Systems responses of rats to mequindox revealed by metabolic and transcriptomic profiling.
J Proteome Res
; 11(9): 4712-21, 2012 Sep 07.
Article
em En
| MEDLINE
| ID: mdl-22845897
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 ß-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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Quinoxalinas
/
Metaboloma
/
Transcriptoma
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
J Proteome Res
Assunto da revista:
BIOQUIMICA
Ano de publicação:
2012
Tipo de documento:
Article