For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
8
views
42
references
 Top references
cited by
1
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      1,329
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      iTRAQ-based quantitative proteomics analysis of the hepatoprotective effect of melatonin on ANIT-induced cholestasis in rats

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          The therapeutic effects of melatonin on cholestatic liver injury have received widespread attention recently. The aim of the present study was to investigate the mechanisms of the anti-cholestatic effects of melatonin against α-naphthyl isothiocyanate (ANIT)-induced liver injury in rats and to screen for potential biomarkers of cholestasis through isobaric tags for relative and absolute quantitation (iTRAQ) proteomics. Rats orally received melatonin (100 mg/kg body weight) or an equivalent volume of 0.25% carboxymethyl cellulose sodium salt 12 h after intraperitoneal injection of ANIT (75 mg/kg) and were subsequently sacrificed at 36 h after injection. Liver biochemical indices were determined and liver tissue samples were stained using hematoxylin-eosin staining, followed by iTRAQ quantitative proteomics to identify potential underlying therapeutic mechanisms and biomarkers. The results suggested that the expression levels of alanine transaminase, aspartate aminotransferase, total bilirubin and direct bilirubin were reduced in the rats treated with melatonin. Histopathological observation indicated that melatonin was effective in the treatment of ANIT-induced cholestasis. iTRAQ proteomics results suggested that melatonin-mediated reduction in ANIT-induced cholestasis may be associated with enhanced antioxidant function and relieving abnormal fatty acid metabolism. According to pathway enrichment analysis using the Kyoto Encyclopedia of Genes and Genomes, the major metabolic pathways for the metabolism of melatonin are fatty acid degradation, the peroxisome proliferator-activated receptor signaling pathway, fatty acid metabolism, chemical carcinogenesis, carbon metabolism, pyruvate metabolism, fatty acid biosynthesis and retinol metabolism, as well as drug metabolism via cytochrome P450. Malate dehydrogenase 1 and glutathione S-transferase Yb-3 may serve as potential targets in the treatment of ANIT-induced cholestasis with melatonin.

          Related collections

          Most cited references42

          • Record: found
          • Abstract: found
          • Article: not found

          Quantitative mass spectrometry in proteomics: critical review update from 2007 to the present.

          Marcus Bantscheff, Simone Lemeer, Mikhail M Savitski … (2012)
          Mass-spectrometry-based proteomics is continuing to make major contributions to the discovery of fundamental biological processes and, more recently, has also developed into an assay platform capable of measuring hundreds to thousands of proteins in any biological system. The field has progressed at an amazing rate over the past five years in terms of technology as well as the breadth and depth of applications in all areas of the life sciences. Some of the technical approaches that were at an experimental stage back then are considered the gold standard today, and the community is learning to come to grips with the volume and complexity of the data generated. The revolution in DNA/RNA sequencing technology extends the reach of proteomic research to practically any species, and the notion that mass spectrometry has the potential to eventually retire the western blot is no longer in the realm of science fiction. In this review, we focus on the major technical and conceptual developments since 2007 and illustrate these by important recent applications.
          Article 0 comments Cited 232 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Mechanisms of hepatotoxicity.

            H Jaeschke (2002)
            This review addresses recent advances in specific mechanisms of hepatotoxicity. Because of its unique metabolism and relationship to the gastrointestinal tract, the liver is an important target of the toxicity of drugs, xenobiotics, and oxidative stress. In cholestatic disease, endogenously generated bile acids produce hepatocellular apoptosis by stimulating Fas translocation from the cytoplasm to the plasma membrane where self-aggregation occurs to trigger apoptosis. Kupffer cell activation and neutrophil infiltration extend toxic injury. Kupffer cells release reactive oxygen species (ROS), cytokines, and chemokines, which induce neutrophil extravasation and activation. The liver expresses many cytochrome P450 isoforms, including ethanol-induced CYP2E1. CYP2E1 generates ROS, activates many toxicologically important substrates, and may be the central pathway by which ethanol causes oxidative stress. In acetaminophen toxicity, nitric oxide (NO) scavenges superoxide to produce peroxynitrite, which then causes protein nitration and tissue injury. In inducible nitric oxide synthase (iNOS) knockout mice, nitration is prevented, but unscavenged superoxide production then causes toxic lipid peroxidation to occur instead. Microvesicular steatosis, nonalcoholic steatohepatitis (NASH), and cytolytic hepatitis involve mitochondrial dysfunction, including impairment of mitochondrial fatty acid beta-oxidation, inhibition of mitochondrial respiration, and damage to mitochondrial DNA. Induction of the mitochondrial permeability transition (MPT) is another mechanism causing mitochondrial failure, which can lead to necrosis from ATP depletion or caspase-dependent apoptosis if ATP depletion does not occur fully. Because of such diverse mechanisms, hepatotoxicity remains a major reason for drug withdrawal from pharmaceutical development and clinical use.
            Article 0 comments Cited 217 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: found
              Is Open Access

              Melatonin as a Potent and Inducible Endogenous Antioxidant: Synthesis and Metabolism

              Dun-Xian Tan, Lucien Manchester, Eduardo Esteban-Zubero … (2015)
              Melatonin is a tryptophan-derived molecule with pleiotropic activities. It is present in almost all or all organisms. Its synthetic pathway depends on the species in which it is measured. For example, the tryptophan to melatonin pathway differs in plants and animals. It is speculated that the melatonin synthetic machinery in eukaryotes was inherited from bacteria as a result of endosymbiosis. However, melatonin’s synthetic mechanisms in microorganisms are currently unknown. Melatonin metabolism is highly complex with these enzymatic processes having evolved from cytochrome C. In addition to its enzymatic degradation, melatonin is metabolized via pseudoenzymatic and free radical interactive processes. The metabolic products of these processes overlap and it is often difficult to determine which process is dominant. However, under oxidative stress, the free radical interactive pathway may be featured over the others. Because of the complexity of the melatonin degradative processes, it is expected that additional novel melatonin metabolites will be identified in future investigations. The original and primary function of melatonin in early life forms such as in unicellular organisms was as a free radical scavenger and antioxidant. During evolution, melatonin was selected as a signaling molecule to transduce the environmental photoperiodic information into an endocrine message in multicellular organisms and for other purposes as well. As an antioxidant, melatonin exhibits several unique features which differ from the classic antioxidants. These include its cascade reaction with free radicals and its capacity to be induced under moderate oxidative stress. These features make melatonin a potent endogenously-occurring antioxidant that protects organisms from catastrophic oxidative stress.
              Article 0 comments Cited 206 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Journal
                Journal ID (nlm-ta): Exp Ther Med
                Journal ID (iso-abbrev): Exp Ther Med
                Journal ID (publisher-id): ETM
                Title: Experimental and Therapeutic Medicine
                Publisher: D.A. Spandidos
                ISSN (Print): 1792-0981
                ISSN (Electronic): 1792-1015
                Publication date (Print): September 2021
                Publication date (Electronic): 15 July 2021
                Publication date PMC-release: 15 July 2021
                Volume: 22
                Issue: 3
                Electronic Location Identifier: 1014
                Affiliations
                [1 ]Synopsis of Golden Chamber Department, Chinese Medicine College, Beijing University of Chinese Medicine, Beijing 100029, P.R. China
                [2 ]Formulas of Chinese Medicine, Basic Medical College of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 611137, P.R. China
                [3 ]Department of Pharmacology, Chinese Medicine College, Beijing University of Chinese Medicine, Beijing 100029, P.R. China
                Author notes
                Correspondence to: Professor Xianggen Zhong, Synopsis of Golden Chamber Department, Chinese Medicine College, Beijing University of Chinese Medicine, 11 North 3rd Ring East Road, Chaoyang, Beijing 100029, P.R. China zhongxg@ 123456bucm.edu.cn

                Professor Xiulan Deng, Department of Pharmacology, Chinese Medicine College, Beijing University of Chinese Medicine, 11 North 3rd Ring East Road, Chaoyang, Beijing 100029, P.R. China dengxiulan@ 123456bucm.edu.cn

                *Contributed equally

                Abbreviations: ALP, alkaline phosphatase; ALT, alanine transaminase; ANIT, α-naphthyl isothiocyanate; AST, aspartate transaminase; BP, biological processes; CC, cellular component; CMC, carboxymethyl cellulose sodium salt; DBIL, direct bilirubin; DTT, DL-dithiothreitol; FA, formic acid; GO, Gene Ontology; IA, iodoacetamide; iTRAQ, isobaric tags for relative and absolute quantitation; KEGG, Kyoto Encyclopedia of Genes and Genomes; LC-MS/MS, liquid chromatography-tandem mass spectrometry; MF, molecular function; PPAR, peroxisome proliferator-activated receptor; ROS, reactive oxygen species; TBIL, total bilirubin; TEAB, tetraethyl-ammonium bromide; UDCA, ursodeoxycholic acid

                Article
                Publisher ID: ETM-0-0-10446
                DOI: 10.3892/etm.2021.10446
                PMC ID: 8343461
                PubMed ID: 34373700
                SO-VID: 896fd47d-7732-4ff3-bf5d-9c2f2782e149
                Copyright © Copyright: © Wang et al.
                License:

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

                History
                Date received : 04 October 2019
                Date accepted : 28 April 2021
                Funding
                Funding: The present study was supported by the National Natural Science Foundation of China (grant no. 81573963).
                Categories
                Subject: Articles

                ScienceOpen disciplines: Medicine
                Keywords: melatonin,cholestasis,proteomics,itraq,anit
                Data availability:
                ScienceOpen disciplines: Medicine
                Keywords: melatonin, cholestasis, proteomics, itraq, anit

                Comments

                Comment on this article

                scite_

                Similar content1,329

                See all similar

                Cited by1

                See all cited by

                Most referenced authors607

                See all reference authors