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An insight into the metabolic responses of ultra-small superparamagnetic particles of iron oxide using metabonomic analysis of biofluids

机译：使用生物流体的代谢组学分析洞察超小超顺磁性氧化铁颗粒的代谢反应

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Ultra-small superparamagnetic particles of iron oxides (USPIO) have been developed as intravenous organ/tissue-targeted contrast agents to improve magnetic resonance imaging (MRI) in vivo. However, their potential toxicity and effects on metabolism have attracted particular attention. In the present study, uncoated and dextran-coated USPIO were investigated by analyzing both rat urine and plasma metabonomes using high-resolution NMR-based metabonomic analysis in combination with multivariate statistical analysis. The wealth of information gathered on the metabolic profiles from rat urine and plasma has revealed subtle metabolic changes in response to USPIO administration. The metabolic changes include the elevation of urinary α-hydroxy-n-valerate, o- and p-HPA, PAG, nicotinate and hippurate accompanied by decreases in the levels of urinary α-ketoglutarate, succinate, citrate, N-methylnicotinamide, NAG DMA, allantoin and acetate following USPIO administration. The changes associated with USPIO administration included a gradual increase in plasma glucose, N-acetyl glycoprotein, saturated fatty acid, citrate, succinate, acetate, GPC, ketone bodies (β-hydroxybutyrate, acetone and acetoacetate) and individual amino acids, such as phenylalanine, lysine, isoleucine, glycine, glutamine and glutamate and a gradual decrease of myo-inositol, unsaturated fatty acid and triacylglycerol. Hence USPIO administration effects are reflected in changes in a number of metabolic pathways including energy, lipid, glucose and amino acid metabolism. The size- and surface chemistry-dependent metabolic responses and possible toxicity were observed using NMR analysis of biofluids. These changes may be attributed to the disturbances of hepatic, renal and cardiac functions following USPIO administrations. The potential biotoxicity can be derived from metabonomic analysis and serum biochemistry analysis. Metabonomic strategy offers a promising approach for the detection of subtle physiological responses on mammalian metabolism, and can be employed to investigate the potential adverse effects of other nanoparticles and nanomaterials on the environment and human health.
机译：已经开发出超小超顺磁性氧化铁颗粒（USPIO）作为静脉内靶向器官/组织的造影剂，以改善体内磁共振成像（MRI）。然而，它们潜在的毒性和对代谢的影响已引起特别关注。在本研究中，通过使用高分辨率基于NMR的代谢组学分析与多变量统计分析相结合的方法分析大鼠尿液和血浆代谢组，研究了未包衣和右旋糖酐包衣的USPIO。从大鼠尿液和血浆中代谢谱收集的大量信息表明，响应于USPIO给药，微妙的代谢变化。代谢变化包括尿中α-羟基-正戊酸，o-和p-HPA，PAG，烟酸和马尿酸升高，同时尿中α-酮戊二酸，琥珀酸，柠檬酸，N-甲基烟酰胺，NAG DMA水平降低，USPIO管理后的尿囊素和醋酸盐。与USPIO给药有关的变化包括血浆葡萄糖，N-乙酰基糖蛋白，饱和脂肪酸，柠檬酸盐，琥珀酸盐，乙酸盐，GPC，酮体（β-羟基丁酸盐，丙酮和乙酰乙酸盐）和个别氨基酸（例如苯丙氨酸）的逐渐增加，赖氨酸，异亮氨酸，甘氨酸，谷氨酰胺和谷氨酸盐，肌醇，不饱和脂肪酸和三酰基甘油逐渐减少。因此，USPIO的给药效果反映在许多代谢途径的变化中，包括能量，脂质，葡萄糖和氨基酸代谢。使用生物流体的NMR分析观察到大小和表面化学依赖性的代谢反应以及可能的毒性。这些变化可能归因于USPIO给药后肝，肾和心脏功能的紊乱。潜在的生物毒性可从代谢组学分析和血清生化分析得出。代谢组学策略为检测对哺乳动物新陈代谢的微妙生理反应提供了一种有前途的方法，可用于研究其他纳米颗粒和纳米材料对环境和人类健康的潜在不利影响。

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