title: The mechanism of enzymatic and non-enzymatic N-oxide reductive metabolism of cyadox in pig liver.
abstract: Cyadox is a novel quinoxaline-1,4-dioxide with the potential for development as a substitute for the banned veterinary drugs carbadox and olaquindox. In this paper, using pigs as the test subjects, the metabolic mechanism of cyadox N-oxide reduction in liver is demonstrated.        There exist two metabolic mechanisms for the N-oxide reduction of cyadox, the enzymatic and non-enzymatic routes. It is found that cyadox can be enzymatically reduced to 4-cyadox monoxide and 1-cyadox monoxide; this process is catalyzed by aldehyde oxidase and xanthine oxidase in the cytosol and by cytochrome b5 reductase in the microsomes. On the other hand, cyadox is only reduced to 4-cyadox monoxide in the non-enzymatic reduction mediated by heme groups of catalase and cytochrome P450s.        We supposed that, owing to the position of the side chain in cyadox, the 1-N-oxide and 4-N-oxide bonds in the quinoxaline ring had different biochemical activities, which caused cyadox to be shunted to the distinct metabolic mechanisms. Additionally, this research gives the first evidence of FAD- and NAD(P)H-dependent non-enzymatic catalase reduction of a heterocyclic N-oxide. The research provides a basic foundation for the formulation of safety controls for animal products and the properties and metabolism of heterocyclic N-oxides.
authors: College of Life Sciences, South China Agricultural University, Guangzhou 510642, China.
authors: Ming
authors: M
authors: Zheng
authors: Jun
authors: J
authors: Jiang
authors: Junping
authors: J
authors: Wang
authors: Xianqing
authors: X
authors: Tang
authors: Man
authors: M
authors: Ouyang
authors: Yiqun
authors: Y
authors: Deng
mesh_terms: D000818:Animals; D002374:Catalase / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D003600:Cytosol / Q000201:enzymology; D006420:Hemeproteins / Q000378:metabolism; D008099:Liver / Q000201:enzymology* / Q000378:metabolism*; D008862:Microsomes, Liver / Q000201:enzymology; D010084:Oxidation-Reduction; D010087:Oxides / Q000378:metabolism*; D011810:Quinoxalines / Q000737:chemistry / Q000378:metabolism; D011994:Recombinant Proteins; D034421:Sus scrofa
chemical_list: D006420:Hemeproteins; D010087:Oxides; D011810:Quinoxalines; D011994:Recombinant Proteins; C020728:cyadox; D003577:Cytochrome P-450 Enzyme System; D002374:Catalase