related liver injury: etiological analysis and treatment strategy. Chinese J Hepatol, 28(2): 97-99.
• Jin XF, Qian J, Lu YH. 2011. The role of hepatoprotective effect of a flavonoid-rich extract of Salvia plebeia R. Br. on carbon tetrachloride-induced acute hepatic injury in mice. J Medic Plant Res, 5(9): 1558-1563.
• Kamyshnyi A, Krynytska I, Matskevych V, Marushchak M, Lushchak O. 2020. Arterial hypertension as a risk comorbidity associated with COVID-19 pathology. Int J Hypertens, 2020: 8019360.
• Kaya AG, Kaya A. 2020 Klinik yaklașım: Solunum sistemi. Editors: Osman Memikoğlu Volkan Genç, Covid-19, Ankara Üniversitesi Tıp Fakültesi, Ankara, Türkiye, pp: 75.
• Lee D, Lee JH, Kim BH, Lee S, Kim DW, Kang KS. 2022. Phytochemical combination (p-Synephrine, p-octopamine hydrochloride, and hispidulin) for improving obesity in obese mice induced by high-fat diet. Nutrients, 14(10): 2164.
• Li J, Fan JG. 2020. Characteristics and mechanism of liver injury in 2019 coronavirus disease. J Clin Transl Hepatol, 8(1): 13.
• Liu K, Zhao F, Yan J, Xia Z, Jiang D, Ma P. 2020. Hispidulin: A promising lavonoid with diverse anti-cancer properties. Life Sci, 259: 118395.
• Mehra S, Chadha P. 2020. Alterations in structure of biomolecules using ATR-FTIR and histopathological variations in brain tissue of Channa punctatus exposed to 2Naphthalene sufonate. Toxicol Res, 9(4): 530-536.
• Meyer NJ, Gattinoni L, Calfee CS. 2021. Acute respiratory distress syndrome. Lancet, 398: 622-637.
• Mihály J, Deák R, Szigyártó I.C, Bóta A, Beke-Somfai T, Varga Z. 2017. Characterization of extracellular vesicles by IR spectroscopy: fast and simple classification based on amide and CH stretching vibrations. Biochim Biophys Acta Biomembr, 1859(3): 459-466.
• Nardo AD., Schneeweiss‐Gleixner M, Bakail M, Dixon ED, Lax SF, Trauner M. 2021. Pathophysiological mechanisms of liver injury in COVID‐19. Liver Int, 41(1): 32.
• Papazian L, Aubron C, Brochard L. 2019. Formal guidelines: management of acute respiratory distress syndrome. Ann Intens Care, 9: 69.
• Pocasap P, Weerapreeyakul N, Junhom C, Phiboonchaiyanan PP, Srisayam M, Nonpunya A, Barusrux S. 2020. FTIR microspectroscopy for the assessment of mycoplasmas in HepG2 cell culture. Appl Sci, 10(11): 3766.
• Redko O, Dovgalyuk A, Dovbush A, Nebesna Z, Yakubyshyna L, Krynytska I. 2021. Liver injury associated with acute respiratory distress syndrome and the prospects of mesenchymal stromal cells therapy for liver failure. Therapy, 8(12): 14-21.
• Roggo Y, Chalus P, Maurer L, Lema-Martinez C, Edmond A, Jent N. 2007. A review of near infrared spectroscopy and chemometrics in pharmaceutical technologies. J Pharm Biomed Anal, 44(3): 683-700.
• Rui L. 2014. Energy metabolism in the liver. Compr Physiol, 4(1): 177.
• Sauzier G, van Bronswijk W, Lewis SW. 2021. Chemometrics in forensic science: approaches and applications. Analyst, 146(8): 2415-2448.
• Severcan F, Haris PI. 2012. Introduction to vibrational spectroscopy in diagnosis and screening in “Vibrational Spectroscopy in Diagnosis and Screening” Adv Biomedic Spectrosc, 6: 1-10.
• Severcan F, Toyran N, Kaptan N, Turan B. 2000. Fourier transform infrared study of the effect of diabetes on rat liver and heart tissues in the C-H region. Talanta, 53(1): 55-59.
• Siqueira LF, Lima KM. 2016. MIR-biospectroscopy coupled with chemometrics in cancer studies. Analyst, 141(16): 4833-4847.
• Türker-Kaya S, İlbay G. 2020. Analysis of rat blood plasma upon acute epileptic seizures by infrared spectroscopy with chemometrics. Vib Spectrosc, 109: 103074.
• Wang Y, Alkhalidy H, Luo J, Liu D. 2019. Antidiabetic effects of hispidulin in streptozotocin‐induced insulin deficient mice. The FASEB J, 33(S1): 834-838.
• Wu F, Li S, Zhang N, Huang W, Li X, Wang M, Han B. 2018. Hispidulin alleviates high-glucose-induced podocyte injury by regulating protective autophagy. Biomed Pharmacother, 104: 307-314.
• Yang P, Formanek P, Scaglione S, Afshar M. 2019. Risk factors and outcomes of acute respiratory distress syndrome in critically ill patients with cirrhosis. Hepatol Res., 49(3): 335-343.
• Yonar D, Severcan M, Gurbanov R, Sandal A, Yilmaz U, Emri S, Severcan F. 2022. Rapid diagnosis of malignant pleural mesothelioma and its discrimination from lung cancer and benign exudative effusions using blood serum. Biochim Biophys Acta Mol Basis Dis, 1868(10): 166473.
• Zohdi V, Whelan DR, Wood BR, Pearson JT, Bambery KR, Black M. 2015. Importance of tissue preparation methods in FTIR micro-spectroscopical analysis of biological tissues:‘traps for new users. PLoS One, 10(2): e0116491.