Roles of CYP2e1 in 1,2-dichloroethane-induced liver damage in mice.
The aim of this study was to explore the roles of cytochrome P450 2E1 (CYP2E1) in 1,2-dichloroethane (1,2-DCE)-induced liver damage. Two parts were included in this study: first, effect of 1,2-DCE on microsomal expression of CYP2E1, and second, potential of an inhibitor of CYP2E1 to reduce 1,2-DCE-induced liver damage. In part one, mice were exposed to 0, 0.225, 0.45, or 0.9 g/m31,2-DCE for 10 days, 3.5 h per day through static inhalation. In part two, mice were divided into blank control, solvent control, inhibitor control, 1,2-DCE-poisoned group, and low or high intervention group. In part one, compared to the control, serum alanine aminotransferase (ALT) activities and hepatic malondialdehyde (MDA) levels in 0.9 g/m31,2-DCE group, and microsomal CYP2E1 protein expression and activity in both 0.45 and 0.9 g/m31,2-DCE groups increased significantly; conversely, hepatic nonprotein sulfhydryl (NPSH) levels in both 0.45 and 0.9 g/m31,2-DCE groups and hepatic SOD activities in 0.9 g/m31,2-DCE group decreased significantly. In part two, microsomal CYP2E1 protein expression and activity decreased significantly in both low and high intervention groups compared to 1,2-DCE-poisoned group. Along with the changes of CYP2E1, hepatic MDA levels and serum ALT activities decreased; conversely, hepatic NPSH levels and SOD activities increased significantly in high intervention group. Taken together, our results suggested that 1,2-DCE could enhance CYP2E1 protein expression and enzymatic activity, which could cause oxidative damage in liver, serving as an important mechanism underlying 1,2-DCE-induced liver damage. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1430-1438, 2016.
Department of Occupational and Environmental Health, School of Public Health, China Medical University, Shenyang, Liaoning, People's Republic of China.
Qi
Q
Sun
Department of Occupational and Environmental Health, School of Public Health, China Medical University, Shenyang, Liaoning, People's Republic of China.
Gaoyang
G
Wang
Department of Occupational and Environmental Health, School of Public Health, China Medical University, Shenyang, Liaoning, People's Republic of China.
Lanyue
L
Gao
Department of Occupational and Environmental Health, School of Public Health, China Medical University, Shenyang, Liaoning, People's Republic of China.
Lei
L
Shi
Department of Occupational and Environmental Health, School of Public Health, China Medical University, Shenyang, Liaoning, People's Republic of China.
Ying
Y
Qi
Department of Occupational and Environmental Health, School of Public Health, China Medical University, Shenyang, Liaoning, People's Republic of China.
Xiuqiang
X
Lv
Department of Occupational and Environmental Health, School of Public Health, China Medical University, Shenyang, Liaoning, People's Republic of China. jinyp@mail.cmu.edu.cn.
Yaping
Y
Jin
D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism / Q000502:physiology*; D005025:Ethylene Dichlorides / Q000633:toxicity*; D005260:Female; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D018675:Toxicity Tests
D005025:Ethylene Dichlorides; D008315:Malondialdehyde; C024565:ethylene dichloride; D019392:Cytochrome P-450 CYP2E1; D000410:Alanine Transaminase
1,2-dichloroethane poisoning; cytochrome P450 2E1; diallyl sulfide; liver damage; mice; oxidative damage