Vazointestinal Peptid ve Naringeninin Rotenon Kaynaklı Deneysel Parkinson Hastalığı Modeli Üzerine Etkileri

Amaç: Bu çalışmanın amacı, çeşitli bilimsel çalışmalar ile etkili oldukları gösterilmiş olan naringenin ve vazointestinal peptidin (VIP) intraperitoneal olarak uygulanmasının ratlarda anti-Parkinson aktivitesi açısından değerlendirilmesidir. Gereç ve Yöntemler: Kırk sekiz adet Wistar albino dişi rat 4 gruba ayrıldı. Kontrol grubuna herhangi bir müdahale yapılmadı, RT grubuna rotenon verilirken, RT+VIP grubuna rotenon ve VIP (25 ng/kg) ve RT+NG grubuna ise rotenone ve naringenin (10 mg/kg) verildi. Tüm tedaviler 14 gün süreyle intraperitoneal yolla uygulandı. Parkinson modelinin davranış üzerindeki etkilerini göstermek için hole and board yöntemi kullanıldı. Deneyin son günü hole and board aparatı ile motor testleri yapıldı. Çalışma tamamlandıktan sonra alınan beyin dokusu örneklerinden biyokimyasal analizler yapıldı. Bulgular: RT grubuyla karşılaştırıldığında, RT+NG (p=0,023) grubunda alfa senkronizasyon düzeyi, hem RT+VIP (p=0,039) hem de RT+NG (p=0,032) gruplarında malondialdehit (MDA) düzeyleri ve RT+VIP (p=0,042) grubunda süperoksit dismutaz (SOD) inhibisyonu anlamlı olarak azalırken, RT+VIP (p=0,042) ve RT+NG (p=0,034) gruplarında ise 8-OHdG seviyeleri anlamlı şekilde arttı. Uygulanan VIP ve naringenin tedavileri ile hem biyokimyasal ve hem de motor aktivitelerinde istatistiksel olarak anlamlı şekilde düzelme saptandı. Sonuç: Elde edilen sonuçlara göre rotenon uygulaması ile Parkinson hastalığının semptomları biyokimyasal olarak oluşturulmuştur. VIP ve naringenin tedavilerinin uygulanması deneysel olarak olumlu etkiler göstermiştir ve Parkinson hastalığı ile mücadelede yardımcı bir tedavi unsuru olarak umut verici olmuştur.

The Effects of Vasointestinal Peptide and Naringenin on Rotenone-Induced Experimental Model of Parkinson's Disease

Aim: The aim of this study was to evaluate the intraperitoneal administration of naringenin and vasointestinal peptide (VIP), which are shown effective in various scientific studies, in terms of anti-Parkinsonian activity in rats. Material and Methods: Forty-eight Wistar albino female rats were divided into 4 groups. No intervention was made in the control group, rotenone was given to the RT group, rotenone and VIP (25 ng/kg) to the RT+VIP group, and rotenone and naringenin (10 mg/kg) to the RT+NG group. All treatments were administered intraperitoneally for 14 days. The hole and board method was used to show the effects of the Parkinson's model on behavior. On the last day of the experiment, motor tests were carried out with the hole and board apparatus. After the study was completed, biochemical analyzes were performed from brain tissue samples. Results: In comparison to the RT group, while the alpha-sync level in the RT+NG (p=0.023), malondialdehyde (MDA) levels both in the RT+VIP (p=0.039) and RT+NG (p=0.032), and superoxide dismutase (SOD) inhibition in the RT+VIP (p=0.042) groups decreased significantly, the 8-OHdG levels in the RT+VIP (p=0.042) and RT+NG (p=0.034) groups increased significantly. Statistically significant improvement was found both in biochemical and motor activities with the VIP and naringenin treatments applied. Conclusion: According to the results obtained, the symptoms of Parkinson's disease were formed biochemically by rotenone application. The administration of VIP and naringenin treatments has shown positive effects experimentally and has been promising as an adjunct treatment element in the fight against Parkinson's disease.

___

  • Alves da Costa C, Checler F. Apoptosis in Parkinson’s disease: is p53 the missing link between genetic and sporadic Parkinsonism? Cell Signal. 2011;23(6):963-8.
  • Dauer W, Przedborski S. Parkinson’s disease: mechanisms and models. Neuron. 2003;39(6):889-909.
  • Blandini F, Armentero MT. Animal models of Parkinson’s disease. FEBS J. 2012;279(7):1156-66.
  • Balestrino R, Schapira AHV. Parkinson disease. Eur J Neurol. 2020;27(1):27-42.
  • Poewe W, Seppi K, Tanner CM, Halliday GM, Brundin P, Volkmann J, et al. Parkinson disease. Nat Rev Dis Primer. 2017;3:17013.
  • Cannon JR, Tapias V, Na HM, Honick AS, Drolet RE, Greenamyre JT. A highly reproducible rotenone model of Parkinson’s disease. Neurobiol Dis. 2009;34(2):279-90.
  • Betarbet R, Sherer TB, MacKenzie G, Garcia-Osuna M, Panov AV, Greenamyre JT. Chronic systemic pesticide exposure reproduces features of Parkinson’s disease. Nat Neurosci. 2000;3(12):1301-6.
  • Bové J, Perier C. Neurotoxin-based models of Parkinson’s disease. Neuroscience. 2012;211:51-76.
  • Drechsel DA, Patel M. Role of reactive oxygen species in the neurotoxicity of environmental agents implicated in Parkinson’s disease. Free Radic Biol Med. 2008;44(11):1873-86.
  • Reeve A, Simcox E, Turnbull D. Ageing and Parkinson’s disease: why is advancing age the biggest risk factor? Ageing Res Rev. 2014;14(100):19-30.
  • Hu Q, Wang G. Mitochondrial dysfunction in Parkinson’s disease. Transl Neurodegener. 2016;5:14.
  • Harmar AJ, Fahrenkrug J, Gozes I, Laburthe M, May V, Pisegna JR, et al. Pharmacology and functions of receptors for vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide: IUPHAR review 1. Br J Pharmacol. 2012;166(1):4-17.
  • Tatemoto K, Mutt V. Isolation and characterization of the intestinal peptide porcine PHI (PHI-27), a new member of the glucagon--secretin family. Proc Natl Acad Sci USA. 1981;78(11):6603-7.
  • Tunçel N, Korkmaz OT, Tekin N, Şener E, Akyüz F, Inal M. Antioxidant and anti-apoptotic activity of vasoactive intestinal peptide (VIP) against 6-hydroxy dopamine toxicity in the rat corpus striatum. J Mol Neurosci. 2012;46(1):51-7.
  • Korkmaz O, Ay H, Ulupınar E, Tunçel N. Vasoactive intestinal peptide enhances striatal plasticity and prevents dopaminergic cell loss in Parkinsonian rats. J Mol Neurosci. 2012;48(3):565-73.
  • Masmoudi-Kouki O, Gandolfo P, Castel H, Leprince J, Fournier A, Dejda A, et al. Role of PACAP and VIP in astroglial functions. Peptides. 2007;28(9):1753-60.
  • Dogrukol-Ak D, Tore F, Tuncel N. Passage of VIP/PACAP/secretin family across the blood-brain barrier: therapeutic effects. Curr Pharm Des. 2004;10(12):1325-40.
  • Kalfin R, Maulik N, Engelman RM, Cordis GA, Milenov K, Kasakov L, et al. Protective role of intracoronary vasoactive intestinal peptide in ischemic and reperfused myocardium. J Pharmacol Exp Ther. 1994;268(2):952-8.
  • Delgado M, Ganea D. Vasoactive intestinal peptide: a neuropeptide with pleiotropic immune functions. Amino Acids. 2013;45(1):25-39.
  • Salehi B, Fokou PVT, Sharifi-Rad M, Zucca P, Pezzani R, Martins N, et al. The therapeutic potential of naringenin: a review of clinical trials. Pharmaceuticals (Basel). 2019;12(1):11.
  • Wilcox LJ, Borradaile NM, Huff MW. Antiatherogenic properties of naringenin, a citrus flavonoid. Cardiovasc Drug Rev. 1999;17(2):160-78.
  • Renugadevi J, Prabu SM. Naringenin protects against cadmium-induced oxidative renal dysfunction in rats. Toxicology. 2009;256(1-2):128-34.
  • Wang Q, Yang J, Zhang X, Zhou L, Liao XL, Yang B. Practical synthesis of naringenin. J Chem Res. 2015;39(8):455-7.
  • Jayachitra J, Nalini N. Effect of naringenin (citrus flavanone) on lipid profile in ethanol-induced toxicity in rats. J Food Biochem. 2012;36(4):502-11.
  • Yelkenli İH, Ulupinar E, Korkmaz OT, Şener E, Kuş G, Filiz Z, et al. Modulation of corpus striatal neurochemistry by astrocytes and vasoactive intestinal peptide (VIP) in parkinsonian rats. J Mol Neurosci. 2016;59(2):280-9.
  • Sonia Angeline M, Sarkar A, Anand K, Ambasta RK, Kumar P. Sesamol and naringenin reverse the effect of rotenone-induced PD rat model. Neuroscience. 2013;254:379-94.
  • Sonia Angeline M, Chaterjee P, Anand K, Ambasta RK, Kumar P. Rotenone-induced parkinsonism elicits behavioral impairments and differential expression of parkin, heat shock proteins and caspases in the rat. Neuroscience. 2012;220:291-301.
  • Lapointe N, St-Hilaire M, Martinoli MG, Blanchet J, Gould P, Rouillard C, et al. Rotenone induces non-specific central nervous system and systemic toxicity. FASEB J. 2004;18(6):717-9.
  • Vauzour D, Vafeiadou K, Rodriguez-Mateos A, Rendeiro C, Spencer JP. The neuroprotective potential of flavonoids: a multiplicity of effects. Genes Nutr. 2008;3(3-4):115-26.
  • Angeloni C, Vauzour D. Natural products and neuroprotection. Int J Mol Sci. 2019;20(22):5570.
  • Datla KP, Christidou M, Widmer WW, Rooprai HK, Dexter DT. Tissue distribution and neuroprotective effects of citrus flavonoid tangeretin in a rat model of Parkinson’s disease. Neuroreport. 2001;12(17):3871-5.
  • Brenneman DE. Neuroprotection: a comparative view of vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide. Peptides. 2007;28(9):1720-6.
  • Zupan V, Hill JM, Brenneman DE, Gozes I, Fridkin M, Robberecht P, et al. Involvement of pituitary adenylate cyclase-activating polypeptide II vasoactive intestinal peptide 2 receptor in mouse neocortical astrocytogenesis. J Neurochem. 1998;70(5):2165-73.
  • Liu KC, Li JY, Xie W, Li LB, Zhang J, Du CX, et al. Activation and blockade of serotonin6 receptors in the dorsal hippocampus enhance T maze and hole-board performance in a unilateral 6-hydroxydopamine rat model of Parkinson’s disease. Brain Res. 2016;1650:184-95.
  • Wang Y, Liu J, Hui Y, Wu Z, Wang L, Wu X, et al. Dose and time-dependence of acute intermittent theta-burst stimulation on hippocampus-dependent memory in parkinsonian rats. Front Neurosci. 2023;17:1124819.
  • Saleem U, Hussain L, Shahid F, Anwar F, Chauhdary Z, Zafar A. Pharmacological potential of the standardized methanolic extract of Prunus armeniaca L. in the haloperidol-induced parkinsonism rat model. Evid Based Complement Alternat Med. 2022;2022:3697522.
  • DeMaagd G, Philip A. Parkinson’s disease and its management: part 1: disease entity, risk factors, pathophysiology, clinical presentation, and diagnosis. Pharm Ther. 2015;40(8):504-32.
Düzce Tıp Fakültesi Dergisi-Cover
  • Yayın Aralığı: Yılda 3 Sayı
  • Başlangıç: 1999
  • Yayıncı: Düzce Üniversitesi Tıp Fakültesi
Sayıdaki Diğer Makaleler

Pediatrik İmmün Trombositopeni (İTP) Vakalarının ve Kronik İTP için Risk Faktörlerinin Değerlendirilmesi - Tek Merkez Deneyimi

Selçuk ERDOĞAN, Tuba KASAP, Şahin TAKÇI, Ali GÜL, Ergün SÖNMEZGÖZ, Erhan KARAASLAN, Rüveyda GÜMÜŞER, Osman DEMİR

Primer Hiperparatiroidili Hastalarda Nodüler Guatr ve Papiller Tiroid Kanseri Birlikteliğinin Değerlendirilmesi

Mustafa ÇALIŞKAN, Hasret CENGİZ, Taner DEMİRCİ

Hidroksitirozolün Diyabetik Sıçan Karaciğerinde Prdx6 Ekspresyonu Üzerindeki Etkisi

Eda Nur ALMALI, Kayihan KARACOR, Hakan SOYLU

Endometriyal Kanserde Delta Nötrofil İndeksinin Öngörücü Potansiyeli: Tanı için Yeni Bir Biyobelirteç

Caner KOSE, Büşra KÖRPE, Vakkas KORKMAZ, Yaprak USTUN

20 Yaşında Bir Kadında Perineal Epidermoid Kist Tedavisi

Fatma Başak TANOĞLU, Caglar CETİN, Osman ŞEVKET, Gürkan KIRAN, Burcu GÜL

Trifokal Göziçi Lens İmplantasyonu Sonrasında Kappa Açısı ve Fotik Fenomenler Arasındaki İlişki

Hacı KOÇ, Faruk KAYA

Akciğer Kanseri Nedeniyle Ameliyat Edilen Yaşlı Hastalarda Sağkalım ile İnflamatuvar ve Beslenme Belirteçleri Arasındaki İlişki

Oya YILDIZ, Alper FINDIKÇIOĞLU, Dalokay KILIÇ, Sinan ISSI

Müsinöz Olmayan Akciğer Adenokarsinomlarında Caspase-3 ve GRIM-19 Ekspresyonu ile Bu Proteinlerin Klinikopatolojik Önemi

Alev OK ATILGAN, Merih TEPEOĞLU, Eda YILMAZ AKÇAY, Leyla HASANALİYEVA, Dalokay KILIÇ, Handan ÖZDEMİR

Malezya'daki Malaylar Arasında İrritabl Bağırsak Sendromu (IBS) ile ilişkili Tek Nükleotid Polimorfizmlerinin Genotip ve Alel Frekansları

Rasmaizatul Akma ROSDİ, Nurfadhlina MUSA, Zalına ZAHARI, Zahrı KHAIRI, Mulham ALFATAMA, Boon Yin KHOO

Doğal Afetler sonrası Travma Sonrası Stres Bozukluğu: Bir Gözden Geçirme

Doğancan SÖNMEZ, Cicek HOCAOGLU