2. Academic Validation
  3. Quinocetone-induced Nrf2/HO-1 pathway suppression aggravates hepatocyte damage of Sprague-Dawley rats

Quinocetone-induced Nrf2/HO-1 pathway suppression aggravates hepatocyte damage of Sprague-Dawley rats

  • Food Chem Toxicol. 2014 Jul:69:210-9. doi: 10.1016/j.fct.2014.04.026.
Miao Yu 1,  Di Wang 1,  Mengjing Xu 1,  Yang Liu 1,  Xia Wang 1,  Jun Liu 1,  Xuefeng Yang 1,  Ping Yao 1,  Hong Yan 2,  Liegang Liu 3
Affiliations

Affiliations

  • 1 Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030, China; Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030, China.
  • 2 Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030, China. Electronic address: yanhong@mails.tjmu.edu.cn.
  • 3 Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030, China; Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030, China. Electronic address: lgliu@mails.tjmu.edu.cn.
PMID: 24795230 DOI: 10.1016/j.fct.2014.04.026
Abstract

Quinocetone (3-methyl-2-quinoxalin benzenevinylketo-1,4-dioxide, QCT) is a widely used veterinary drug in PR China that promotes feed efficiency and growth of various Animals. However, its potential toxicity has been concerned recently. In the present study, we investigated QCT-induced hepatocyte changes and its related mechanism, especially the expression of Nrf2/HO-1 pathway. Oxidative stress induced by QCT in hepatocyte led to DNA damage, inflammation and Apoptosis. Nevertheless, hepatocyte has a self-repair system to protect itself from oxidative stress. In the 50 mg/kg/day QCT group, the morphology and function of liver were approximately maintained on normal level, which indicated that the damaged cell might have a self-repair mechanism. Notably, nuclear factor-erythroid 2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) pathway plays a critical role in protecting cells against Reactive Oxygen Species (ROS) generation. However, higher doses of QCT (800 mg/kg/day and 2400 mg/kg/day) inhibited the expression of Nrf2/HO-1 pathway, which resulted in excessive ROS generation and irreversible oxidative DNA damage, inflammation and Apoptosis. In conclusion, although QCT-induced oxidative stress activates the expression of Nrf2/HO-1 pathway initially, persistent QCT exposure will inhibit this expression and aggravate hepatocyte damage. Simultaneously, inflammation and Apoptosis continues to progress, liver dysfunction and tissue damage will be occurred eventually.

Keywords

Nrf2/HO-1 pathway; Oxidative stress; Quinocetone.

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