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Metabolomic perturbation precedes glycolytic dysfunction and procreates hyperglycemia in a rat model due to bisphenol S exposure.
Environmental Toxicology and Pharmacology ( IF 4.2 ) Pub Date : 2020-03-20 , DOI: 10.1016/j.etap.2020.103372
Kapil Mandrah 1 , Veena Jain 1 , Jamal Ahmad Ansari 2 , Somendu Kumar Roy 1
Affiliation  

Previous studies highlighted bisphenol S (BPS), an industrial chemical responsible for harmful effects comparable to its congener substance bisphenol A (BPA). Accounted for various adversities to biological functions, it could alter the expression of endogenous metabolites in many metabolic processes. The study was aimed to investigate the altered metabolites in hyperglycemic condition triggered by sub-chronic exposure of BPS in serum and urine samples of Wistar rats. Invaded effects of hyperglycemia due to BPS exposure on Wistar rats were investigated by oral glucose tolerance test (OGTT) and insulin tolerance test (ITT). Metabolomic profiling of serum and urinary metabolites was done by gas chromatography-mass spectrometry (GC–MS) analysis. The metabolomics data were represented by one way ANOVA, principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA) along with the mapping of perturbed metabolic pathways. The OGTT and ITT showed increased levels of glucose in treated animals with median and high doses, indicating the manifestation of hyperglycemia. The metabolomic profiling of serum and urine revealed BPS could cause consequential metabolomic perturbation mainly of amino acids, sugars, and organic acids. Furthermore, the extrapolation of Kyoto Encyclopedia of Genes and Genomes (KEGG) based systematic analysis helped to monitor the altered pathways, including amino acids, glycolysis, pyruvate metabolism, etc., which were provoked due to BPS exposure. The overview of the perturbed metabolite profiling in rats promisingly showed early diagnostic markers of hyperglycemic condition triggered due to the BPS exposure. Findings from this study will be helpful towards the exploration of mechanistic insights of several disturbed pathways.



中文翻译:

在大鼠模型中,由于双酚S暴露,代谢组学紊乱先于糖酵解功能障碍,并产生高血糖症。

先前的研究强调了双酚S(BPS),一种工业化学品,其危害性可与同类双酚A(BPA)媲美。考虑到生物功能的各种不利因素,它可能会改变许多代谢过程中内源性代谢物的表达。这项研究旨在研究Wistar大鼠血清和尿液样品中BPS的亚慢性暴露引起的高血糖状态下代谢物的变化。通过口服葡萄糖耐量试验(OGTT)和胰岛素耐量试验(ITT)研究了BPS暴露对Wistar大鼠引起的高血糖的入侵作用。血清和尿液代谢物的代谢组学分析通过气相色谱-质谱(GC-MS)分析完成。代谢组学数据通过一种方差分析,主成分分析(PCA),偏最小二乘判别分析(PLS-DA)以及干扰代谢途径的映射。OGTT和ITT在中剂量和高剂量治疗动物中显示出较高的葡萄糖水平,表明高血糖症的表现。血清和尿液的代谢组学分析表明,BPS可能引起随后的代谢组学扰动,主要是氨基酸,糖和有机酸。此外,基于《京都基因与基因组百科全书》(KEGG)的系统分析的推断有助于监测由于BPS暴露而引起的改变的途径,包括氨基酸,糖酵解,丙酮酸代谢等。对大鼠代谢物谱分析的概述有望显示出由于BPS暴露而触发的高血糖状况的早期诊断标记。

更新日期:2020-03-20
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