title: Mechanism of adrenocortical toxicity induced by quinocetone and its bidesoxy-quinocetone metabolite in porcine adrenocortical cells in vitro.
abstract: Quinocetone (QCT) is a new feeding antibacterial agent in the QdNOs family. The mechanism of its adrenal toxicity is far from clear. This study was conducted to estimate the adrenal cell damage induced by QCT and its bidesoxy-quinocetone (B-QCT) metabolite and to further investigate their mechanisms. Following doses of QCT increasing from 5 to 50 μM, cell apoptosis and necrosis, mitochondrial dysfunction and redox imbalance were observed in porcine adrenocortical cells. The mRNA levels of the six components of intermediary enzymes and the adrenal renin-angiotensin-aldosterone system (RAAS) displayed a dysregulation induced by QCT, indicating that QCT might influence aldosterone secretion not only through the upstream of the production but also through the downstream of the adrenal RAAS pathway. In contrast, B-QCT had few toxic effects on the cell apoptosis, mitochondrial dysfunction and redox imbalance. Moreover, LCMS-IT-TOF analysis showed that no desoxy metabolites of QCT were found in either cell lysate or supernatant samples. In conclusion, we reported on the cytotoxicity in porcine adrenocortical cells exposed to QCT via oxidative stress, which raised awareness that its toxic effects resulted from N→O groups, and its toxic mechanism might involve the interference of the steroid hormone biosynthesis pathway.
authors: National Reference Laboratory of Veterinary Drug Residues (HZAU) and MAO Key Laboratory for Detection of Veterinary Drug Residues, China.
authors: Xu
authors: X
authors: Wang
authors: MOA Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products, Huazhong Agricultural University, Wuhan, Hubei 430070, China.
authors: Dan
authors: D
authors: Wan
authors: Department of Biosciences, COMSATS Institute of Information Technology, Sahiwal, Pakistan.
authors: Awais
authors: A
authors: Ihsan
authors: MOA Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products, Huazhong Agricultural University, Wuhan, Hubei 430070, China.
authors: Qianying
authors: Q
authors: Liu
authors: MOA Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products, Huazhong Agricultural University, Wuhan, Hubei 430070, China.
authors: Guyue
authors: G
authors: Cheng
authors: Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety, Wuhan, Hubei, China.
authors: Juan
authors: J
authors: Li
authors: Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety, Wuhan, Hubei, China.
authors: Zhenli
authors: Z
authors: Liu
authors: National Reference Laboratory of Veterinary Drug Residues (HZAU) and MAO Key Laboratory for Detection of Veterinary Drug Residues, 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: Zonghui
authors: Z
authors: Yuan
mesh_terms: D000302:Adrenal Cortex / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D000821:Animal Feed; D000818:Animals; D017849:Animals, Inbred Strains; D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001711:Biotransformation; D002478:Cells, Cultured; D002681:China; D005260:Female; D005503:Food Additives / Q000378:metabolism / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D007700:Kinetics; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008954:Models, Biological; D009336:Necrosis; D018384:Oxidative Stress / Q000187:drug effects; D011810:Quinoxalines / Q000378:metabolism / Q000494:pharmacology*; D012084:Renin-Angiotensin System / Q000187:drug effects; D034421:Sus scrofa
chemical_list: D000900:Anti-Bacterial Agents; D005503:Food Additives; D011810:Quinoxalines; C000609394:bidesoxy-quinocetone; C502851:quinocetone
keywords: Adrenal; Mechanism; Metabolite; QdNOs; Quinocetone; Toxicity