Effect and mechanism of safranal in a mouse model of sepsis-related liver injury induced by lipopolysaccharide
10.3969/j.issn.1001-5256.2023.11.019
- VernacularTitle:藏红花醛对脂多糖诱导的脓毒症相关肝损伤小鼠模型的作用及其机制
- Author:
Yi CHEN
1
;
Yifan CHEN
1
;
Yichao DU
1
;
Peng TAN
1
;
Tongxi LI
1
;
Junjie BAI
1
;
Wenguang FU
1
Author Information
1. Department of General Surgery （Hepatopancreatobiliary Surgery）， The Affiliated Hospital of Southwest Medical University， Luzhou， Sichuan 646000， China
- Publication Type:Journal Article
- Keywords:
Sepsis;
Liver Injury;
Safranal;
NF-E2-Related Factor 2;
Heme Oxygenase-1
- From:
Journal of Clinical Hepatology
2023;39(11):2643-2650
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo investigate the protective effect of safranal against sepsis-related liver injury （SRLI） induced by lipopolysaccharide （LPS） in mice and its mechanism. MethodsA total of 32 experimental male C57BL/6 mice were divided into control group， single drug group， model group， and treatment group using the simple random method， with 8 mice in each group. The mice in the single drug group and the treatment group were intraperitoneally injected with safranal （60 mg/kg） for 7 days of pretreatment， and the mice in the model group and the treatment group were intraperitoneally injected with LPS （10 mg/kg） to induce acute liver injury. The activities of serum alanine aminotransferase （ALT） and aspartate aminotransferase （AST） were measured； HE staining was used to observe liver tissue sections； immunohistochemistry was used to analyze the expression of the downstream protein heme oxygenase-1 （HO-1） in the signal pathway； TUNEL was used to analyze the apoptosis of hepatocytes； Western blot was used to measure the expression of total proteins （nuclear factor erythroid 2-related factor 2 ［Nrf-2］ and HO-1） in liver tissue. The human liver cell line L02 was pretreated with safranal （100 μmol/L）， followed by induction of acute hepatocellular injury with LPS （100 ng/mL）， and DCFH-DA fluorescent labeling was used to detect reactive oxygen species （ROS）. ResultsAfter safranal pretreatment， the treatment group had significantly lower levels of ALT and AST than the model group （both P<0.001）， with a relatively intact pseudolobular structure and a smaller necrotic area in the liver. Compared with the model group， the treatment group had significant increases in the expression levels of Nrf2 and HO-1 in liver tissue after safranal+LPS treatment （both P<0.001）， and immunohistochemistry showed that safranal pretreatment increased the number of HO-1-positive cells. In the cell model of LPS-induced acute liver injury， the treatment group had a significant reduction in the production of ROS compared with the model group. ConclusionSafranal can exert a protective effect against SRLI induced by LPS in mice through the Nrf2/HO-1 pathway.
