Effect of ondansetron application on neural tube development in 48-hour chick embryos
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Keywords:Chicken embryo, ondansetron, mRNA, neural tube defect
The study aims to show that ondansetron, which is used safely in pregnant women, can cause serious side effects. Neural tube defects are among the most common congenital malformations of the central nervous system. It is known that genetic predisposition, environmental factors, and some drugs play an important role in the development of neural tube defects. Ondansetron is a selective 5-hydroxytryptamine-3 receptor antagonist used in the treatment of cancer, nausea, and vomiting during pregnancy and after anesthesia. In the literature studies, it was not found that developmental anomalies were observed. Seventy-five free specific pathogen eggs were incubated for 32 hours and divided into five groups of 15 eggs each, including a control group. Ondansetron was administered to these five groups by sub-blastoderm route in 4 different doses with a Hamilton microinjector. At 48 hours of incubation, the embryos were dissected and examined morphologically and histopathologically. At the end of the study, a significant dose-dependent decrease was observed in crown-rump lengths, somite numbers, and mean the number of silver-dyed nucleolar regulatory regions (AgNOR) and total AgNOR / nuclear area ratios. Statistically significant differences were observed between the experimental groups in terms of neural tube closure (p <0.05). Ondansetron has been shown to affect neuronal development and vertebral growth in chicken embryos depending on increasing doses.
Siminerio LL, Bodnar LM, Venkataramanan R, Caritis SN. Ondansetron use in pregnancy. Obstet Gynecol. 2016;127(5):873-7. doi: 10.1097/AOG.0000000000001375.
Practice Bulletin No. 153: Nausea and vomiting of pregnancy. Obstet Gynecol. 2015;126(3):12-24. doi: 10.1097/AOG.0000000000001048.
Mitchell AA, Gilboa SM, Werler MM, Kelley KE, Louik C, Hernández-Díaz S, et al. Medication use during pregnancy, with particular focus on prescription drugs: 1976-2008. Am J Obstet Gynecol. 2011;205:51.1-8. doi: 10.1016/j.ajog.2011.02.029.
Abas MN, Tan PC, Azmi N, Omar SZ. Ondansetron compared with metoclopramide for hyperemesis gravidarum: A randomized controlled trial. Obstet Gynecol. 2014;123:1272-9.
Kashifard M, Basirat Z, Kashifard M, Golsorkhtabar-Amiri M, Moghaddamnia A. Ondansetrone or metoclopromide? Which is more effective in severe nausea and vomiting of pregnancy? A randomized trial double-blind study. Clin Exp Obstet Gynecol. 2013;40:12-30.
Song G, Cui Y, Han ZJ, Xia HF, Ma X. Effects of choline on sodium arsenite-induced neural tube defects in chick embryos. Food Chem Toxicol. 2012;50:4364-74. doi: 10.1016/j.fct.2012.08.023.
Ertekin T, Bilir A, Aslan E, Koca B, Turamanlar O, Ertekin A, et al. The effect of diclofenac sodium on neural tube development in the early stage of chick embryos. Folia Morphol (Warsz). 2019;78:307-13. doi: 10.5603/FM.a2018.0080.
Pfaffl MW, Horgan GW, Dempfle L. Relative Expression Software Tool (REST) for group wise comparison and statistical analysis of relative expression results in real-time PCR. Nucleic Acids Res. 2002;30:36. doi: 10.1093/nar/30.9.e36.
Mayhall EA, Gray R, Lopes V, Matteson KA. Comparison of antiemetics for nausea and vomiting of pregnancy in an emergency department setting. Am J Emerg Med 2015;33:882-6. doi: 10.1016/j.ajem.2015.03.032.
Andrade C. Major congenital malformation risk after first trimester gestational exposure to oral or intravenous Ondansetron. J Clin Psychiatry 2020;81(3):20f13472. doi:10.4088/JCP.20f13472.
Collins KL, Wilson M, Vincent EC, Safranek S. How safe and effective is ondansetron for nausea and vomiting in pregnancy? J Fam Pract. 2019;68(7):12-E14.
Anderka M, Mitchell AA, Louik C, Werler MM, HernándezDiaz S, Rasmussen SA, et al. Medications used to treat nausea and vomiting of pregnancy and the risk of selected birth defects. Birth Defects Res A Clin Mol Teratol. 2012;94:22-30. doi: 10.1002/bdra.22865.
Pasternak B, Svanstrom H, Hviid A. Ondansetron in pregnancy and risk of adverse fetal outcomos. N Engl J Med. 2013;368:814-23. doi: 10.1056/NEJMoa1211035.
Danielsson B, Wikner BN, Kallen B. Use of ondansetron during pregnancy and congenital malformations in the infant. Reprod Toxicol. 2014;50:134-7. doi: 10.1016/j.reprotox.2014.10.017.
Damkier P, Kaplan YC, Shechtman S, Diav-Citrin O, Cassina M, Schoendorfer CW, et al. Ondansetron should never be used in pregnancy: Against: Ondansetron in pregnancy revisited. BJOG. 2021;128(1):111-2. doi: 10.1111/1471-0528.16476.
Guvenc Y, Dalgic A, Billur D, Aydin S, Daglioglu E, Ozdol O, et al. The effects of levetiracetam on neural tube development in the early stage of chick embryos. Turk Neurosurg. 2013;23:617- 22. doi: 10.5137/1019-5149.JTN.7471-13.0.
Atay E, Ertekin A, Bozkurt E, Aslan E. Impact of bisphenol A on neural tube development in 48-hr chicken embryos. Birth Defects Res. 2020;112:1386-96. doi: 10.1002/bdr2.1791.
Derenzini M, Trerè D. Standardization of interphase Ag-NOR measurement by means of an automated image analysis system using lymphocytes as an internal control. J Pathol. 1991;165:337-42. doi: 10.1002/path.1711650410.
Ertekin T, Bozkurt O, Eroz R, Nisari M, Bircan D, Nisari M, et al. May argyrophilic nucleolar organizing region-associated protein synthesis be used for selecting the most reliable dose of drugs such as rhamnetin in cancer treatments? Bratisl Lek Listy. 2016;117:653-8. doi: 10.4149/bll_2016_126.
Rakip U, Bilir A, Arikan ES. Effect of pethidine hydrochloride on the development of neural tube: A genetic analysis study in a chick embryo model. World Neurosurg. 2021;150:613-620. doi: 10.1016/j.wneu.2021.03.065.
Wang G, Li Y, Wang XY, Chuai M, Chan SYH, Lei J, et al. Misexpression of BRE gene in the developing chick neural tube affects neurulation and somitogenesis. Mol Biol Cell. 2015;26:978-92. doi: 10.1091/mbc.E14-06-1144.
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