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硒和番茄红素通过抑制氧化应激、神经炎症和细胞凋亡改善甲基苯丙胺诱导的仔鼠神经毒性。

Selenium and Lycopene Ameliorate Methamphetamine-induced Neurotoxicity in Offspring Rats by Suppressing Oxidative Stress, Neuro-inflammation, and Apoptosis.

作者信息

Badiee Mahdieh Sadat, Salehcheh Maryam, Moosavi Mehrnoosh, Saburi Ehsan, Ebrahimzadeh-Bideskan Alireza, Fakhredini Fereshtesadat, Mahdavinia Masoud

机构信息

Student Research Committee, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

Department of Toxicology, Faculty of Pharmacy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

出版信息

Biol Trace Elem Res. 2025 Aug 23. doi: 10.1007/s12011-025-04685-z.

Abstract

Methamphetamine (METH) is an illicit drug and sympathetic nervous system stimulant that easily crosses the placenta due to its low molecular weight and high lipid solubility, thus affecting the pregnant mother and fetus. Considering the antioxidant and anti-inflammatory properties of selenium (Se) and lycopene (LYCO), as well as their ability to cross the blood-brain barrier and placental and be secreted into milk, this study aimed to evaluate the combined effects of Se and LYCO on METH-induced neurotoxicity in offspring rats. Thirty pregnant rats were divided into seven groups (n = 3-6), including control, METH (5 mg/kg, ip), METH and Se (2.5 mg/kg, gavage), METH and LYCO (10 mg/kg, gavage), METH in combination of Se with LYCO, Se, and LYCO. METH (3 consecutive days a week), Se (every other day), and LYCO (once daily) were administered for 42 days during pregnancy and breastfeeding. After the end of the study, antioxidant, oxidant, pro-inflammatory, and apoptosis factors were measured. Histological and immunofluorescence examinations with markers glial fibrillary acidic protein (GFAP) and vimentin were performed. Treatment with Se and LYCO reduced the levels of interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), reactive oxygen species (ROS), thiobarbituric acid-reactive substances (TBARS), and the expression of nuclear factor kappa B (NF-κB), Bcl-2-associated x protein (Bax), GFAP, and vimentin proteins and increased the level of total thiol, catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and the expression of B-cell lymphoma-2 (Bcl-2) protein compared to the METH group. Treatment with Se and LYCO could modulate METH-induced neurotoxicity in offspring rats by suppressing oxidative stress, neuroinflammation, apoptosis, and the expression of NF-κB, GFAP, and vimentin proteins.

摘要

甲基苯丙胺(METH)是一种非法药物和交感神经系统兴奋剂,因其分子量低、脂溶性高,很容易穿过胎盘,从而影响怀孕的母亲和胎儿。鉴于硒(Se)和番茄红素(LYCO)具有抗氧化和抗炎特性,以及它们能够穿过血脑屏障、胎盘并分泌到乳汁中,本研究旨在评估Se和LYCO对METH诱导的仔鼠神经毒性的联合作用。将30只怀孕大鼠分为七组(n = 3 - 6),包括对照组、METH组(5 mg/kg,腹腔注射)、METH + Se组(2.5 mg/kg,灌胃)、METH + LYCO组(10 mg/kg,灌胃)、METH + Se + LYCO组、Se组和LYCO组。在怀孕和哺乳期间,每周连续3天给予METH,每隔一天给予Se,每天给予LYCO,持续42天。研究结束后,检测抗氧化、氧化、促炎和凋亡因子。用胶质纤维酸性蛋白(GFAP)和波形蛋白标记物进行组织学和免疫荧光检查。与METH组相比,Se和LYCO治疗降低了白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、活性氧(ROS)、硫代巴比妥酸反应性物质(TBARS)的水平,以及核因子κB(NF-κB)、Bcl-2相关X蛋白(Bax)、GFAP和波形蛋白的表达,增加了总巯基、过氧化氢酶(CAT)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GPx)的水平以及B细胞淋巴瘤-2(Bcl-2)的表达。Se和LYCO治疗可通过抑制氧化应激、神经炎症、细胞凋亡以及NF-κB、GFAP和波形蛋白的表达来调节METH诱导的仔鼠神经毒性。

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