Document Detail

Metabolic Response to Oral Microcystin-LR Exposure in the Rat by NMR-based Metabonomic study.
MedLine Citation:
PMID:  23145862     Owner:  NLM     Status:  Publisher    
Microcystin-LR (MCLR), a potent hepatotoxin, is causing increasing risk to public health. Although 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 (1)H 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 severe decrease of 12 amino acids in liver and their corresponding elevation in ileal flushes. 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 microcystin hepatotoxic mechanism at functional level, thereby facilitating further assessment and clarification of human health risk from MCs exposure.
Jun He; Jun Chen; Laiyan Wu; Guangyu Li; Ping Xie
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-11-13
Journal Detail:
Title:  Journal of proteome research     Volume:  -     ISSN:  1535-3907     ISO Abbreviation:  J. Proteome Res.     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-13     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101128775     Medline TA:  J Proteome Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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