Abstract
Nonylphenol (NP) was quantified using liquid chromatography tandem mass spectrometry (LC-MS/MS) in the urine and plasma of rats treated with 0, 50, and 250 mg/kg/day of NP for four consecutive days. A urinary metabolomic strategy was originally implemented by high performance liquid chromatography time of flight mass spectrometry (HPLC-QTOF-MS) to explore the toxicological effects of NP and determine the overall alterations in the metabolite profiles so as to find potential biomarkers. It is essential to point out that from the observation, the metabolic data were clearly clustered and separated for the three groups. To further identify differentiated metabolites, multivariate analysis, including principal component analysis (PCA), orthogonal partial least-squares discriminant analysis (OPLS-DA), high-resolution MS/MS analysis, as well as searches of Metlin and Massbank databases, were conducted on a series of metabolites between the control and dose groups. Finally, five metabolites, including glycine, glycerophosphocholine, 5-hydroxytryptamine, malonaldehyde (showing an upward trend), and tryptophan (showing a downward trend), were identified as the potential urinary biomarkers of NP-induced toxicity. In order to validate the reliability of these potential biomarkers, an independent validation was performed by using the multiple reaction monitoring (MRM)-based targeted approach. The oxidative stress reflected by urinary 8-oxo-deoxyguanosine (8-oxodG) levels was elevated in individuals highly exposed to NP, supporting the hypothesis that mitochondrial dysfunction was a result of xenoestrogen accumulation. This study reveals a promising approach to find biomarkers to assist researchers in monitoring NP.
Highlights
Nonylphenol (NP) is an artificial environmental pollutant produced from alkylphenols and a scientifically well-known xenoestrogen and endocrine disruptor [1]
When the rats in the control group were exposed to the NP-free condition, no NP was detected in the serum
NP was maintained at a certain concentration in blood for a period, and allowed to migrate to and accumulate in tissues, requiring subsequent experiments focusing on the study of NP-triggered variations of endogenous metabolites in the organisms
Summary
Nonylphenol (NP) is an artificial environmental pollutant produced from alkylphenols and a scientifically well-known xenoestrogen and endocrine disruptor [1]. NP is ubiquitous in the environment, such as in the wastewater, drinking water, rivers, and animals. As important sources of NP, alkylphenol polyethoxylates (APEOs) are used all over the world and in only a few Asian countries [2,3,4]. According to a study in Taiwan, NP in the milk of women who often have fish oil is abundant, reaching a concentration of 4.47 μg/kg [5,6]. In a recent study of 62 drinking water samples. Res. Public Health 2016, 13, 501; doi:10.3390/ijerph13050501 www.mdpi.com/journal/ijerph
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