Effects of lacosamide “a novel antiepileptic drug” in the early stages of chicken embryo development

Mete, Mesut; Gürcü, Beyhan; Çöllü, Fatih; Ünsal, Ülkün Ünlü; Duransoy, Yusuf Kurtuluş; Tuğlu, Mehmet İbrahim; Selçukı, Mehmet

doi:10.1007/s00381-016-3181-4

Cited by 21 publications

(16 citation statements)

References 17 publications

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“…For example, congenital abnormalities such as growth retardation, microcephaly, orofacial defects, and NT damage are associated with AED treatment. Mete et al [6] investigated the effects of LCM on chicken embryo development and observed anencephaly with growth retardation during macroscopic examinations. The present study evaluated whether histological changes occurred at the NT level following LCM treatment and found that, although the NT closed, there were dosedependent increases in proliferating cells and pyknotic cells, and the cells were organized into a compact structure.…”

Section: Discussionmentioning

confidence: 99%

“…After 30 h of incubation, the eggs were opened under 4× optical magnification [7][8][9] at Hamburger-Hamilton stage 9 [8] and rinsed with 70% ethanol. Then, a piece of adhesive tape was placed close to the egg air cavity and a small window was opened for the injections [6].…”

Section: Methodsmentioning

confidence: 99%

“…Next, the embryos were randomly separated into a control group (Group 1; n = 7) and three LCM-treated groups (0.12 mg, sub-therapeutic group, n = 7; 0.5 mg, therapeutic group, n = 7, and 1.6 mg, supra-therapeutic group, n = 7). Within each group, the embryonic disks were identified and the same volume of liquid was injected under each disk with a 30-gauge syringe, as described previously by Mete et al [6]. Briefly, a solution of 12, 50, or 160 μL of LCM was diluted with physiological saline to a total volume of 180 μL.…”

Section: Methodsmentioning

confidence: 99%

“…The teratogenic effects of various AEDs, such as valproic acid, sodium phenytoin, and levetiracetam have been investigated but the effects of LCM, which is a novel third-generation AED that has recently been used frequently for the treatment of partial-onset seizures, remain unclear. Its possible side effects on fetal development have been investigated previously [6] but detailed studies of its influence on NT development have yet to be performed.…”

Section: Introductionmentioning

confidence: 99%

“…AEDs generally produce neurotoxic effects during reflex maturation and can lead to cell death. In studies on chickens, high-dose AEDs cause growth anomalies and a combination of AED enhances these effects [6,21].…”

mentioning

confidence: 99%

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The Effects of Lacosamide in the Early Stages of Neural Tube Development in Chick Embryos

Gürcü

Mete²,

Çöllü³

et al. 2018

Celal Bayar Üniversitesi Fen Bilimleri Dergisi

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Antiepileptic drugs (AED) are teratogens that confer a risk of various congenital malformations including neural tube defects. Lacosamide (LCM) is a novel third-generation AED and its effects on neural tube (NT) development remain unclear. Thus, the aim of the present study was to investigate the effects of LCM in the early stages of NT development in the chicken embryo. Three different doses of LCM were applied under the embryonic disks of chicken embryos after they were incubated for 30 hours. Incubation was continued for an additional 80 hours and then all embryos were obtained for routine histology. In the LCM-treated groups, there was occlusion in the middle and ventral levels of the cavity. In the group treated with 1.60 mg of LCM, the NT cavity was closed, the notochord exhibited deterioration, and cellular association appeared abnormal. In the groups treated with 0.12 and 0.5 mg of LCM, the ectoderm layer surrounding the embryo was hypertrophic and the number of pyknotic cells increased in a dose-dependent manner. Thus, different doses of LCM had different effects. The results of this study demonstrated that LCM causes histopathological alterations during the neurulation stage that might ultimately result in the development of congenital defects and/or malformations.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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The Effects of Lacosamide in the Early Stages of Neural Tube Development in Chick Embryos

Gürcü

Mete²,

Çöllü³

et al. 2018

Celal Bayar Üniversitesi Fen Bilimleri Dergisi

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Impact of Bisphenol A on neural tube development in 48‐hr chicken embryos

Atay

Ertekin

Bozkurt

et al. 2020

Birth Defects Research

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Objectives: Bisphenol A (BPA) is one of the most heavily produced chemicals in the world. BPA is involved in the production of many substances such as cosmetics, various foodstuffs, toys, personal care products, detergents and plastic bottles all that are frequently used in daily life. Depending on BPA exposure, sexual maturation and reproductive function, and bone and brain development are adversely affected. The aim of this study is to investigate the possible effects of BPA on the development of the nervous system and neural tube in 48-hr chicken embryos. Methods: Thirty specific pathogen-free (SPF) fertilized eggs were used in the study. SPF eggs were placed in the incubator and divided into three groups at 28 hr of incubation; control, BPA 1 and BPA 2 (10 eggs in each group). At this stage of incubation, two different doses of BPA were injected subblastodermically with the Hamilton microinjector. At the end of 48 hr of incubation, all eggs were opened and embryos were dissected and separated from the embryonic membrane. All embryos were evaluated morphologically and histopathologically. Results: As the BPA dose increased, delays in the development of the nervous system and midline closure increased in the early period of chicken embryos. Depending on the dose, it was found that the embryo's crown-rump length and somite number decreased (p < .05). Conclusion: It was determined that BPA application on early chicken embryos adversely affected neural tube development. It was also found to delay midline closure.

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The influence of different sugammadex doses on neural tube development in early‐stage chick embryos

Ayhan

Efe

Fidan

et al. 2023

Birth Defects Research

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BackgroundSugammadex is a modified gamma‐cyclodextrin that has been developed with the goal of reversing the steroidal neuromuscular blocking agents. The aim of the present study is to investigate the effects of different sugammadex doses on embryologic and neural tube development in an early‐stage chick embryo model.MethodsA total of 100 specific pathogen‐free, fertilized domestic chicken eggs were randomly divided into five groups (n = 20, each), and placed in an automatic cycle incubator. The eggs in the “control (C)” group were incubated without administration of any drug till the end of the experiment. Sub‐blastodermic administration of 0.9% NaCl as vehicle control (VC) and different doses of sugammadex solutions prepared with the latter [2 mg/mL (LD), 4 mg/mL (MD), 16 mg/mL (HD)] were performed at 30 hr of incubation. All embryos were removed from the eggs at 72 hr when they were expected to reach Hamburger‐Hamilton (HH) stages 19–20, then they were fixed, and evaluated histo‐morphologically.ResultsEmbryonic development was not observed in 11 eggs (1 in C, 1 in VC; 3 in LD, 3 in MD, and 3 in HD). All the developed embryos were compatible with the HH stages 19–20. A neural tube closure defect was detected in one embryo in the HD group. No statistically significant difference was found between the groups in terms of embryonic and neural tube developments.ConclusionsNo significant association was found between the drug and adverse outcomes; however, a trend with dosing was seen. Further studies are required before conclude on safety and extrapolate these results to human beings.

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Effects of lacosamide “a novel antiepileptic drug” in the early stages of chicken embryo development

Abstract: Based on our data, LCM may cause growth retardation or major congenital malformations. Nevertheless, more extensive investigations of its reliability are needed.

Cited by 21 publications

References 17 publications

The Effects of Lacosamide in the Early Stages of Neural Tube Development in Chick Embryos

The Effects of Lacosamide in the Early Stages of Neural Tube Development in Chick Embryos

Impact of Bisphenol A on neural tube development in 48‐hr chicken embryos

The influence of different sugammadex doses on neural tube development in early‐stage chick embryos

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