5-Methoxy-N-methyl-N-isopropyltryptamine (5-MeO-MiPT) is a novel psychoactive substance exhibiting a tryptamine structure. Despite its increasing prevalence, the environmental impact of 5-MeO-MiPT remains unexplored. Our prior investigation revealed that 5-MeO-MiPT induced inhibited spontaneous movement and prompted anxiety-like behavior in adult zebrafish-a validated toxicological model. To elucidate this phenomenon and establish a correlation between metabolomics and behavioral changes induced by 5-MeO-MiPT, zebrafish were administered varying drug concentrations. Zebrafishes were subjected to injections of different 5-MeO-MiPT concentrations. Subsequent metabolomic analysis of endogenous metabolites affected by the drug unveiled substantial variations in metabolic levels between the control group and the drug-injected cohorts. A total of 22 distinct metabolites emerged as potential biomarkers. Further scrutiny identified seven pathways significantly influenced by 5-MeO-MiPT. A focused exploration into amino acid metabolism, lipid metabolism, and energy metabolism unveiled that the metabolic repercussions of 5-MeO-MiPT on zebrafish resulted in observable brain damage. Notably, the study identified a consequential disruption in the liver-brain pathway. The comprehensive metabolomic approach employed herein effectively discerned the impact of 5-MeO-MiPT on zebrafish metabolism. This approach also shed light on the mechanism underpinning the anxiety-like behavior observed in zebrafish post-drug injection. Specifically, our findings indicate that 5-MeO-MiPT induces brain damage, particularly within the liver-brain pathway.

中文翻译：

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对 5-MeO-MiPT 对斑马鱼（斑马鱼）行为影响的非靶向代谢组学见解


5-甲氧基-N-甲基-N-异丙基色胺（5-MeO-MiPT）是一种具有色胺结构的新型精神活性物质。尽管 5-MeO-MiPT 的流行率不断上升，但其对环境的影响仍未得到探索。我们之前的研究表明，5-MeO-MiPT 会诱导成年斑马鱼抑制自发运动并引发焦虑样行为，这是一种经过验证的毒理学模型。为了阐明这一现象并建立代谢组学与 5-MeO-MiPT 诱导的行为变化之间的相关性，对斑马鱼施用不同浓度的药物。斑马鱼接受了不同浓度的 5-MeO-MiPT 注射。随后对受药物影响的内源代谢物进行的代谢组学分析揭示了对照组和注射药物组之间代谢水平的显着差异。共有 22 种不同的代谢物成为潜在的生物标志物。进一步的审查发现了 7 个受 5-MeO-MiPT 显着影响的途径。对氨基酸代谢、脂质代谢和能量代谢的集中探索表明，5-MeO-MiPT 对斑马鱼的代谢影响导致了可观察到的脑损伤。值得注意的是，该研究发现了肝脑通路的相应破坏。本文采用的综合代谢组学方法有效地识别了 5-MeO-MiPT 对斑马鱼代谢的影响。这种方法还揭示了斑马鱼注射药物后观察到的焦虑样行为的机制。具体来说，我们的研究结果表明 5-MeO-MiPT 会引起脑损伤，特别是在肝脑通路内。