Effect of blunting NF kappa B activation on CYP2 E1 in immunological liver injury rats
10.3969/j.issn.1001-1978.2015.08.010
- VernacularTitle:钝化NF-κB的活化对免疫性肝损伤大鼠CYP2 E1的影响
- Author:
Jinxue JIA
;
Jindong QIN
;
Xuefeng LI
;
Xiaolin KANG
;
Hongbo GAO
;
Yongzhi XUE
- Publication Type:Journal Article
- Keywords:
liver injury;
NF-κB;
PDTC;
CYP2 E1;
rat;
cytochrome P450;
Bacillus Calmette-Guerin
- From:
Chinese Pharmacological Bulletin
2015;(8):1076-1080
- CountryChina
- Language:Chinese
-
Abstract:
Aim To determine the function of nuclear factor-κB ( NF-κB ) in immunological liver injury of rat model and its effect on CYP2E1 expression, content and metabolic activity. Methods The immunological liver injury rat model was prepared by injection of Ba-cillus Calmette Guérin ( BCG,125 mg · kg-1 ) for 14 days. The hepatic tissue injury was revealed by hema-toxylin and eosin ( HE ) method and serum concentra-tion of alanine aminotransferase( ALT) , aspartate ami-notransferase ( AST ) respectively. CYP450 total con-tent in hepatic homogenate was determined by spectro-photography. The expression of CYP2E1 protein was detected by Western blot analysis. The enzyme kinetics of CYP2 E1 probe drug chlorzoxazone was evaluated by high-performance liquid chromatography ( HPLC ) as-say. Results The results showed that BCG-pretreat-ment ( 125 mg · kg-1 ) significantly increased the weight of liver and spleen, serum levels of ALT and AST(P<0. 01) , and decreased CYP2E1 expression, content and metabolic activity ( P <0. 05 ) . Adminis-tration of ammonium pyrrolidine dithiocarbamate (PDTC) (50, 100, 200 mg·kg-1) reversed the a-bove hepatic injury stimulated by BCG in vivo. Moreo-ver, PDTC dose-dependently inhibited the down regu-lation of CYP2 E1 ( P<0. 05 ) . Conclusion Passiva-tion of NF-κB can inhibit the down regulation of CYP2 E1 in liver tissue of immunological liver injury rats;NF-κB may be involved in CYP2 E1 down-regula-tion.
