Effect and mechanism of safranal in a mouse model of sepsis-related liver injury induced by lipopolysaccharide

Yi CHEN; Yifan CHEN; Yichao DU; Peng TAN; Tongxi LI; Junjie BAI; Wenguang FU

doi:10.3969/j.issn.1001-5256.2023.11.019

Volume 39 Issue 11

Nov. 2023

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Article Navigation > Journal of Clinical Hepatology > 2023 > 39(11): 2643-2650

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Effect and mechanism of safranal in a mouse model of sepsis-related liver injury induced by lipopolysaccharide

DOI: 10.3969/j.issn.1001-5256.2023.11.019

Yi CHEN¹,
Yifan CHEN¹,
Yichao DU^{1, 2},
Peng TAN^{1, 2},
Tongxi LI¹,
Junjie BAI¹,
Wenguang FU^{1, 2
,
,
,}

1.
Department of General Surgery （Hepatopancreatobiliary Surgery），The Affiliated Hospital of Southwest Medical University，Luzhou，Sichuan 646000，China
2.
Academician （Expert） Workstation of Sichuan Province，Luzhou，Sichuan 646000，China

Research funding:

‍National Natural Science Foundation of China (82170587)

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Corresponding author: FU Wenguang， fuwg@swmu.edu.cn （ORCID： 0000-0003-3672-9728）
Received Date: 2023-02-19
Accepted Date: 2023-03-18
Published Date: 2023-11-28

Abstract

Abstract

Objective To investigate the protective effect of safranal against sepsis-related liver injury （SRLI） induced by lipopolysaccharide （LPS） in mice and its mechanism. Methods A 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）. Results After 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. Conclusion Safranal can exert a protective effect against SRLI induced by LPS in mice through the Nrf2/HO-1 pathway.
- ‍Sepsis,
- Liver Injury,
- Safranal,
- NF-E2-Related Factor 2,
- Heme Oxygenase-1

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References

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Effect and mechanism of safranal in a mouse model of sepsis-related liver injury induced by lipopolysaccharide

DOI: 10.3969/j.issn.1001-5256.2023.11.019

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