Glukagon Benzeri Peptid-1 Analoğu Liraglutid’in Tavuk Embriyo Modelinde Nöral Tüp Gelişimi Üzerine Etkisi

Year 2022, , 269 - 274, 30.09.2022

Hava Açar Kaya , Mehmet Aydın Akalan , İsmail Türkmenoğlu

https://doi.org/10.30607/kvj.1103958

Abstract

Bu çalışmada tip 2 diyabet ve obezite tedavisinde kullanılan inkretin bazlı glukagon benzeri peptid-1 (GLP-1) reseptör agonistlerinden liraglutid’in tavuk embriyo modelinde nöral tüp üzerine etkilerinin incelenmesi amaçlandı. Çalışmada 100 adet 61 ± 5 gr ağırlıkta, spesifik patojen içermeyen fertil yumurta 37.5 ± 0.5°C’de ve % 60 - 68 nem ortamında 28 saat inkübe edildi. Bu süre sonunda pencereleme tekniği ile açılan yumurtalar 4 gruba (n=25) ayrılarak subblastodermik olarak uygulama yapıldı. Kontrol grubuna % 0.9 steril serum fizyolojik, deney gruplarına ise 1.5, 7.5 ve 15 µg/yumurta dozda liraglutid enjekte edildi. Enjeksiyon sonrası pencereler steril drape ile kapatılarak inkübasyona bırakıldı. 48 saat inkübasyon sonunda tüm yumurtalar açılıp Hamburger-Hamilton skalası temel alınarak değerlendirildi. Çalışmada nöral tüp açıklığı, somit sayıları, Hamburger Hamilton skalasına göre gelişim evreleri incelendiğinde kontrol grubu ile deney grupları arasındaki doza bağlı farkın istatistiksel olarak anlamlı olmadığı tespit edildi (p>0.05). Baş-kıç uzunlukları bakımından yüksek doz grubu ile diğer gruplar arasındaki farkın istatistiksel olarak anlamlı olduğu tespit edildi (P<0.05). Sonuç olarak Liraglutid’in dozları ile nöral tüp açıklığı ve somit sayıları arasında anlamlı bir ilişki saptanmazken baş-kıç ölçümleri arasında farklılıklar saptandı. Liraglutid’in embriyo gelişimi üzerine etkilerinin daha net anlaşılması için ileri araştırmalar önerilmektedir.

Keywords

tavuk embriyo modeli, inkretinler, liraglutid, nöral tüp, obezite

Supporting Institution

Bu çalışma, Afyon Kocatepe Üniversitesi Bilimsel Araştırma Projeleri Koordinasyon Birimi tarafından 20.SAĞ.BİL.33 proje numarası ile desteklenmiştir.

Project Number

20.SAĞ.BİL.33

Effect of Glukagon-Like Peptide-1 Analog Liraglutide On Neural Tube Development In Chick Embryo Model

Abstract

The aim of this study is to scan different doses of Liraglutid on the neural tube in a chick embryo model, which is similar to first month development in mammals. 100 eggs of 61 ± 5 gr, specific pathogen-free 0 day white fertilized chicken eggs were used. Incubation of 28 hours was maintained at a constant temperature of 37.5 ± 0.5°C, humidity in the range of 60 – 68%. They were divided into 4 groups of 25 eggs each. Liraglutid was administered subblastodermically with a Hamilton micro-injector in 3 different doses. The control group was injected with 0.9% sterile saline, and the experimental groups were injected with liraglutide at doses of 1.5, 7.5 and 15 µg/egg. After the injection, the windows were closed with sterile drape and left for incubation. At the end of 48 hours of incubation, all eggs were hatched and evaluated on the basis of Hamburger-Hamilton scale. In the study, neural tube patency, somite numbers, and Hamburger-Hamilton stages were examined, it was determined that the dose-related difference between the control and experimental groups was not statistically significant (p>0.05). It was determined that the difference between the high dose group and the other groups in terms of fore-aft lengths was statistically significant (P<0.05). As a result, there was no significant relationship between the doses of Liraglutide and neural tube patency and somite counts, but differences were found between fore-aft measurements. Further research is recommended for a clearer understanding of the effects of liraglutide on embryo development.

Keywords

chick embryo model, incretins, liraglutide, neural tube, obesity.

Project Number

20.SAĞ.BİL.33

References

• Akan N. Nöral tüp defektli bebek doğurma riski azaltılabilir. CÜ Hemşirelik Yüksekokulu Dergisi. 2002; 6:42–48.
• Akosman, M.S. Kanatlı Anatomisi. Medipres Yayıncılık, Malatya, Turkey. 2020; pp. 64-67.
• Atay E, Ayekin S, Hatipoğlu RZ, Kural MC, Kuseyri M, Taçyıldız Y, Başoğlu Y, Alkan AB, Bilir A, Ertekin T. The effect of temperature on angiogenesis in chicken embryos. Kocatepe Vet J. 2020; 13(1): 60-68.
• Baggio LL, Drucker DJ. Biology of incretins: GLP-1 and GIP. Gastroenterology, 2007; 132(6): 2131-2157.
• Baker S. Neural tube defects, Greenberg MS, Handbook of Neurosurgery 3rd ed., Florida, Greenberg, 1994; pp. 157-168.
• Briyal S, Shah S, Gulati A. Neuroprotectıve and anti-apoptotic effects of Liraglutid in the rat brain following focal cerebral ischemia, Neuroscience. 2014; 281: 269–281.
• Brocklehurst G. Spina bifida for the clinician (Clinics in Developmental Medicine, No. 57). Lippincott Williams & Wilkins. Philadelphia, USA. 1976.
• Candeias EM, Sebastião IC, Cardoso SM, Correia SC, Carvalho CI, Plácido AI, Santos MS, Oliveira CR, Moreira PI, Duarte AI. Gut-brain connection: The neuroprotective effects of the anti-diabetic drug Liraglutid, World J Diabetes. 2015; 6(6): 807-827.
• Cantini G, Di Franco A, Samavat J, Forti G, Mannucci E, Luconi M. Effect of liraglutid on proliferation and differentiation of human adipose stem cells. Mol Cell Endocrinol. 2015; 402: 43–50.
• Cetinkal A, Colak A, Topuz K, Demircan MN, Simsek H, Berber U, Umur AS, Selcuki M, Vatansever S. The effects of meloxicam on neural tube development in the early stage of chick embryos, Turkish Neurosurgery, 2010; 20(2): 111-116.
• Dady A, Duband JL. Cadherin interplay during neural crest segregation from the non-neural ectoderm and neural tube in the early chick embryo. Dev Dyn. 2017; 246(7): 550-565.
• Daly S, Mills, J.L., Molloy, A.M., Conley, M., Lee, Y.J., Kirke, P.N. Minimum effective dose of folic acid for food fortification to prevent neural-tube defects. The Lancet. 1997; 350: 1666-1669.
• Emon ST, Orakdogen M, Uslu S, Somay H. Effects of the popular food additive sodium benzoate on neural tube development in chicken embryo. Turk Neurosurg. 2015; 25(2): 294-297.
• Ertekin, T., Bilir, A., Aslan, E., Koca, B., Turamanlar, O., Ertekin, A., & Albay, S. The effect of diclofenac sodium on neural tube development in the early stage of chick embryos. Folia morphol. 2019; 78(2): 307-313.
• Gao H, Zeng Z, Zhang H, Zhou X, Guan L, Deng W, Xu L. The glucagon like peptide-1 analogue liraglutid ınhibits oxidative stress and ınflammatory response in the liver of rats with diet-ınduced non-alcoholic fatty liver disease. Biol Pharm Bull. 2015; 38(5): 694-702.
• Inoue T, Inoguchi T, Sonoda N, Hendarto H, Makimura H, Sasaki S, Yokomizo H, Fujimura Y, Miura D, Takayanagi R. GLP-1 analog Liraglutid protects against cardiac steatosis, oxidative stress and apoptosis in streptozotocin-induced diabetic rats, Atherosclerosis. 2015; 240(1): 250-259.
• Jelsing J, Vrang N, Hansen G, Raun K, Tang-Christensen M, Knudsen LB. Liraglutid: short-lived effect on gastric emptying—long lasting effects on body weight. Diabetes Obes Metab. 2012; 14(6): 531–538.
• Kimura T, Kaneto H, Shimoda M, Hirukawa H, Okauchi S, Kohara K, Hamamoto S, Tawaramoto K, Hashiramoto M, Kaku K. Protective effects of pioglitazone and/or Liraglutid on pancreatic β-cells in db/db mice: Comparison of their effects between in an early and advanced stage of diabetes. Mol Cell Endocrinol. 2015; 400: 78–89.
• Kürtül İ. Veteriner Anatomi. İçinde: Sinir Sistemi. Eds: Türkmenoğlu, İ., Demirkan, Ç.A., Özdemir, V., Akosman, M.S. Medipres Yayıncılık, Malatya, Turkey. 2018; pp. 495-498.
• Lee H, Nagele RG, Pietrolungo JF. Toxic and teratologic effects of caffeine on explanted early chick embryos. Teratology. 1982; 25(1): 19-25.
• Lovshin JA, Drucker DJ. Incretin-based therapies for type 2 diabetes mellitus. Nat Rev Endocrinol. 2009; 5: 262–269.
• Mete M, Gurcu B, Collu F, Unlu Unsal U, Duransoy YK, Tuglu MI, Selcuki M. Effects of lacosamide “a novel antiepileptic drug” in the early stages of chicken embryo development. Childs Nerv Syst, 2016; 32(9): 1715-1719.
• Milunsky A. The prenatal diagnosis of neural tube and other congenital defects. In Genetic disorders and the fetus. Springer, Boston, USA. 1986; pp. 453-519
• Özaçmak HS, Bayraktaroğlu T. Glukagon Benzeri Peptid-1’in Sinir Sistemi veİştah Kontrolü Üzerine Etkileri. Turkish J Diabetes Obesity, 2017; 1(1): 1-6.
• Özer F, Demirel A, Dilsiz Ö, Aydın M, Özdemir N, Uyanıkgil Y, Baka M. Effects ofLevetiracetam on neural tube development and closure of the chick embryos in ovo. Childs Nerv Syst. 2012; 28: 969–976. Rasmussen CB, Lindenberg S. The effect of Liraglutid on weight loss in women with polycystic ovary syndrome: an observational study. Front Endocrinol. 2014; 5:140.
• Robert HA. Congenital anomalies of the central nervous system. Eds: Behrman, R.M., Arvin, A.M., Nelson Textbook of Pediatrics 16th ed., Philadelphia, USA. 2000; pp. 1803-1813.
• Rowland CA, Correa A, Cragan JD, Alverson CJ. Are encephaloceles neural tube defects, Pediatrics. 2006; 118: 916–923.
• Song G, Cui Y, Ji-Han Z, Fei-Xia H, Ma X. Effects of choline on sodium arsenite-induced neural tube defects in chick embryos, Food Chem Toxicol. 2012; 50(12): 4364-4374.
• Tunçbilek E, Boduroğlu K, Alikaşifoğlu M. Neural tube defects in Turkey: prevalence, distribution and risk factors. Turkish J Pediatrics. 1999; 41(3): 299-305.
• Tureci E, Asan Z, Eser M, Tanriverdi T, Alkan F, Erdincler P. The effects of valproic acid and levetiracetam on chicken embryos. J Clin Neurosci. 2011; 18(6): 816-820.
• Vatansever HS, Umur AŞ, Inan VS, Selçuki M. The Effects of Methotrexate on the Development of Neural Tube Defects in the Chick Embryo. Turkish J Vet Anim Sci. 2003; 27(5): 1119-1125.
• Vella A, Shah P, Reed A, Adkins A, Basu R, Rizza R. Lack of effect of exendin-4 and glucagon-like peptide-1-(7, 36)-amide on insulin action in non-diabetic humans. Diabetologia. 2002; 45(10): 1410-1415.
• Wang R, Sun DG, Song G, Guan CY, Cui Y, Ma X, Xia HF. Choline, not folate, can attenuate the teratogenic effects of dibutylphthalate (DBP) during early chick embryo development. Environ Sci Pollut Res. 2019; 26(29): 29763-29779.
• Whitsel AI, Johnson CB, Forehand CJ. An in ovo chicken model to study the systemic and localized teratogenic effects of valproic acid. Teratology. 2002; 66(4): 153-163.
• Yerby MS. Clinical care of pregnant women with epilepsy: neural tube defects and folic acid supplementation. Epilepsia. 2003; 44(3): 33-40.
• Yıldız D, Akbayrak N. Nöral tüp defektleri ve önlemede hemşirelik yaklaşımları, Atatürk Üniversitesi Hemşirelik Yüksekokulu Dergisi, 2008; 11: 102–111.
• Zavattaro M, Caputo M, Sama MT, Mele C, Chasseur L, Marzullo P, Pagano L, Mauri MG, Ponziani MC, Aimaretti G, Prodam F. One-year treatment with Liraglutid improved renal function in patients with type 2 diabetes: a pilot prospective study. Endocrine. 2015; 50(3): 620-626.