title: Systems responses of rats to aflatoxin B1 exposure revealed with metabonomic changes in multiple biological matrices.
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 AFB1-induced metabonomic changes in multiple biological matrices (plasma, urine, and liver) of rats using (1)H 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 glycerophosphocholine) 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.
authors.affiliation: State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan, P R China.
authors.forename: Limin
authors.initials: L
authors.lastname: Zhang
authors.forename: Yangfang
authors.initials: Y
authors.lastname: Ye
authors.forename: Yanpeng
authors.initials: Y
authors.lastname: An
authors.forename: Yuan
authors.initials: Y
authors.lastname: Tian
authors.forename: Yulan
authors.initials: Y
authors.lastname: Wang
authors.forename: Huiru
authors.initials: H
authors.lastname: Tang
mesh_terms: D016604:Aflatoxin B1 / Q000633:toxicity*; D000596:Amino Acids / Q000032:analysis / Q000378:metabolism; D000818:Animals; D002794:Choline / Q000378:metabolism; D006651:Histocytochemistry; D016018:Least-Squares Analysis; D050356:Lipid Metabolism / Q000187:drug effects; D008099:Liver / Q000737:chemistry* / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D055442:Metabolome / Q000187:drug effects*; D055432:Metabolomics; D019906:Nuclear Magnetic Resonance, Biomolecular; D010949:Plasma / Q000737:chemistry* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D014556:Urine / Q000737:chemistry*
chemical_list: D000596:Amino Acids; D016604:Aflatoxin B1; D002794:Choline