open access

Vol 78, No 2 (2019)
Original article
Submitted: 2018-06-04
Accepted: 2018-07-09
Published online: 2018-08-31
Get Citation

The effect of diclofenac sodium on neural tube development in the early stage of chick embryos

T. Ertekin1, A. Bilir1, E. Aslan2, B. Koca3, O. Turamanlar1, A. Ertekin4, S. Albay5
·
Pubmed: 30178461
·
Folia Morphol 2019;78(2):307-313.
Affiliations
  1. Department of Anatomy, University of Afyon Kocatepe, School of Medicine, Afyonkarahisar, Turkey
  2. Department of Histology and Embryology, University of Afyon Kocatepe, School of Medicine, Afyonkarahisar, Turkey
  3. Department of Biochemistry, University of Afyon Kocatepe, School of Medicine, Afyonkarahisar, Turkey
  4. Emergency Medicine, Afyonkarahisar State Hospital, Afyonkarahisar, Turkey
  5. Department of Anatomy, Faculty of Medicine, Süleyman Demirel University, Isparta, Turkey

open access

Vol 78, No 2 (2019)
ORIGINAL ARTICLES
Submitted: 2018-06-04
Accepted: 2018-07-09
Published online: 2018-08-31

Abstract

Background: Neural tube defects are congenital malformations of the central nervous system. Genetic predisposition and some environmental factors play an important role in the development of neural tube defects. This study aimed to investigate the effects of diclofenac sodium on the neural tube development in a chick embryo model that corresponds to the first month of vertebral deve- lopment in mammals. 

Materials and methods: Seventy-five fertile, specific pathogen-free eggs were incubated for 28 h and were divided into five groups of 15 eggs each. Diclofenac sodium was administered via the sub-blastodermic route at this stage. Incubation was continued till the end of the 48th h. All eggs were then opened and embryos were dissected from embryonic membranes and evaluated morphologically and histopathologically. 

Results: It was determined that the use of increasing doses of diclofenac sodium led to defects of midline closure in early chicken embryos. There were statistically significant differences in neural tube positions (open or close) among the groups. In addition; crown–rump length, somite number were significantly decreased in high dose experimental groups compared with control group. 

Conclusions: This study showed that development of neurons is affected in chi- cken embryos after administration of diclofenac sodium. The exact teratogenic mechanism of diclofenac sodium is not clear; therefore it should be investigated. 

Abstract

Background: Neural tube defects are congenital malformations of the central nervous system. Genetic predisposition and some environmental factors play an important role in the development of neural tube defects. This study aimed to investigate the effects of diclofenac sodium on the neural tube development in a chick embryo model that corresponds to the first month of vertebral deve- lopment in mammals. 

Materials and methods: Seventy-five fertile, specific pathogen-free eggs were incubated for 28 h and were divided into five groups of 15 eggs each. Diclofenac sodium was administered via the sub-blastodermic route at this stage. Incubation was continued till the end of the 48th h. All eggs were then opened and embryos were dissected from embryonic membranes and evaluated morphologically and histopathologically. 

Results: It was determined that the use of increasing doses of diclofenac sodium led to defects of midline closure in early chicken embryos. There were statistically significant differences in neural tube positions (open or close) among the groups. In addition; crown–rump length, somite number were significantly decreased in high dose experimental groups compared with control group. 

Conclusions: This study showed that development of neurons is affected in chi- cken embryos after administration of diclofenac sodium. The exact teratogenic mechanism of diclofenac sodium is not clear; therefore it should be investigated. 

Get Citation

Keywords

diclofenac sodium; chick embryo; neural tube defect; development

About this article
Title

The effect of diclofenac sodium on neural tube development in the early stage of chick embryos

Journal

Folia Morphologica

Issue

Vol 78, No 2 (2019)

Article type

Original article

Pages

307-313

Published online

2018-08-31

Page views

4151

Article views/downloads

2498

DOI

10.5603/FM.a2018.0080

Pubmed

30178461

Bibliographic record

Folia Morphol 2019;78(2):307-313.

Keywords

diclofenac sodium
chick embryo
neural tube defect
development

Authors

T. Ertekin
A. Bilir
E. Aslan
B. Koca
O. Turamanlar
A. Ertekin
S. Albay

References (45)
  1. Akter R, Sarker M. Effect of diclofenac sodium in broilers. Bangl J Vet Med. 2015; 13(1): 19–24.
  2. Andreasson KI, Savonenko A, Vidensky S, et al. Age-dependent cognitive deficits and neuronal apoptosis in cyclooxygenase-2 transgenic mice. J Neurosci. 2001; 21(20): 8198–8209.
  3. Arslan H, Aktaş A, Elibol E, et al. Effects of prenatal diclofenac sodium exposure on newborn testis: a histomorphometric study. Biotech Histochem. 2016; 91(4): 277–282.
  4. Barutcuoglu M, Selcuki M, Vatansever S, et al. The effects of ethanol on neural tube development in early stage neural tube development chick embryos. Türk Nöroşir Derg. 2001; 11: 32–36.
  5. Botto LD, Moore CA, Khoury MJ, et al. Neural-tube defects. N Engl J Med. 1999; 341(20): 1509–1519.
  6. Canan S, Aktaş A, Ulkay MB, et al. Prenatal exposure to a non-steroidal anti-inflammatory drug or saline solution impairs sciatic nerve morphology: a stereological and histological study. Int J Dev Neurosci. 2008; 26(7): 733–738.
  7. Carp HJ, Fein A, Nebel L. Effect of diclofenac on implantation and embryonic development in the rat. Eur J Obstet Gynecol Reprod Biol. 1988; 28(3): 273–277.
  8. Chan LYS, Chiu PYu, Siu NSS, et al. Diclofenac-induced embryotoxicity is associated with increased embryonic 8-isoprostaglandin F2alpha level in rat whole embryo culture. Reprod Toxicol. 2002; 16(6): 841–844.
  9. Chan LY, Chiu PY, Siu SS, et al. A study of diclofenac-induced teratogenicity during organogenesis using a whole rat embryo culture model. Hum Reprod. 2001; 16(11): 2390–2393.
  10. Chen LC, Ashcroft DM. Do selective COX-2 inhibitors increase the risk of cerebrovascular events? A meta-analysis of randomized controlled trials. J Clin Pharm Ther. 2006; 31(6): 565–576.
  11. Davey PG. Overview of drug interactions with the quinolones. J Antimicrob Chemother. 1988; 22 Suppl C: 97–107.
  12. Dawood MY. Nonsteroidal antiinflammatory drugs and reproduction. Am J Obstet Gynecol. 1993; 169(5): 1255–1265.
  13. Drake VJ, Koprowski SL, Lough JW, et al. Gastrulating chick embryo as a model for evaluating teratogenicity: a comparison of three approaches. Birth Defects Res A Clin Mol Teratol. 2006; 76(1): 66–71.
  14. Fortun PJ, Hawkey CJ, Fortun PJ, et al. Nonsteroidal antiinflammatory drugs and the small intestine. Curr Opin Gastroenterol. 2005; 21(2): 169–175.
  15. Gardner WJ. Myelomeningocele, the result of rupture of the embryonic neural tube. Cleve Clin Q. 1960; 27: 88–100.
  16. Gevrek F, Kara M, Ragbetli M, et al. Effects of prenatally exposed diclofenac sodium on rat heart tissue:a stereological and histological study. Turk J Med Sci. 2015; 45: 474–480.
  17. Gokcimen A, Rağbetli MC, Baş O, et al. Effect of prenatal exposure to an anti-inflammatory drug on neuron number in cornu ammonis and dentate gyrus of the rat hippocampus: a stereological study. Brain Res. 2007; 1127(1): 185–192.
  18. Güney O, Canbilen A, Konak A, et al. The effects of folic acid in the prevention of neural tube development defects caused by phenytoin in early chick embryos. Spine (Phila Pa 1976). 2003; 28(5): 442–445.
  19. Güven D, Altunkaynak BZ, Ayranci E, et al. Stereological and histopathological evaluation of ovary and uterine horns of female rats prenatally exposed to diclofenac sodium. J Obstet Gynaecol. 2013; 33(3): 258–263.
  20. Hamburger V, Hamilton HL. A series of normal stages in the development of the chick embryo. J Morphol. 1951; 88(1): 49–92.
  21. Honein MA, Paulozzi LJ, Mathews TJ, et al. Impact of folic acid fortification of the US food supply on the occurrence of neural tube defects. JAMA. 2001; 285(23): 2981–2986.
  22. Kudo C, Kori M, Matsuzaki K, et al. Diclofenac inhibits proliferation and differentiation of neural stem cells. Biochem Pharmacol. 2003; 66(2): 289–295.
  23. Lee H, Nagele RG, Pietrolungo JF. Toxic and teratologic effects of caffeine on explanted early chick embryos. Teratology. 1982; 25(1): 19–25.
  24. Manning N, Archer N. Treatment and outcome of serious structural congenital heart disease. Semin Neonatol. 2001; 6(1): 37–47.
  25. Mete M, Gurcu B, Collu F, et al. Effects of lacosamide "a novel antiepileptic drug" in the early stages of chicken embryo development. Childs Nerv Syst. 2016; 32(9): 1715–1719.
  26. Mortimer EA. The puzzling epidemiology of neural tube defects. Pediatrics. 1980; 65(3): 636–638.
  27. Nielsen GL, Sørensen HT, Larsen H, et al. Risk of adverse birth outcome and miscarriage in pregnant users of non-steroidal anti-inflammatory drugs: population based observational study and case-control study. BMJ. 2001; 322(7281): 266–270.
  28. Olesen C, Steffensen FH, Nielsen GL, et al. Drug use in first pregnancy and lactation: a population-based survey among Danish women. The EUROMAP group. Eur J Clin Pharmacol. 1999; 55(2): 139–144.
  29. Ostensen M, Ramsey-Goldman R. Treatment of inflammatory rheumatic disorders in pregnancy: what are the safest treatment options? Drug Saf. 1998; 19(5): 389–410.
  30. Ostensen M. Nonsteroidal anti-inflammatory drugs during pregnancy. Scand J Rheumatol Suppl. 1998; 107: 128–132.
  31. Parman T, Chen G, Wells PG. Free radical intermediates of phenytoin and related teratogens. Prostaglandin H synthase-catalyzed bioactivation, electron paramagnetic resonance spectrometry, and photochemical product analysis. J Biol Chem. 1998; 273(39): 25079–25088.
  32. Ragbetli MC, Ozyurt B, Aslan H, et al. Effect of prenatal exposure to diclofenac sodium on Purkinje cell numbers in rat cerebellum: a stereological study. Brain Res. 2007; 1174: 130–135.
  33. Reddy NC, Anjaneyulu Y, Sivasankari B, et al. Comparative toxicity studies in birds using nimesulide and diclofenac sodium. Environ Toxicol Pharmacol. 2006; 22(2): 142–147.
  34. Rodier PM. Chronology of neuron development: animal studies and their clinical implications. Dev Med Child Neurol. 1980; 22(4): 525–545.
  35. Savaşer A, Ozkan Y, Işimer A. Preparation and in vitro evaluation of sustained release tablet formulations of diclofenac sodium. Farmaco. 2005; 60(2): 171–177.
  36. Segev S, Rehavi M, Rubinstein E. Quinolones, theophylline, and diclofenac interactions with the gamma-aminobutyric acid receptor. Antimicrob Agents Chemother. 1988; 32(11): 1624–1626.
  37. Siu SS, Yeung JH, Lau TK. A study on placental transfer of diclofenac in first trimester of human pregnancy. Hum Reprod. 2000; 15(11): 2423–2425.
  38. Tunçbilek E, Boduroğlu K, Alikaşifoğlu M. Neural tube defects in Turkey: prevalence, distribution and risk factors. Turk J Pediatr. 1999; 41(3): 299–305.
  39. Vatansever HS, Umur AS, Inan VS, et al. The effects of methotrexate on the development of neural tube defects in the chick embryo. Turk J Vet Anim Sci. 2003; 27: 1119–1125.
  40. Von Recklinghausen F. Untersuchungen über die Spina bifida. Arch Pathol Anat. 1886; 105: 243–373.
  41. Wallace JL, Del Soldato P. The therapeutic potential of NO-NSAIDs. Fundam Clin Pharmacol. 2003; 17(1): 11–20.
  42. Yakushiji T, Shirasaki T, Akaike N. Non-competitive inhibition of GABAA responses by a new class of quinolones and non-steroidal anti-inflammatories in dissociated frog sensory neurones. Br J Pharmacol. 1992; 105(1): 13–18.
  43. Yerby MS. Clinical care of pregnant women with epilepsy: neural tube defects and folic acid supplementation. Epilepsia. 2003; 44 Suppl 3: 33–40.
  44. Yurt KK, Kaplan S, Kıvrak EG. The neuroprotective effect of melatonin on the hippocampus exposed to diclofenac sodium during the prenatal period. J Chem Neuroanat. 2018; 87: 37–48.
  45. Zenker M, Klinge J, Krüger C, et al. Severe pulmonary hypertension in a neonate caused by premature closure of the ductus arteriosus following maternal treatment with diclofenac: a case report. J Perinat Med. 1998; 26(3): 231–234.

Regulations

Important: This website uses cookies. More >>

The cookies allow us to identify your computer and find out details about your last visit. They remembering whether you've visited the site before, so that you remain logged in - or to help us work out how many new website visitors we get each month. Most internet browsers accept cookies automatically, but you can change the settings of your browser to erase cookies or prevent automatic acceptance if you prefer.

By VM Media Group sp. z o.o., Grupa Via Medica, Świętokrzyska 73, 80–180 Gdańsk, Poland

tel.: +48 58 320 94 94, faks: +48 58 320 94 60, e-mail: viamedica@viamedica.pl