辛伐他汀对片足动物沙鼠代谢的直接和跨代影响

IF 4.1 2区环境科学与生态学 Q1 MARINE & FRESHWATER BIOLOGY

Aquatic Toxicology Pub Date : 2025-02-01 DOI:10.1016/j.aquatox.2024.107221

João A. Rodrigues , Raquel S. Chaves , Miguel M. Santos , Teresa Neuparth , Ana M. Gil

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引用次数: 0

摘要

在这项研究中，据我们所知，首次应用非靶向核磁共振（NMR）代谢组学来评估片脚类动物Gammarus locusta直接和跨代（分别为F0和F3代）暴露于辛伐他汀（SIM）的代谢影响，辛伐他汀是一种广泛用于治疗高胆固醇血症的药物。结果揭示了这些影响的重要的性别依赖性质。直接暴露的雄性表现出增强的葡萄糖分解代谢和三羧酸（TCA）循环活性，同时适应渗透调节和乙醛酸代谢。暴露的雌性只表现出很小的渗透调节作用。这表明，雄性暴露的反应可能反映了报告的高水平的法尼酸甲酯激素（雌性低水平）和顶端因素的改变，即生长下降。相反，跨代效应仅在雌性中被发现，影响能量代谢（糖酵解和TCA循环增强）和渗透调节反应。这表达了雌性配子传递直接暴露于SIM的影响的能力。据推测，这种影响与报道的延迟成熟和转录组偏差有关，影响碳水化合物和脂质代谢，可能特别涉及多巴胺和胆碱代谢中的苯丙氨酸/酪氨酸和胆碱。

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Direct and transgenerational effects of simvastatin on the metabolism of the amphipod Gammarus locusta

In this study, untargeted Nuclear Magnetic Resonance (NMR) metabolomics was applied for the first time, to our knowledge, to assess the metabolic impact of direct and transgenerational exposure (F0 and F3 generations, respectively) of amphipods Gammarus locusta to simvastatin (SIM), a pharmaceutical widely prescribed for the treatment of hypercholesterolemia. Results revealed the important gender-dependent nature of each of these effects. Directly exposed males showed enhanced glucose catabolism and tricarboxylic acid (TCA) cycle activity, in tandem with adaptations in osmotic regulation and glyoxylate metabolism. Exposed females exhibited only a small osmoregulatory effect. It is suggested that the response of exposed males may reflect reported high levels of methyl farnesoate hormone (low levels in females) and alterations in apical factors, namely decreased growth. Conversely, transgenerational effects were identified only in females, with impact on energy metabolism (glycolysis and TCA cycle enhancement) and osmoregulatory response. This expresses the ability of female gametes to transmit the effects of direct SIM exposure. Such effects were putatively related to reported delayed maturation and transcriptomic deviations impacting on carbohydrate and lipid metabolisms, possibly specifically engaging phenylalanine/tyrosine and choline in dopamine and choline metabolisms.

These findings reflect the importance of untargeted metabolomics in addressing not only direct exposure of contaminants, but also their transgenerational effects, potentially contributing towards improving hazard and risk assessment of biologically active compounds.

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来源期刊

Aquatic Toxicology 环境科学-毒理学

CiteScore

7.10

自引率

4.40%

发文量

250

审稿时长

56 days

期刊介绍： Aquatic Toxicology publishes significant contributions that increase the understanding of the impact of harmful substances (including natural and synthetic chemicals) on aquatic organisms and ecosystems. Aquatic Toxicology considers both laboratory and field studies with a focus on marine/ freshwater environments. We strive to attract high quality original scientific papers, critical reviews and expert opinion papers in the following areas: Effects of harmful substances on molecular, cellular, sub-organismal, organismal, population, community, and ecosystem level; Toxic Mechanisms; Genetic disturbances, transgenerational effects, behavioral and adaptive responses; Impacts of harmful substances on structure, function of and services provided by aquatic ecosystems; Mixture toxicity assessment; Statistical approaches to predict exposure to and hazards of contaminants The journal also considers manuscripts in other areas, such as the development of innovative concepts, approaches, and methodologies, which promote the wider application of toxicological datasets to the protection of aquatic environments and inform ecological risk assessments and decision making by relevant authorities.