Acute administration of ibuprofen increases serum concentration of the neuroprotective kynurenine pathway metabolite, kynurenic acid: a pilot randomized, placebo-controlled, crossover study.
Acute administration of ibuprofen increases serum concentration of the neuroprotective kynurenine pathway metabolite, kynurenic acid: a pilot randomized, placebo-controlled, crossover study.
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DOI：
10.1007/s00213-022-06263-w
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发表时间：
2022-12
影响因子：
3.4
通讯作者：
Paulus, Martin P.
中科院分区：
文献类型：
--
作者：
Savitz, Jonathan;Ford, Bart N.;Kuplicki, Rayus;Khalsa, Sahib;Teague, T. Kent;Paulus, Martin P.
关键词：
至少有六种不同类型的抗癫痫治疗已被证明可以增加神经保护性犬尿氨酸途径（KP）代谢物犬尿烯酸（KynA），或减少神经毒性KP代谢物喹啉酸（QA）。包括布洛芬在内的非甾体抗炎药（NSAID）在治疗抑郁症方面显示出一定的疗效，但尚未在人体中研究其对KP的影响。评价布洛芬对循环KP代谢物的影响。在一项随机、安慰剂对照、交叉研究中，20名健康成人（10名女性）以平衡顺序接受200 mg布洛芬、600 mg布洛芬或安慰剂单次口服给药（NCT 02507219）。在下午三点左右，布洛芬/安慰剂给药后5小时抽取血清样品。通过串联质谱法在访视前盲测KP代谢物。采用线性混合效应模型分析数据。主要结局为KynA/QA，次要结局为KynA。Bonferroni校正后，治疗对KynA/QA有显著影响。该效应是由600 mg剂量后KynA浓度的增加驱动的，而不是相对于安慰剂的200 mg剂量（Cohen d=1.71）。相比之下，200 mg（d=1.03）和600 mg（d=2.05）剂量的布洛芬相对于安慰剂降低色氨酸浓度。鉴于其KynA升高作用，布洛芬可能在抑郁症以及其他以KynA减少为特征的神经炎性疾病中具有神经保护作用。
At least six different types of anti-depressant treatments have been shown to either increase the neuroprotective kynurenine pathway (KP) metabolite, kynurenic acid (KynA), or decrease the neurotoxic KP metabolite, quinolinic acid (QA). Non-steroidal anti-inflammatory drugs (NSAIDs) including ibuprofen have shown some efficacy in the treatment of depression but their effects on the KP have not been studied in humans. To evaluate the effect of ibuprofen on circulating KP metabolites. In a randomized, placebo-controlled, cross-over study, 20 healthy adults (10 women) received a single oral dose of 200mg ibuprofen, 600mg ibuprofen or placebo in a counterbalanced order (NCT02507219). Serum samples were drawn in the mid-afternoon, 5 hours after ibuprofen/placebo administration. KP metabolites were measured blind to visit by tandem mass spectrometry. Data were analyzed with linear mixed effect models. The primary outcome was KynA/QA and the secondary outcome was KynA. After Bonferroni correction, there was a significant effect of treatment on KynA/QA. The effect was driven by an increase in KynA concentration after the 600mg dose but not the 200mg dose relative to placebo (Cohen’s d=1.71). In contrast, both the 200mg (d=1.03) and 600mg (d=2.05) doses of ibuprofen decreased tryptophan concentrations relative to placebo. Given its KynA-elevating effects, ibuprofen could have neuroprotective effects in the context of depression as well as other neuroinflammatory disorders that are characterized by a reduction in KynA.
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DOI：
10.1038/npp.2012.248
发表时间：
2013-04
期刊：
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
影响因子：
--
作者：
通讯作者：
--
影响因子：
3.3
作者：
Maciejak, P.;Szyndler, J.;Plaznik, A.
通讯作者：
Plaznik, A.
DOI：
10.1016/j.bbi.2021.05.023
发表时间：
2021-08
期刊：
Brain, behavior, and immunity
影响因子：
--
作者：
Cosgrove KT;Kuplicki R;Savitz J;Burrows K;Simmons WK;Khalsa SS;Teague TK;Aupperle RL;Paulus MP
通讯作者：
Paulus MP
影响因子：
4.7
作者：
DUNN, AJ;WELCH, J
通讯作者：
WELCH, J
影响因子：
9.9
作者：
Gao, Xiang;Chen, Honglei;Ascherio, Alberto
通讯作者：
Ascherio, Alberto