Identification of potential biomarkers in cholestasis and the therapeutic effect of melatonin by metabolomics, multivariate data and pathway analyses

Yu,Han; Li,Yunzhou; Xu,Zongying; Wang,Dingnan; Shi,Shaohua; Deng,Huifang; Zeng,Baihui; Zheng,Zhili; Sun,Lili; Deng,Xiulan; Zhong,Xianggen

doi:10.3892/ijmm.2018.3859

Identification of potential biomarkers in cholestasis and the therapeutic effect of melatonin by metabolomics, multivariate data and pathway analyses

Authors:
- Han Yu
- Yunzhou Li
- Zongying Xu
- Dingnan Wang
- Shaohua Shi
- Huifang Deng
- Baihui Zeng
- Zhili Zheng
- Lili Sun
- Xiulan Deng
- Xianggen Zhong
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Affiliations: Synopsis of Golden Chamber, Chinese Medicine College, Beijing University of Chinese Medicine, Chaoyang, Beijing 100029, P.R. China, Pharmacology Departments, Chinese Medicine College, Beijing University of Chinese Medicine, Chaoyang, Beijing 100029, P.R. China
Published online on: September 5, 2018 https://doi.org/10.3892/ijmm.2018.3859
Pages: 2515-2526
Copyright: © Yu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The present study investigated the anti‑cholestatic effect of melatonin (MT) against α‑naphthyl isothiocyanate (ANIT)‑induced liver injury in rats and screened for potential biomarkers of cholestasis. Rats were administered ANIT by intraperitoneal injection and then sacrificed 36 h later. Serum biochemical parameters were measured and liver tissue samples were subjected to histological analysis. Active components in the serum were identified by gas chromatography‑mass spectrometry, while biomarkers and biochemical pathways were identified by multivariate data analysis. The results revealed that the serum levels of alanine aminotransferase, aspartate aminotransferase, total bilirubin, direct bilirubin, γ‑glutamyl transpeptidase, and alkaline phosphatase were reduced in rats with ANIT‑induced cholestasis that were treated with MT. The histological observations indicated that MT had a protective effect against ANIT‑induced hepatic tissue damage. Metabolomics analysis revealed that this effect was likely to be associated with the regulation of compounds related to MT synthesis and catabolism, and amino acid metabolism, including 5‑aminopentanoate, 5‑methoxytryptamine, L‑tryptophan, threonine, glutathione, L‑methionine, and indolelactate. In addition, principal component analysis demonstrated that the levels of these metabolites differed significantly between the MT and control groups, providing further evidence that they may be responsible for the effects induced by MT. These results provide an insight into the mechanisms underlying cholestasis development and highlight potential biomarkers for disease diagnosis.

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