Broussonetiae Fructus Protects Against APAP-induced Liver Injury in Mice by Inhibiting Endoplasmic Reticulum Stress Pathway
10.13422/j.cnki.syfjx.20221544
- VernacularTitle:楮实子通过抑制内质网应激途径保护APAP诱导的小鼠肝损伤
- Author:
Jingmiao GAO
1
;
Tingting WANG
2
;
Yaning BIAO
1
;
Yaru GU
1
;
Muqing ZHANG
3
;
Xi WANG
1
;
Yixin ZHANG
1
Author Information
1. School of Pharmacy， International Joint Research Center on Resource Utilization and Quality Evaluation of Traditional Chinese Medicine（TCM）of Hebei Province， Application Technology Research and Development Center of TCM in Hebei Universities， Hebei University of Chinese Medicine， Shijiazhuang 050200， China
2. Cangzhou People's Hospital， Cangzhou 061000， China
3. Hebei Provincial Hospital of TCM， Shijiazhuang 050011， China
- Publication Type:Journal Article
- Keywords:
Broussonetiae Fructus;
acetaminophen;
drug-induced liver injury;
endoplasmic reticulum stress
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2022;28(16):66-73
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo explore the mechanism of Broussonetiae Fructus （BF） in preventing and treating drug-induced liver injury （DILI） induced by acetaminophen （APAP） through the endoplasmic reticulum stress pathway. MethodSixty C57BL/6N mice were randomly divided into normal group， model group， silybin group （3.4 g·kg-1）， and high-， medium- and low-dose BF groups （3.0， 1.5， 0.75 g·kg-1）， with 10 mice in each group. The DILI model was induced by intragastric administration of APAP at 800 mg·kg-1， and drugs were administered simultaneously for 10 consecutive days. The serum contents or activities of alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， total bilirubin （TBIL）， and direct bilirubin （DBIL） were measured. Hematoxylin-eosin（HE） staining was performed to observe the pathological changes in liver tissues. The morphological changes in liver mitochondria were observed by transmission electron microscopy. The activities or content of superoxide dismutase （SOD）， malondialdehyde （MDA）， total antioxidant capacity （T-AOC）， glutathione （GSH）， glutathione disulfide （GSSG）， glutathione peroxidase （GSH-Px）， and adenosine triphosphate （ATP） in the serum and liver tissues were detected by the colorimetric method. The expression of reactive oxygen species （ROS） in liver tissues was detected by immunofluorescence. The gene expression of glucose-regulated protein 78 （GRP78）， CCAAT/enhancer-binding protein homologous protein （CHOP）， and c-Jun N-terminal kinase （JNK） in liver tissues was detected by Real-time quantitative polymerase chain reaction （PCR）. ResultCompared with the normal group， the model group showed increased serum activities or content of ALT， AST， TBIL， and DBIL （P<0.01）， increased MDA and GSSG contents （P<0.01）， decreased contents or activities of SOD， T-AOC， GSH， GSH-Px， and ATP （P<0.01）， swollen hepatocytes with inflammatory infiltration and lamellar necrosis， swollen and broken mitochondria of hepatocytes， and increased mRNA expression of GRP78， CHOP， and JNK （P<0.01）. Compared with the model group， the groups with drug intervention showed decreased serum content or activities of ALT， AST， TBIL， and DBIL （P<0.05， P<0.01）， reduced MDA and GSSG contents（P<0.05， P<0.01）， and increased contents or activities of SOD， T-AOC， GSH， GSH-Px， and ATP （P<0.05， P<0.01）， improved swollen hepatocytes， inflammatory infiltration， and lamellar necrosis， recovered bilayer membrane structure in mitochondria of hepatocytes， and decreased mRNA expression of GRP78， CHOP， and JNK （P<0.05， P<0.01）. ConclusionBF has preventive and therapeutic effects on APAP-induced DILI mice， and the mechanism may be related to the reduction of endoplasmic reticulum stress and oxidative stress level in vivo.
