Systems responses of rats to aflatoxin B1 exposure revealed with metabonomic changes in multiple biological matrices

Limin Zhang, Yangfang Ye, Yanpeng An, Yuan Tian, Yulan Wang, Huiru Tang

Research output: Contribution to journalArticlepeer-review

107 Scopus citations

Abstract

Exposure to aflatoxins causes liver fibrosis and hepatocellular carcinoma posing a significant health risk for human populations and livestock. To understand the mammalian systems responses to aflatoxin-B1 (AFB1) exposure, we analyzed the AFBI-induced metabonomic changes in multiple biological matrices (plasma, urine, and liver) of rats using 1H NMR spectroscopy together with clinical biochemistry and histopathologic assessments. We found that AFB1 exposure caused significant elevation of glucose, amino acids, and choline metabolites (choline, phosphocholine, and glycero-phosphocholine) in plasma but reduction of plasma lipids. AFB1 also induced elevation of liver lipids, amino acids (tyrosine, histidine, phenylalanine, leucine, isoleucine, and valine), choline, and nucleic acid metabolites (inosine, adenosine, and uridine) together with reduction of hepatic glycogen and glucose. AFB1 further caused decreases in urinary TCA cycle intermediates (2-oxoglutarate and citrate) and elevation of gut microbiota cometabolites (phenylacetylglycine and hippurate). These indicated that AFB1 exposure caused hepatic steatosis accompanied with widespread metabolic changes including lipid and cell membrane metabolisms, protein biosynthesis, glycolysis, TCA cycle, and gut microbiota functions. This implied that AFB1 exposure probably caused oxidative-stress-mediated impairments of mitochondria functions. These findings provide an overview of biochemical consequences of AFB1 exposure and comprehensive insights into the metabolic aspects of AFB1-induced hepatotoxicity in rats.

Original languageEnglish (US)
Pages (from-to)614-623
Number of pages10
JournalJournal of Proteome Research
Volume10
Issue number2
DOIs
StatePublished - Feb 4 2011

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Chemistry(all)

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