Investigation of Inhibition Effect of Oxytocin on Carbonic Anhydrase and Acetylcholinesterase Enzymes in the Heart Tissues of Rats

Yıl 2018, Cilt: 8 Sayı: 1, 199 - 207, 31.03.2018

Ümit Muhammet Koçyiğit

https://doi.org/10.21597/jist.407875

Cited By: 7

Öz

In our study, it was aimed to investigate the effects of oxytocin, oxytocin receptor antagonist

atosiban and oxytocin-atosiban injected to rats on carbonic anhydrase (CA) and acetylcholinesterase (AChE)

enzyme activities in the heart of rats. For this purpose, four different groups (n = 6) consisting of a total of 24

rats, were formed. (Control group, oxytocin treated group, atosiban treated group, and oxytocin and atosiban

combination treated group). The rats were necropsied after 60 minute intraperitoneal injection of the chemicals into

the rats. Cardiac tissue of rats was removed. The enzyme activity averages of the groups are statistically compared.

According to this, while the activity of carbonic anhydrase enzyme in heart tissue of rats decreases in oxytocin

and atosiban given groups, in the combination group with oxytocin and atosiban it was seen that the reduction

was relatively less according to the others. Acetylcholinesterase activity decreases in both groups of oxytocin and

atosiban which given groups did not show any significant change in the group in which oxytocin and atosiban were

given together.

Anahtar Kelimeler

enzyme activity, carbonic anhydrase, oxytocin, rat

Sıçanların Kalp Dokusunda Oksitosin’in Karbonik Anhidraz ve Asetilkolinesteraz Enzimleri Üzerine İnhibisyon Etkisinin Araştırılması

Öz

Çalışmamızda, sıçanlara enjekte edilen oksitosin, oksitosin reseptör antagonisti atosiban ve oksitosinatosiban

hormonlarının, sıçanların kalp dokusunda karbonik anhidraz (CA) ve asetilkolinesteraz (AChE) enzim

aktivitelerine etkilerinin incelenmesi amaçlanmıştır.Bu amaçla, toplam 24 adet sıçandan oluşan dört farklı grup

(n=6) oluşturuldu. (Kontrol grubu, oksitosin verilen grup, atosiban verilen grup ve oksitosin ile atosiban’ın birlikte

verildiği grup). Sıçanlara kimyasallar intraperitoneal olarak enjekte edildikten 60 dakika sonra sıçanlar nekropsiye

alındı. Sıçanların kalp dokuları çıkarıldı. Elde edilen her bir enzim için aktivite değerleri istatistiksel olarak

hesaplandı.

Buna göre sıçanların kalp dokusunda karbonik anhidraz enzim aktivitesi oksitosin ve atosiban verilen gruplarda

azalışa neden olurken, oksitosin ile atosibanın birlikte verildiği grupta ise azalmanın diğerlerine nispeten daha az

olduğu görüldü. Oksitosin ve atosiban verilen gruplarda asetilkolinesteraz aktivitesinde görülen azalma, oksitosin

ve atosiban’ın birlikte verildiği grupta gözlenmedi.

Anahtar Kelimeler

enzim aktivitesi, karbonik anhidraz, oksitosin, rat

Kaynakça

• Akıncıoglu A, Topal M, Gulcin I, and Goksu S, 2014. Novel sulphamides and sulphonamides incorporating the tetralin scaffold as carbonic anhydrase and acetylcholine esterase inhibitors. Archiv der Pharmazie, 347(1), 68-76.
• Armstrong JM, Myers DV, Verpoorte JA and Edsall JT, 1966. Purification and properties of human erythrocyte carbonicanhydrase. J. Biol. Chem, 214, 5137
• Asad M, Shewade DG, Koumaravelou K, Abraham BK, Vasu S, Ramaswamy S, 2001. Gastric antisecretory and antiulcer activity of oxytocin in rats and guinea pigs. Life Sci.,70: 17.
• Authier S, Tanguay JF, Geoffroy P, Gauvin D, Bichot S, Ybarra N, Otis C, Troncy E. Cardiovascular effects of oxytocin infusion in a porcine model of myocardial infarct. J. Cardiovasc. Pharmacol. 2009.
• Berg JM, Tymoczko JL, Stryer L, 2014. Biyokimya. Palme Yayıncılık.241-247p, Ankara.
• Bhatt A, Mahon BP, Cruzeiro VWD, Cornelio B, Laronze‐Cochard M, Ceruso M, ... & Roitberg A, 2017. Structure–Activity Relationships of benzenesulfonamide‐Based Inhibitors towards Carbonic Anhydrase Isoform Specificity. Chembiochem, 18(2), 213-222.
• Black LV, Ness TJ, Robbins MT. 2009, Effects of oxytocin and prolactinon stress-induced bladder hypersensitivity in female rats. J Pain ,10: 1065-72.
• Ellman GL, Courtney KD, Andres V, & Featherstone RM, 1961. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochemical pharmacology, 7(2), 88IN191-9095.
• Erbas O, Yılmaz M, Anil H, Bora S, Evren V, Peker G,2013. Peptides Oxytocin inhibits pentylentetrazol- induced seizures in the rat. Peptides, 40:141-144.
• Favaretto AL, Ballejo GO, Albuquerque-Araújo WI, Gutkowska J, Antunes-Rodrigues J, McCann SM, 1997. Oxytocin releases atrial natriuretic peptide from rat atria in vitro that exerts negative inotropic and chronotropic action. Peptides ,18: 1377-1381.
• Gocer H, Akincioglu A, Goksu S, Gulcin İ, & Supuran CT,2015. Carbonic anhydrase and acetylcholinesterase inhibitory effects of carbamates and sulfamoylcarbamates. Journal of enzyme inhibition and medicinal chemistry, 30(2), 316-320.
• Gocer H, Topal F, Topal M, Kuçuk M, Teke D, Gulcın I., ... and Supuran CT, 2016. Acetylcholinesterase and carbonic anhydrase isoenzymes I and II inhibition profiles of taxifolin .Journal of enzyme inhibition and medicinal chemistry, 31(3), 441-447.
• Gul HI, Mete E, Taslimi P, Gulcin I, .. and Supuran CT, 2017. Synthesis, carbonic anhydrase I and II inhibition studies of the 1, 3, 5-trisubstituted-pyrazolines. Journal of enzyme inhibition and medicinal chemistry, 32(1), 189-192.
• Gulcın I, Beydemir S, … and Buyukokuroğgu ME, 2004. In vitro and in vivo effects of dantrolene on carbonic anhydrase enzyme activities. Biological and Pharmaceutical Bulletin, 27(5), 613-616.
• Houshmand F, Faghihi M and Zahediasl S, 2009. Biphasic protective effect of oxytocinon cardiac ischemia/reperfusion injury in anaesthetized rats. Peptides, 30(12), 2301-2308.
• Huyut Z, Beydemir S, Gulcin I, 2016a. Inhibitory effects of some phenolic compounds on the activities of carbonic anhydrase: from in vivo to ex vivo. Journal of Enzyme Inhibition and Medicinal Chemistry, 31(6), 1234-1240.
• Huyut Z, Sekeroğlu MR, Balahoroglu R, Karakoyun T, Çokluk E, 2016b. The Relationship of Oxidation Sensitivity of Red Blood Cells and Carbonic Anhydrase Activity in Stored Human Blood; Effect of Certain Phenolic Compounds. BioMed Research International, Volume 2016, , http://dx.doi.org/10.1155/2016/3057384.
• Ivell R, Russel JA,1995. Oxytocin, Cellular and Molecular Approaches in Medicine and Research. Plenum Press, New York, p:259-268.
• Jankowski M, Danalache B, Wang D, Bhat P, Hajjar F. Marcinkiewicz, M, Paquin J, McCann SM, Gutkowska J, 2004. Oxytocin in cardiac ontogeny. Proc. Natl. Acad. Sci. USA , 101: 13074- 13079.
• Jezdinsky J, Stojan B, Queisnerova M, 1963. Demonstration of the existance of an anti-inflammatory factor situated in the posterior pituitary. Arch. Int. Pharmacodyn. Ther,146: 561-578.
• Kocyigit UM, Aslan ON, Gulcin I, Temel Y, & Ceylan M, 2016. Synthesis and Carbonic Anhydrase Inhibition of Novel 2‐(4‐(Aryl) thiazole‐2‐yl)‐3a, 4, 7, 7a‐tetrahydro‐1H‐4, 7‐methanoisoindole‐1, 3 (2H)‐dione Derivatives. Archiv der Pharmazie, 349(12), 955-963.
• Kocyigit UM, Taskıran A,Taslimi P,Yokus A,Gulcın I, 2017. nhibitory effects of Oxytocin and Oxytocin Receptor Antagonist Atosiban on the Activities of Carbonic Anhydrase and Acetylcholinesterase Enzymes in the Liver and Kidney Tissues of Rats. Journal of Biochemical and Molecular Toxicology, DOI: 10.1002/jbt.21972.
• Kose LP, Gulcın I, Goren AC, Namiesnik J, Martinez-Ayala AL, & Gorinstein S, 2015. LC–MS/MS analysis, antioxidant and anticholinergic properties of galanga (Alpinia officinarum Hance) rhizomes. Industrial Crops and Products, 74, 712-721.
• Kucukoglu K, Oral F, Aydin T, Yamali C, Algul O, Sakagami H, ... and Gul HI, 2016.Synthesis, cytotoxicity and carbonic anhydrase inhibitory activities of new pyrazolines. Journal of Enzyme Inhibition and Medicinal Chemistry, 31(sup4), 20-24.
• Maren TH, 1960. A simplifieldmicromethodforthedetermination of carbonicanhydrase and its inhibitors. Journal of Pharmacologyand Experimental Therapeutics, 130, 26.
• Marshall JJ, 1970. Chromatog 53,379.
• Miki T, Miura T, Tanno M, Nishihara M, Naitoh K, Sato T, Takahashi A, Shimamoto K, 2007. Impairment of cardioprotective PI3K-Akt signaling by post-infarct ventricular remodeling is compensated by an ERK-mediated pathway. Basic Res. Cardiol,102: 163-170.
• Miki T, Miura T, Tanno M, Nishihara M, Naitoh K, Sato T, Takahashi A, Shimamoto K, 2009. Postinfarct treatment with oxytocin improves cardiac function and remodeling via activating cellsurvival signals and angiogenesis. J. Cardiovasc. Pharmacol,102(2):163-70.
• Neumann ID, 2002.Involvement of the brain oxytocin system in stress coping: interactions with the hypothalamo-pituitaryadrenal axis. Prog Brain Res ,139: 147–62.
• Ondrejcakova M, Ravingerova T, Bakos J, Pancza D, Jezova D, 2009. Oxytocin exerts protective effects on in vitro myocardial injury induced by ischemia and reperfusion. Can. J. Physiol. Pharmacol,87: 137-142.
• Ozbey F, Taslimi P, Gulcın İ, Maraş A, Goksu S, & Supuran CT,2016. Synthesis of diaryl ethers with acetylcholinesterase, butyrylcholinesterase and carbonic anhydrase inhibitory actions. Journal of enzyme inhibition and medicinal chemistry, 31(sup2), 79-85.
• Paquin J, Danalache BA, Jankowski M, McCann SM, Gutkowska J, 2002. Oxytocin induces differentiation of P19 embryonic stem cells to cardiomyocytes. Proc. Natl. Acad. Sci. USA , 99: 9550-9555.
• Petersson M, Uvnäs-Moberg K, 2008. Postnatal oxytocin treatment of spontaneously hypertensive male rats decreases blood pressure and body weight in adulthood. Neurosci Lett ,440:166-169.
• Pullan LM and Noltmann EA, 1985. Purification and properties of pig muscle carbonic anhydrase III. Biochimica et Biophysica Acta, 839, 147-54.
• Rıcklı EE, Ghazanfar SAS, Gibbons BH and Edsall JT, 1964. Carbonic anhydrase from human erythrocytes. Journal of Biological Chemistry, 239, 1065.
• Sanu O and Lamont RF,2010 . Critical appraisal and clinical utility of atosiban in the management of preterm labor. Therapeutics and clinical risk management, 6, 191.
• Sımsek Y, Celik O, Karaer A, et al., 2012: Elevated cardiac oxidative stress in newborn rats from mothers treated with atosiban. 655-661.
• Sır G, Arısu E, Yiğittürk G, Çavuşoğlu T, Avcı ÇB, Çelik S, … and Uyanıkgil Y,2015. Oksitosinin hücresel tedavide kullanılma potansiyeli. İstanbul Bilim Üniversitesi Florence Nightingale Tıp Dergisi, 1(3).
• Soares TJ, Coimbra TM, Martins AR, Pereira AG, Carnio EC, Branco LG, Albuquerque-Araujo WI, de Nucci G, Favaretto AL, Gutkowska J, McCann SM, Antunes-Rodrigues J, 1999. Atrial natriuretic peptide and oxytocin induce natriuresis by release of cGMP. Proc. Natl. Acad. Sci. USA, 96: 278-283.
• Taslimi P, Gulcin I, Ozgeris B, Goksu S, Tumer F, Alwasel SH, & Supuran CT,2016. The human carbonic anhydrase isoenzymes I and II (hCA I and II) inhibition effects of trimethoxyindane derivatives. Journal of enzyme inhibition and medicinal chemistry, 31(1), 152-157.
• Verpoorte JA, 1967. EsteraseActivities of Human CarbonicAnhydrases B and C Mehta S, Edsall J.T. J.Biol. Chem, 242, 4221-4229.
• Viero C, Shibuya I, Kitamura N, Verkhratsky A, Fujihara H, Katoh A, Ueta Y, Zingg HH, Chvatal A, Sykova E, Dayanithi G, 2010. Oxytocin: Crossing the bridge between basic science and pharmacotherapy. CNS Neurosci Ther ,16: e138-56.
• Wilbur KM. and Anderson NG, 1948. Electrometric and colorimetric determination of carbonic anhydrase. Journal of Biological Chemistry, 176, 147-154.
• Wistrand PJ, 2002. Carbonic anhydrase III in liver and muscle of male rats purification and properties. Upsala Journal of Medicinal Sciences, 107, 77-88.
• Yegen BC, 2010. Oxytocin and hypothalamo-pituitaryadrenal axis. Marmara Pharma J ,14: 61-6.