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Roles of CYP2e1 in 1,2‐dichloroethane‐induced liver damage in mice
Author(s) -
Sun Qi,
Wang Gaoyang,
Gao Lanyue,
Shi Lei,
Qi Ying,
Lv Xiuqiang,
Jin Yaping
Publication year - 2016
Publication title -
environmental toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.813
H-Index - 77
eISSN - 1522-7278
pISSN - 1520-4081
DOI - 10.1002/tox.22148
Subject(s) - cyp2e1 , npsh , malondialdehyde , chemistry , microsome , liver injury , medicine , endocrinology , pharmacology , biochemistry , antioxidant , enzyme , glutathione
ABSTRACT 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/m 3 1,2‐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/m 3 1,2‐DCE group, and microsomal CYP2E1 protein expression and activity in both 0.45 and 0.9 g/m 3 1,2‐DCE groups increased significantly; conversely, hepatic nonprotein sulfhydryl (NPSH) levels in both 0.45 and 0.9 g/m 3 1,2‐DCE groups and hepatic SOD activities in 0.9 g/m 3 1,2‐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.