title: Metabolic influence of acute cyadox exposure on Kunming mice.
abstract: Cyadox is an antibiotic drug and has the potential to be used as a feedstuff additive in promoting the growth of animals. However, the toxicity of cyadox should be fully assessed before application, and this has prompted the current investigation on the metabolic responses of mice to cyadox exposure, using a metabonomic technique. Three groups of Kunming mice were respectively given a single dose of cyadox at three different concentrations (100, 650, and 4000 mg/kg body weight) via gavage. We present here the metabolic alterations of urine, plasma, liver, and renal medulla extracts induced by cyadox exposure. The metabolic alterations induced by cyadox exposure are dose-dependent, and metabolic recovery is achieved only for low and moderate levels of cyadox exposure during the experimental period. Cyadox exposure resulted in a disturbance of gut microbiota, which is manifested in depleted levels of urinary hippurate, trimethylamine-N-oxide (TMAO), dimethylamine (DMA), and trimethylamine (TMA). In addition, mice exposed to cyadox at high levels caused accumulations of amino acids and depletions of nucleotides in the liver. Furthermore, marked elevations of nucleotides and a range of organic osmolytes, such as myo-inositol, choline, and glycerophosphocholine (GPC), and decreased levels of amino acids are observed in the renal medulla of cyadox-exposed mice. These results suggest that cyadox exposure causes inhibition of amino acid metabolism in the liver and disturbance of gut microbiota community, influencing osmolytic homeostasis and nucleic acids synthesis in both the liver and the kidney. Our work provides a comprehensive view of the toxicological effects of cyadox, which is important in animal and human food safety.
authors.affiliation: Key Laboratory of Magnetic Resonance in Biological Systems, Wuhan Centre for Magnetic Resonance, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan 430071, People's Republic of China.
authors.forename: Chongyang
authors.initials: C
authors.lastname: Huang
authors.forename: Hehua
authors.initials: H
authors.lastname: Lei
authors.forename: Xiuju
authors.initials: X
authors.lastname: Zhao
authors.forename: Huiru
authors.initials: H
authors.lastname: Tang
authors.forename: Yulan
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000596:Amino Acids / Q000097:blood / Q000652:urine; D000818:Animals; D004123:Dimethylamines / Q000652:urine; D059022:Food Safety; D006626:Hippurates / Q000652:urine; D007679:Kidney Medulla / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008744:Methylamines / Q000652:urine; D051379:Mice; D009711:Nucleotides / Q000097:blood / Q000378:metabolism / Q000652:urine; D011810:Quinoxalines / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D000596:Amino Acids; D004123:Dimethylamines; D006626:Hippurates; D008744:Methylamines; D009711:Nucleotides; D011810:Quinoxalines; C020728:cyadox; C034516:dimethylamine; C005855:trimethyloxamine; C030514:hippuric acid