Effect of antiseizure drugs on growing bone in prepubertal non-epileptic rats

IF 3.5 3区医学 Q2 FOOD SCIENCE & TECHNOLOGY

Food and Chemical Toxicology Pub Date : 2025-07-30 DOI:10.1016/j.fct.2025.115671

Beril Dilber , Seren Gülşen Gürgen , Uğur Yazar , Hayrunnisa Yeşil Sarsmaz , Gülnur Esenülkü , Pınar Özkan Kart , Nihal Yıldız , Ali Samet Topsakal , Ali Cansu

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引用次数: 0

Abstract

To investigate the histologic effects of topiramate (TPM), lamotrigine (LTG), levetiracetam (LEV), lacosamide (LCM), clobazam (CLB), and zonisamide (ZNS) on rat bone. Seventy male Wistar-Albino rats (aged 21–24 days) were divided into 7 experimental groups with 10 rats each:(i) Control group, (ii) TPM group (40 mg/kg/day), (iii) LTG group (10 mg/kg/day), (iv) LEV group (200 mg/kg/day), (v) LCM group (30 mg/kg/day), (vi) CLB group (50 mg/kg/day), and (vii) ZNS group (100 mg/kg/day). All the drugs were administered by gavage for 90 days.The specimens were analyzed using apoptosis (TUNEL) and immunohistochemical staining. The number of osteoblasts and the thickness of femoral compact bone decreased significantly in TPM, LTG, LEV, LCM, CLB, and ZNS groups. The number of TUNEL-positive cells was higher in all experimental groups compared to the control group, and this difference was statistically significant in CLB and ZNS groups (p < 0.001 for both). The HSCORE increased significantly for caspase-3, caspase-9, and Bcl-2-associated X protein (BAX) immunohistochemical staining (p < 0.001) and increased significantly in TPM, LTG, LEV, LCM, CLB, and ZNS groups (p < 0.001). In summary, the use of antiseizure medications adversely affected the expression of proteins critical to bone physiology in young non-epileptic rats, with varying degrees of impact.

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抗癫痫药物对青春期前非癫痫大鼠骨生长的影响。

目的探讨托吡酯（TPM）、拉莫三嗪（LTG）、左乙拉西坦（LEV）、拉科沙胺（LCM）、氯巴赞（CLB）和唑尼沙胺（ZNS）对大鼠骨的组织学影响。选取21 ~ 24日龄雄性Wistar-Albino大鼠70只，分为7个实验组，每组10只：(i)对照组，（ii） TPM组（40 mg/kg/d），（iii） LTG组（10 mg/kg/d），（iv） LEV组（200 mg/kg/d）， (v) LCM组（30 mg/kg/d），（vi） CLB组（50 mg/kg/d），（vii） ZNS组（100 mg/kg/d）。所有药物均灌胃给药90 d。采用细胞凋亡（TUNEL）和免疫组化染色对标本进行分析。TPM、LTG、LEV、LCM、CLB和ZNS组成骨细胞数量和股骨致密骨厚度均显著降低。各实验组tunel阳性细胞数均高于对照组，CLB组和ZNS组差异有统计学意义(p

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来源期刊

Food and Chemical Toxicology 工程技术-毒理学

CiteScore

10.90

自引率

4.70%

发文量

651

审稿时长

31 days

期刊介绍： Food and Chemical Toxicology (FCT), an internationally renowned journal, that publishes original research articles and reviews on toxic effects, in animals and humans, of natural or synthetic chemicals occurring in the human environment with particular emphasis on food, drugs, and chemicals, including agricultural and industrial safety, and consumer product safety. Areas such as safety evaluation of novel foods and ingredients, biotechnologically-derived products, and nanomaterials are included in the scope of the journal. FCT also encourages submission of papers on inter-relationships between nutrition and toxicology and on in vitro techniques, particularly those fostering the 3 Rs. The principal aim of the journal is to publish high impact, scholarly work and to serve as a multidisciplinary forum for research in toxicology. Papers submitted will be judged on the basis of scientific originality and contribution to the field, quality and subject matter. Studies should address at least one of the following: -Adverse physiological/biochemical, or pathological changes induced by specific defined substances -New techniques for assessing potential toxicity, including molecular biology -Mechanisms underlying toxic phenomena -Toxicological examinations of specific chemicals or consumer products, both those showing adverse effects and those demonstrating safety, that meet current standards of scientific acceptability. Authors must clearly and briefly identify what novel toxic effect (s) or toxic mechanism (s) of the chemical are being reported and what their significance is in the abstract. Furthermore, sufficient doses should be included in order to provide information on NOAEL/LOAEL values.