Perinatal nicotine-induced neurotoxicity and behavioral alterations in newborn mice are associated with oxidative stress, inflammation and downregulated Nrf2/HO-1 signaling: protective role of Anethum graveolens.

IF 2.2 4区 生物学 Q3 CELL BIOLOGY
Saleh Maodaa, Jamaan S Ajarem, Reem S Alruhaimi, Ahmed A Allam, Naif G Altoom, Ayman M Mahmoud
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引用次数: 0

Abstract

Perinatal exposure to nicotine has been implicated in causing significant oxidative stress and long-term neurobehavioral abnormalities. This study explores, for the first time, the efficacy of Anethum graveolens (dill) extract in mitigating neurotoxicity, oxidative damage, inflammation, and behavioral disturbances in neonatal mice exposed to nicotine during the perinatal period. Pregnant mice were administered 50 mg/kg of A. graveolens extract orally from gestational day 1 (GD1) to postnatal day 15 (PD15), alongside subcutaneous injections of nicotine (0.25 mg/kg) from GD12 to PD15. Nicotine-exposed neonates exhibited delayed developmental milestones (eye opening and hair growth), impaired neuromotor functions (righting, rotating, and cliff avoidance reflexes), and heightened anxiety-like behaviors. Nicotine induced substantial tissue damage, elevated levels of reactive oxygen species (ROS), malondialdehyde (MDA), and pro-inflammatory cytokines, and suppressed glutathione (GSH) levels and antioxidant enzyme activities across different brain regions (cerebrum, cerebellum, and medulla oblongata). A. graveolens extract improved developmental markers, restored neuromotor functions, reduced anxiety-like behaviors, and attenuated oxidative stress and inflammation. Moreover, it enhanced antioxidant defenses and upregulated the expression of Nrf2 and heme oxygenase-1 (HO-1). These findings indicate that A. graveolens exerts a protective role against nicotine-induced neurotoxicity by modulating oxidative and inflammatory responses and attenuating neurobehavioral alterations.

围产期尼古丁诱导的新生小鼠神经毒性和行为改变与氧化应激、炎症和Nrf2/HO-1信号下调有关:茴香的保护作用
围产期暴露于尼古丁与引起显著的氧化应激和长期神经行为异常有关。本研究首次探讨了莳萝提取物在围产期暴露于尼古丁的新生小鼠中减轻神经毒性、氧化损伤、炎症和行为障碍的功效。妊娠小鼠从妊娠第1天(GD1)至产后第15天(PD15)口服50 mg/kg的石蜡提取物,同时从妊娠第12天至产后第15天皮下注射尼古丁(0.25 mg/kg)。尼古丁暴露的新生儿表现出发育里程碑延迟(睁眼和毛发生长),神经运动功能受损(翻正、旋转和悬崖回避反射),以及焦虑样行为加剧。尼古丁诱导了大量的组织损伤,活性氧(ROS)、丙二醛(MDA)和促炎细胞因子水平升高,并抑制了不同脑区(大脑、小脑和延髓)谷胱甘肽(GSH)水平和抗氧化酶活性。荆芥提取物改善发育指标,恢复神经运动功能,减少焦虑样行为,减轻氧化应激和炎症。增强抗氧化防御能力,上调Nrf2和血红素加氧酶-1 (HO-1)的表达。这些发现表明,荆芥通过调节氧化和炎症反应以及减轻神经行为改变,对尼古丁诱导的神经毒性具有保护作用。
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来源期刊
Journal of Molecular Histology
Journal of Molecular Histology 生物-细胞生物学
CiteScore
5.90
自引率
0.00%
发文量
68
审稿时长
1 months
期刊介绍: The Journal of Molecular Histology publishes results of original research on the localization and expression of molecules in animal cells, tissues and organs. Coverage includes studies describing novel cellular or ultrastructural distributions of molecules which provide insight into biochemical or physiological function, development, histologic structure and disease processes. Major research themes of particular interest include: - Cell-Cell and Cell-Matrix Interactions; - Connective Tissues; - Development and Disease; - Neuroscience. Please note that the Journal of Molecular Histology does not consider manuscripts dealing with the application of immunological or other probes on non-standard laboratory animal models unless the results are clearly of significant and general biological importance. The Journal of Molecular Histology publishes full-length original research papers, review articles, short communications and letters to the editors. All manuscripts are typically reviewed by two independent referees. The Journal of Molecular Histology is a continuation of The Histochemical Journal.
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