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Metabolic Response to Oral Microcystin-LR Exposure in the Rat by NMR-Based Metabonomic Study
He, Jun1; Chen, Jun1; Wu, Laiyan1,2; Li, Guangyu1,3; Xie, Ping1; Chen, J (reprint author), Chinese Acad Sci, Inst Hydrobiol, State Key Lab Freshwater Ecol & Biotechnol China, Donghu Expt Stn Lake Ecosyst, Donghu S Rd 7, Wuhan 430072, Peoples R China.
2012-12-01
Source PublicationJOURNAL OF PROTEOME RESEARCH
ISSN1535-3893
Volume11Issue:12Pages:5934-5946
AbstractMicrocystin-LR (MCLR), a potent hepatotoxin, is causing increased risks to public health. Although the liver is the main target organ of MCLR, the metabolic profiling of liver in response to MCLR in vivo remains unknown. Here, we comprehensively analyzed the metabolic change of liver and ileal flushes in rat orally gavaged with MCLR by H-1 nuclear magnetic resonance (NMR). Quantification of hepatic MCLR and its glutathione and cysteine conjugates by liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS) was conducted. Metabonomics results revealed significant associations of MCLR-induced disruption of hepatic metabolisms with inhibition of nutrient absorption, as evidenced by a severe decrease of 12 amino acids in the liver and their corresponding elevation in ileal flushes. The hepatic metabolism signature of MCLR was characterized by significant inhibition of tyrosine anabolism and catabolism, three disrupted pathways of choline metabolism, glutathione exhaustion, and disturbed nucleotide synthesis. Notably, substantial alterations of hepatic metabolism were observable even at the low MCLR-treated group (0.04 mg/kg MCLR), although no apparent histological changes in liver were observed in the low- and medium-dosed groups. These observations offered novel insights into the microcystin hepatotoxic mechanism at a functional level, thereby facilitating further assessment and clarification of human health risk from MCs exposure.; Microcystin-LR (MCLR), a potent hepatotoxin, is causing increased risks to public health. Although the liver is the main target organ of MCLR, the metabolic profiling of liver in response to MCLR in vivo remains unknown. Here, we comprehensively analyzed the metabolic change of liver and ileal flushes in rat orally gavaged with MCLR by H-1 nuclear magnetic resonance (NMR). Quantification of hepatic MCLR and its glutathione and cysteine conjugates by liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS) was conducted. Metabonomics results revealed significant associations of MCLR-induced disruption of hepatic metabolisms with inhibition of nutrient absorption, as evidenced by a severe decrease of 12 amino acids in the liver and their corresponding elevation in ileal flushes. The hepatic metabolism signature of MCLR was characterized by significant inhibition of tyrosine anabolism and catabolism, three disrupted pathways of choline metabolism, glutathione exhaustion, and disturbed nucleotide synthesis. Notably, substantial alterations of hepatic metabolism were observable even at the low MCLR-treated group (0.04 mg/kg MCLR), although no apparent histological changes in liver were observed in the low- and medium-dosed groups. These observations offered novel insights into the microcystin hepatotoxic mechanism at a functional level, thereby facilitating further assessment and clarification of human health risk from MCs exposure.
SubtypeArticle
KeywordMicrocystin-lr Metabonomics Nmr Glutathione Choline Nutrient Absorption
Department[He, Jun; Chen, Jun; Wu, Laiyan; Li, Guangyu; Xie, Ping] Chinese Acad Sci, Inst Hydrobiol, State Key Lab Freshwater Ecol & Biotechnol China, Donghu Expt Stn Lake Ecosyst, Wuhan 430072, Peoples R China; [Wu, Laiyan] S Cent Univ Nationalities, Coll Chem & Mat Sci, Wuhan 430074, Peoples R China; [Li, Guangyu] Huazhong Agr Univ, Coll Fisheries, Wuhan, Peoples R China
DOI10.1021/pr300685g
WOS HeadingsScience & Technology ; Life Sciences & Biomedicine
Funding OrganizationNational Natural Science Foundation of China [31070457] ; National Natural Science Foundation of China [31070457] ; National Natural Science Foundation of China [31070457] ; National Natural Science Foundation of China [31070457]
Indexed BySCI
Language英语
WOS Research AreaBiochemistry & Molecular Biology
WOS SubjectBiochemical Research Methods
WOS IDWOS:000311925900033
WOS KeywordTYPE-2A PROTEIN PHOSPHATASES ; GENE-EXPRESSION CHANGES ; HEPATOTOXIC MICROCYSTINS ; CARDIOVASCULAR-DISEASE ; GLUTATHIONE CONJUGATE ; QUANTITATIVE-ANALYSIS ; MOLECULAR-MECHANISMS ; INHIBITORY-ACTIVITY ; DNA METHYLATION ; BIGHEAD CARP
Funding OrganizationNational Natural Science Foundation of China [31070457] ; National Natural Science Foundation of China [31070457] ; National Natural Science Foundation of China [31070457] ; National Natural Science Foundation of China [31070457]
Citation statistics
Document Type期刊论文
Identifierhttp://ir.ihb.ac.cn/handle/342005/19301
Collection淡水生态学研究中心_期刊论文
Corresponding AuthorChen, J (reprint author), Chinese Acad Sci, Inst Hydrobiol, State Key Lab Freshwater Ecol & Biotechnol China, Donghu Expt Stn Lake Ecosyst, Donghu S Rd 7, Wuhan 430072, Peoples R China.
Affiliation1.Chinese Acad Sci, Inst Hydrobiol, State Key Lab Freshwater Ecol & Biotechnol China, Donghu Expt Stn Lake Ecosyst, Wuhan 430072, Peoples R China
2.S Cent Univ Nationalities, Coll Chem & Mat Sci, Wuhan 430074, Peoples R China
3.Huazhong Agr Univ, Coll Fisheries, Wuhan, Peoples R China
Recommended Citation
GB/T 7714
He, Jun,Chen, Jun,Wu, Laiyan,et al. Metabolic Response to Oral Microcystin-LR Exposure in the Rat by NMR-Based Metabonomic Study[J]. JOURNAL OF PROTEOME RESEARCH,2012,11(12):5934-5946.
APA He, Jun,Chen, Jun,Wu, Laiyan,Li, Guangyu,Xie, Ping,&Chen, J .(2012).Metabolic Response to Oral Microcystin-LR Exposure in the Rat by NMR-Based Metabonomic Study.JOURNAL OF PROTEOME RESEARCH,11(12),5934-5946.
MLA He, Jun,et al."Metabolic Response to Oral Microcystin-LR Exposure in the Rat by NMR-Based Metabonomic Study".JOURNAL OF PROTEOME RESEARCH 11.12(2012):5934-5946.
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