INVESTIGATION OF THE ACTION MECHANISM OF AMMONIUM PYRROLIDINE DITHIOCARBAMATE ON RAT TRACHEA SMOOTH MUSCLE CONTRACTION-RELAXATION RESPONSE

Year 2020, Issue: 045, 12 - 27, 31.12.2020

Hayri Dayıoğlu Ayhan Yılmaz Merve Aktaş Fatih Alan Sinan Darcan

Abstract

Ammonium pyrrolidine dithiocarbamate (APDTC) is a suppressive thiol compound of Nuclear Factor kappa B (NF-κB) and works to prevent infections, regulate oxidation, prevent cell death, affects on viruses. Therefore, it is recommended to avoid harmful practices and to give importance to active substance research in medical ethics. In postoperative care, respiratory system relaxation treatments are important. There is insufficient research into how the functions of APDTC are regulated in human and animals. In our study, we aimed to evaluate the function of APDTC in rat trachea smooth muscle. 70 male Wistar albino rats were used. The rats were euthanized by giving anesthesia and after applying cervical dislocation the trachea was separated, connective tissues of trachea were separated and placed in Krebs solution. Potassium chloride (KCl), Acetylcholine (ACh), APDTC, Atropine, Phentolamine, Propranolol, Nifedipine and Tetraethylammonium (TEA) were added in to the solution. Eventually, APDTC produced a relaxation response in the tracheal smooth muscle induced by ACh, but this relaxation was not statistically significant. In our study, Half maximal effective concentration (EC50) dose was found to be ineffective. APDTC did not induce L-type Ca2+ channel and K+ channel receptors to differentiate relaxation response by producing a cholinergic-adrenergic effect. We think that APDTC did not affect these channels. Further studies with the use of different doses are recommended.

Keywords

APDTC, trachea, adrenergic, cholinergic, Ca2+ channels, K+ channels

References

• [1] Bölüm Yazarlığı: Kunter, E., (2007). Astım Epidemiyolojisi. In: Kartaloğlu Z, Kunter E (editörler). Astım. İstanbul: Mart Matbaacılık Sanatları, Bölüm Yazarlığı, ISBN: 975-8408-36-4.
• [2] Derneği, T. T. (2010). Astım Tanı ve Tedavi Rehberi. Turkish Thoracic J,11, 6-60.
• [3] Mercan. V., (2015). Sıçan Trakea’sı Düz Kası Kasılma-Gevşeme Yanıtları Üzerine Ammonium Pyrrolidine Dithiocarbamate, SG-Benz, Caffeic Acid Phenil Ester, Atorvastatin Kalsiyum’un etkileri. Yüksek lisans tezi, Dumlupınar üniversitesi fen bilimleri enstitüsü, Kütahya, s.1-29.
• [4] Mitchell, H. W. (1987). Electromechanical effects of tetraethylammonium and K+ on histamine-induced contraction in pig isolated tracheal smooth muscle. Lung,165(1), 129-142.
• [5] Şahin, A.S., Atalık, K.E., Kılıç, M., Doğan, N. (1999).Tavşan Trachea Düz Kasında Β-Adrenerjik Reseptör Agonistleri ve Fosfodiesteraz İnhibitörlerinin Gevşetici Etkilerinde K+ -Kanallarının Rolü, Selçuk Üniversitesi Tıp Fakültesi Farmakoloji Anabilim Dalı Dergisi; 15: 173-177.
• [6] Webb, R. C. (2003). Smooth muscle contraction and relaxation. Advances in physiology education, 27(4), 201-206.
• [7] Guyton, A. C.and Hall, J. E. (2007). Tıbbi Fizyoloji. 11.Basım. Nobel Tıp Kitabevleri, 837, 1056-7.
• [8] Akçay, M., (1971). Kas Fizyolojisi Ders Kitabı, Güven Matbaası, Ankara, s. 20-25.
• [9] Terzioglu, M. and Çakar, L. (1989). Fizyoloji Ders Kitabı, Basım Atölyesi: İstanbul, s 106-111.
• [10] Banli, O. and Unal, A. (1989). Fizyoloji Ders Notları. Metay Medikal Yayıncılık: Ankara, s. 38-45.
• [11] Ganong, F. W.(1995). Tıbbi Fizyoloji, Barış Kitabevi, Çeviri Editörü: A. Doğan, İstanbul, s.85-121.
• [12] Gökmen, F. G. (2003). Sistematik anatomi. İzmir, İzmir Güven Kitabevi, 67-197.
• [13] Aydilek, R., Kartaloğlu,Z., Taşkapan, O., Işitmangil, G., Kunter, E., Küçükardalı Y. and Günen, H. (2007). Astım, Ankara; Ofset Hazırlık, s 1-191.
• [14] Kartaloğlu, Z., Okutan, O., (2013). Solunum sistemi fonksiyonel Değerlendirilmesi. Deomed; İstanbul, s.1-7.
• [15] Barnes, P. J. (1996). NO or no NO in asthma, Thorax, 51(2), 218-220.
• [16] Özkan, M. Yüksekol İ. (2003). Nitrik oksit ve akciğerler. Toraks dergisi, 4(1), 88-94.
• [17] Saygin, M., ve Naziroğlu, M. (2010) TRPM2 Katyon Kanallarının Aktivasyonunda Rol Oynayan Moleküler Mekanizmalardaki Son Gelişmeler. Journal of Experimental and Clinical Medicine, 27(2), 42-45.
• [18] Özgül, C. (2015). Protein Kinaz C Aktivatörü PMA’nın TRPV1 Kanalları Üzerindeki Etkileri. Hacettepe University Journal of the Faculty of Pharmacy, s 42-73.
• [19] Mahrebel, A. A. (2018). Aç farelerde atropin ve yem ile oluşan konvülssiyonlara uzun süre haloperidol verilmesinin, olanzapinin ve antiepileptiklere amitriptilin eklenmesinin etkilerinin araştırılması, s.1-32.
• [20] McCleskey, E. W., Fox, A. P., Feldman, D. ve Tsien, R. W. (1986). Different types of calcium channels, Journal of Experimental Biology, 124: 177-90.
• [21] Katzung, B. G., Masters, S. B. and Trevor, A. J., (2012). Basic & Clinical Pharmacology, 12. Baskı, McGraw-Hill Higher Education, s. 87, 152.
• [22] Guyton, A. C. and Hall, J. E. (2013). Tıbbi Fizyoloji (çev. Yeğen, B.), 12. Baskı, Nobel Tıp Kitabevleri, s. 91, 307, 308, 731, 773.
• [23] DiPalma, J. R. (1986).Temel Tıp Farmakolojisi. Nobel Tıp Kitabevi, s.248-310.
• [24] Bökesoy, T. A., Çakıcı, İ. and Melli, M. (2000). Farmakoloji Ders Kitabı, Ankara: Gazi Kitabevi Yayınları, s. 46, 165.
• [25] Thorneloe, K.S. and Nelson, M. T. (2005). Ion channels in smooth muscle: regulators of intracellular calcium and contractility, Canadian Journal of Physiology and Pharmacology, 83: 215–242.
• [26] Bisset, D. and Chung, S. H. (2008) .Efficacy of external tetraethylammonium block of the KcsA potassium channel: Molecular and Brownian dynamics studies, Biochimica et Biophysica Acta (BBA) -Biomembranes, 1778(10): 2273-82.
• [27] Pan, W. Z., Du, J., Zhang, L. Y. and Ma, J. H., (2018). The roles of NF-kB in the developpment of lung injury after one-lung ventilation, European Review for Medical and Pharmacological Sciences, 22(21): 7414-7422.
• [28] Kinoshita, K., Sato, K., Hori, M., Ozaki, H. and Karaki, H. (2003). Decrease in activity of smooth muscle L-type Ca2+ channels and its reversal by NF-κB inhibitors in Crohn's colitis model. American Journal of Physiology-Gastrointestinal and Liver Physiology, 285(3): G483-G493.
• [29] Marshall, P. B. (1955). Antagonism of acetylcholine by (+) and (‐) hyoscyamine. British Journal of Pharmacology,10(3), 354-355.
• [30] Murray, M. A., Boyle, J. P. and Small, R. C. (1989). Cromakalim induced relaxation of guinea pig isolated trachealis: antagonism by glibenclamide and by phentolamine. British journal of pharmacology, 98(3), 865-874.
• [31] Barnes, P. J. (1985). Clinical studies with calcium antagonists in asthma. British journal of clinical pharmacology, 20(S2), 289S-298S.
• [32] Hsu, H. T., Yang, Y. L., Chen, W. C., Chen, C. M., and Ko, W. C. (2014). Butylidenephthalide blocks potassium channels and enhances basal tension in isolated guinea-pig trachea. BioMed research international, s.1-7.
• [33] Chabicovsky, M., Prieschl-Grassauer, E., Seipelt, J., Muster, T., H. J. Szolar, O., Hebar, A. and Doblhoff-Dier, O. (2010). Pre-Clinical Safety Evaluation of Pyrrolidine Dithiocarbamate. Basic & Clinical Pharmacology & Toxicology, 107, 758–767. Doi: 10.1111/j.1742-7843.2010.00573.x
• [34] Gao S, Jia JY, Yan TK, Yu YM, Shang WY, Wei L, Zheng ZF, Fang P, Chang BC, Lin S. (2016). Effects of ammonium pyrrolidine dithiocarbamate (PDTC) on osteopontin expression and autophagy in tubular cells in streptozotocin-induced diabetic nephropathy rat. Chinese Journal of Medical Science, 96( 44 ): 3590-3595. DOI: 10.3760/cma.j.issn.0376-2491.2016.44.012
• [35] Yang, H., Ma, S. C., Guo, Y., Cui, D. L., and Yao, J. F. (2019). Bidirectional Effects of Pyrrolidine Dithiocarbamate on Severe Acute Pancreatitis in a Rat Model. Dose-Response:An International Journal, s.1-7. DOI: 10.1177/1559325819825905
• [36] Erdem, Ali Onur; Erel, Varlık K.; O., Özlem Girit; Erdoğan, Hasan; Özkısacık, Sezen; Yazıcı, Mesut. (2020). Effects of Local Anesthetics on Smooth Muscle Tissue in Rat Trachea: An In Vitro Study. Turk Toraks Dergisi / Turkish Thoracic Journal. Jul2020, Vol. 21 Issue 4, p223-227. 5p. DOI: 10.5152/TurkThoracJ.2019.19016.
• [37] Wei, Yuan-Yuan; Xuan, Xiu-Chen; Zhang, Xi-Yue; Guo, Ting-Ting; Dong, De-Li. (2019). Niclosamide ethanolamine induces trachea relaxation and inhibits proliferation and migration of trachea smooth muscle cells. European Journal of Pharmacology. 853:229-235. DOI: 10.1016/j.ejphar.2019.03.047.
• [38] Bouhedja, Mourad; Peres, Basile; Fhayli, Wassim; Ghandour, Zeinab; Boumendjel, Ahcène; Faury, Gilles; Khelili, Smail. (2018). Design, synthesis and biological evaluation of novel ring-opened cromakalim analogues with relaxant effects on vascular and respiratory smooth muscles and as stimulators of elastin synthesis. European Journal of Medicinal Chemistry. 144:774-796. DOI: 10.1016/j.ejmech.2017.12.071.
• [39] Parastoo Jafarzade, Seyyed Mohammad Mohseni Mehran, Hassan Moladoust, Mohammad Reza Norasfard, Ahmad Ghorbani, Mahmood Abedinzade. (2018). Effect of Hydroalcoholic Extract of Anethum graveolens L. Seed on Tracheal Smooth Muscle Contractions in Male Rats. Journal of Mazandaran University of Medical Sciences (JMUMS). Vol. 28 Issue 160, p146-150.
• [40] Chang, Hung-Chi; Chen, Shin-Yan; Huang, Yu-Feng; Liu, Feng-Lin; Cherng, Yih-Giun; Wang, Hsing-Won. (2015). Effects of levobupivacaine on isolated rat tracheal smooth muscle. Journal of Anesthesia. Vol. 29 Issue 5, p809-812. DOI: 10.1007/s00540-015-2026-8.
• [41] Gharib-Naseri, Mohammad Kazem; Saberi, Shadan; Mard, Seyyed Ali; Latifi, Seyyed Mahmood. (2012). Bronchodilatory Effect of Hydrogen Sulfide in Rat. Iranian Journal of Basic Medical Sciences. Vol. 15 Issue 4, p907-915.