被动给药氟西汀可进入 FSL 大鼠的幼年大脑并降低抗氧化防御能力,但不会改变血清素的周转。

IF 2.8 3区 医学 Q2 PHARMACOLOGY & PHARMACY
Stephan F Steyn, Malie Rheeders, Francois P Viljoen, Linda Brand
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引用次数: 0

摘要

背景:母乳中含有氟西汀,但目前还不清楚氟西汀或其活性代谢物诺氟西汀进入婴儿大脑的程度,也不清楚这种接触对神经生物学过程的影响。因此,我们旨在量化被动施用的氟西汀和去氟西汀在暴露的弗林德斯敏感品系(FSL)后代整个大脑中的浓度,并确定它们对血清素能功能和氧化还原状态的影响:成年弗林德斯敏感品系母鼠从产后第 04 天开始接受氟西汀(10 毫克/千克/天)或安慰剂治疗,为期 14 天。后代被动接受氟西汀治疗至出生后第18天,并于出生后第22天安乐死。通过液相色谱-质谱分析法(LC-MS)测量了全脑氟西汀、诺氟西汀、血清素(5-HT)、5-羟基吲哚乙酸(5-HIAA)、还原型谷胱甘肽(GSH)和氧化型谷胱甘肽(GSSG)的浓度:结果:不同菌株的全脑血清素和 5-羟基吲哚乙酸浓度以及血清素周转率(5-HIAA/5-HT)相当。与FRL对照组相比,未经治疗的FSL大鼠全脑GSH浓度较低,GSSG浓度较高,GSH/GSSG比率总体下降。被动给药氟西汀导致全脑浓度检测不到,而非氟西汀的平均浓度为 41.28 ± 6.47 纳克/克。FSL大鼠的血清素周转不受被动给药氟西汀的影响,而氧化还原状态(GSH/GSSG)却有所下降:我们的研究结果证实,被动给药氟西汀以去氟西汀的形式进入婴儿大脑,可能会影响氧化应激的调节过程。然而,还需要对长期的生物行为效应进行进一步的研究,以便有效地告知母乳喂养的母亲使用抗抑郁药的安全性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Passively administered fluoxetine reaches the juvenile brain of FSL rats and reduces antioxidant defences, without altering serotonin turnover.

Background: Fluoxetine is present in breast milk, yet it is unclear to what extent it, or its active metabolite, norfluoxetine, reaches the brain of the infant and what the effects of such exposure on neurobiological processes are. We therefore aimed to quantify the concentration of passively administered fluoxetine and norfluoxetine in the whole brains of exposed Flinders sensitive line (FSL) offspring and establish their influence on serotonergic function and redox status.

Methods: Adult FSL dams received fluoxetine (10 mg/kg/day), or placebo for fourteen days, beginning on postpartum day 04. Offspring were passively exposed to fluoxetine until postnatal day 18 and euthanized on postnatal day 22. Whole brain fluoxetine, norfluoxetine, serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), and reduced (GSH) and oxidized glutathione (GSSG) concentrations were measured via liquid chromatography-mass spectrometry (LC-MS) analysis.

Results: Whole-brain serotonin and 5-hydroxyindoleacetic acid concentrations, and serotonin turnover (5-HIAA/5-HT) were comparable between strains. Treatment-naïve FSL rats had lower GSH and higher GSSG whole-brain concentrations, relative to FRL controls, and an overall decreased GSH/GSSG ratio. Passively administered fluoxetine resulted in undetectable whole-brain concentrations, while norfluoxetine averaged 41.28 ± 6.47 ng/g. Serotonin turnover of FSL rats was unaffected by passively administered fluoxetine, while redox status (GSH/GSSG) was decreased.

Conclusion: Our findings confirm that passively administered fluoxetine reaches the infant brain in the form of norfluoxetine and may manipulate processes of oxidative stress regulation. Further studies into the long-term bio-behavioural effects are however needed to effectively inform breast feeding mothers on the safety of antidepressant-use.

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来源期刊
BMC Pharmacology & Toxicology
BMC Pharmacology & Toxicology PHARMACOLOGY & PHARMACYTOXICOLOGY&nb-TOXICOLOGY
CiteScore
4.80
自引率
0.00%
发文量
87
审稿时长
12 weeks
期刊介绍: BMC Pharmacology and Toxicology is an open access, peer-reviewed journal that considers articles on all aspects of chemically defined therapeutic and toxic agents. The journal welcomes submissions from all fields of experimental and clinical pharmacology including clinical trials and toxicology.
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