title: Systems responses of rats to mequindox revealed by metabolic and transcriptomic profiling.
abstract: Mequindox is used as an antibiotic drug in livestock; however, its toxicity remains largely unclear. Previously, we investigated metabolic responses of mice to mequindox exposure. In order to evaluate dependences of animal species in response to mequindox insult, we present the metabolic consequences of mequindox exposure in a rat model, by employing the combination of metabonomics and transcriptomics. Metabolic profiling of urine revealed that metabolic recovery is achieved for rats exposed to a low or moderate dose of mequindox, whereas high levels of mequindox exposure trigger liver dysfunction, causing no such recovery. We found that mequindox exposure causes suppression of the tricarboxylic acid cycle and stimulation of glycolysis, which is in contrast to a mouse model previously investigated. In addition, mequindox dosage induces promotion of β-oxidation of fatty acids, which was confirmed by elevated expressions of acox1, hsd17b2, and cpt1a in liver. Furthermore, altered levels of N-methylnicotinate, 1-methylnicotinamide, and glutathione disulfide highlighted the promotion of vitamin B3 antioxidative cycle in rats exposed to mequindox. Moreover, mequindox exposure altered levels of gut microbiotal related co-metabolites, suggesting a perturbation of the gut microflora of the host. Our work provides a comprehensive view of the toxicological effects of mequindox, which is important in the usage of mequindox in animal and human food safety.
authors: Wuhan Center of Magnetic Resonance, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences , Wuhan 430071, P. R. China.
authors: Xiu-Ju
authors: XJ
authors: Zhao
authors: Fuhua
authors: F
authors: Hao
authors: Chongyang
authors: C
authors: Huang
authors: Mattias
authors: M
authors: Rantalainen
authors: Hehua
authors: H
authors: Lei
authors: Huiru
authors: H
authors: Tang
authors: Yulan
authors: Y
authors: Wang
mesh_terms: D000818:Animals; D005260:Female; D020869:Gene Expression Profiling; D006651:Histocytochemistry; D016018:Least-Squares Analysis; D008099:Liver / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D053858:Metabolic Networks and Pathways; D055442:Metabolome / Q000187:drug effects*; D055432:Metabolomics; D019906:Nuclear Magnetic Resonance, Biomolecular; D009930:Organic Chemicals / Q000032:analysis / Q000097:blood / Q000652:urine; D025341:Principal Component Analysis; D011810:Quinoxalines / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D015203:Reproducibility of Results; D059467:Transcriptome / Q000187:drug effects*; D014556:Urine / Q000737:chemistry
chemical_list: C545385:Mequindox; D009930:Organic Chemicals; D011810:Quinoxalines