title: Dynamic metabolic response of mice to acute mequindox exposure.
abstract: Mequindox is used as a veterinary antibiotic drug. As part of systematic investigations into mequindox as a veterinary medicine and its subsequent applications in food safety, we conducted the investigation to assess the metabolic response of mice to mequindox using metabonomics, which combines NMR metabolic profiles of biofluids or tissues and pattern recognition data analysis. In this study, we delivered a single dose of mequindox to mice with dosage levels of 15, 75, and 350 mg/kg body weight and collected urine samples over a 7 day period, as well as plasma and liver tissues at 7 days postdose. Principal components analysis (PCA) and orthogonal projection to latent structure discriminant analysis (O-PLS-DA) were performed on (1)H NMR spectra of biofluids and liver, showing that low dose levels of mequindox exposure had no adverse effects, consistent with histological observations of the liver. High and moderate levels of mequindox exposure caused suppression of glycolysis and stimulation of fatty acid oxidation accompanied with increased levels of oxidative stress. Our metabonomic analyses also showed disruption of amino acid metabolism, consistent with liver damage observed from histopathological examinations. Furthermore, mequindox perturbed gut microbial activity manifested in the altered excretion of urinary trimethylamine (TMA), trimethylamine-N-oxide (TMAO), hippurate, phenylacetylglycine (PAG), and phenylacetate. The putative gut microbial function may also contribute to the assembly and secretion of very-low-density lipoproteins from the liver to the plasma. Our work provides important insights on the metabolic responses of mequindox.
authors: Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences , Wuhan 430071, People's Republic of China.
authors: Xiu-Ju
authors: XJ
authors: Zhao
authors: Chongyang
authors: C
authors: Huang
authors: Hehua
authors: H
authors: Lei
authors: Xiu
authors: X
authors: Nie
authors: Huiru
authors: H
authors: Tang
authors: Yulan
authors: Y
authors: Wang
mesh_terms: D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D000900:Anti-Bacterial Agents / Q000633:toxicity*; D001786:Blood Glucose / Q000378:metabolism; D002952:Citric Acid Cycle / Q000187:drug effects; D005260:Female; D005998:Glycine / Q000031:analogs & derivatives / Q000652:urine; D006626:Hippurates / Q000652:urine; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D055442:Metabolome / Q000187:drug effects*; D008744:Methylamines / Q000652:urine; D051379:Mice; D025341:Principal Component Analysis; D011810:Quinoxalines / Q000633:toxicity*
chemical_list: D000596:Amino Acids; D000900:Anti-Bacterial Agents; D001786:Blood Glucose; D006626:Hippurates; C545385:Mequindox; D008744:Methylamines; D011810:Quinoxalines; C022050:phenylacetylglycine; C005855:trimethyloxamine; C023336:trimethylamine; C030514:hippuric acid; D005998:Glycine