title: Evaluation of the safety of primary metabolites of cyadox: Acute and sub-chronic toxicology studies and genotoxicity assessment.
abstract: Cyadox (CYA) is a synthetic antimicrobial agent, belonging to quinoxaline (QdNO) family. Cy1 (bidesoxy cyadox), Cy2 (N4-desoxycyadox) and Cy10 (N1-desoxycyadox) are the primary metabolites of CYA. In our present study, an acute toxicity test, a sub-chronic toxicity test, and a battery of three genotoxicity tests were carried out according to standard protocols. The LD50 of the metabolites were above 5000 mg/kg b.w. The maximum tolerated dose (MTD) of Cy1 and Cy-M (mixture of Cy2 and Cy10) in rats, and the MTD of Cy1, Cy2 and Cy10 in mice were above 6000 mg/kg b.w./day. In subchronic study, rats were separately administered Cy1 and Cy-M at the dose levels of 0, 50, 150 and 2500 mg/kg diet for 90 days, with CYA (2500 mg/kg) as a control. Significant decreases in body weight and changes in clinical serum biochemistry were observed in the high-dose group of Cy1 and Cy-M, as well as CYA. Significant changes in relative weights of organs at 150 and 2500 mg/kg diet of Cy1 and CYA were noted. Additionally, the high-dose groups of Cy1, Cy-M and CYA showed pathological changes near the hepatic portal area. There was no evidence for genotoxic activity of any of the three metabolites in the bacterial reverse mutation test, mouse bone marrow micronucleus assay or an in vitro assay for clastogenicity. Based on the subchronic study, the target organ of the primary metabolites was the liver, and the no-observed-adverse-effect level for Cy1 and Cy-M was 150 mg/kg diet.
authors.affiliation: National Reference Laboratory of Veterinary Drug Residues (HZAU) and MAO Key Laboratory for Detection of Veterinary Drug Residues, Wuhan, Hubei 430070, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Huang
authors.affiliation: Department of Biosciences, COMSATS Institute of Information Technology, Sahiwal, Pakistan.
authors.forename: Awais
authors.initials: A
authors.lastname: Ihsan
authors.affiliation: MOA Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products, Huazhong Agricultural University, Wuhan, Hubei 430070, China.
authors.forename: Pu
authors.initials: P
authors.lastname: Guo
authors.affiliation: MOA Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products, Huazhong Agricultural University, Wuhan, Hubei 430070, China.
authors.forename: Xun
authors.initials: X
authors.lastname: Luo
authors.affiliation: Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety, Wuhan, Hubei, China.
authors.forename: Guyue
authors.initials: G
authors.lastname: Cheng
authors.affiliation: Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety, Wuhan, Hubei, China.
authors.forename: Haihong
authors.initials: H
authors.lastname: Hao
authors.affiliation: Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety, Wuhan, Hubei, China.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Chen
authors.affiliation: Department of Biosciences, COMSATS Institute of Information Technology, Sahiwal, Pakistan.
authors.forename: Farrukh
authors.initials: F
authors.lastname: Jamil
authors.affiliation: Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety, Wuhan, Hubei, China.
authors.forename: Yanfei
authors.initials: Y
authors.lastname: Tao
authors.affiliation: Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety, Wuhan, Hubei, China. Electronic address: wangxu@mail.hzau.edu.cn.
authors.forename: Xu
authors.initials: X
authors.lastname: Wang
authors.affiliation: National Reference Laboratory of Veterinary Drug Residues (HZAU) and MAO Key Laboratory for Detection of Veterinary Drug Residues, Wuhan, Hubei 430070, China; MOA Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products, Huazhong Agricultural University, Wuhan, Hubei 430070, China; Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety, Wuhan, Hubei, China. Electronic address: yuan5802@mail.hzau.edu.cn.
authors.forename: Zonghui
authors.initials: Z
authors.lastname: Yuan
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000378:metabolism / Q000633:toxicity*; D015415:Biomarkers / Q000097:blood; D001711:Biotransformation; D004305:Dose-Response Relationship, Drug; D005260:Female; D007928:Lethal Dose 50; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D020714:Maximum Tolerated Dose; D008807:Mice, Inbred BALB C; D048629:Micronuclei, Chromosome-Defective / Q000139:chemically induced; D015162:Micronucleus Tests; D009152:Mutagenicity Tests; D009929:Organ Size / Q000187:drug effects; D011810:Quinoxalines / Q000378:metabolism / Q000633:toxicity; D017208:Rats, Wistar; D018570:Risk Assessment; D013997:Time Factors; D023382:Toxicity Tests, Acute; D059550:Toxicity Tests, Subchronic; D015431:Weight Loss / Q000187:drug effects
chemical_list: D000890:Anti-Infective Agents; D015415:Biomarkers; D011810:Quinoxalines; C020728:cyadox
keywords: Acute toxicity; Cyadox; Genotoxicity; Metabolites; Quinoxaline; Subchronic toxicity