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Salidroside alleviates hepatic ischemia–reperfusion injury during liver transplant in rat through regulating TLR-4/NF-κB/NLRP3 inflammatory pathway

Authors :
Yanyao Liu
Zilun Lei
Hao Chai
Quan Kang
Xiaoyan Qin
Source :
Scientific Reports, Vol 12, Iss 1, Pp 1-12 (2022)
Publication Year :
2022
Publisher :
Nature Portfolio, 2022.

Abstract

Abstract Salidroside has anti-inflammatory, antioxidant and hepatoprotective properties. However, its effect on hepatic ischemia–reperfusion injury (IRI), an unavoidable side effect associated with liver transplantation, remains undefined. Here, we aimed to determine whether salidroside alleviates hepatic IRI and elucidate its potential mechanisms. We used both in vivo and in vitro assays to assess the effect and mechanisms of salidroside on hepatic IRI. Hepatic IRI rat models were pretreated with salidroside (5, 10 or 20 mg/kg/day) for 7 days following liver transplantation while hypoxia/reoxygenation (H/R) model of RAW 264.7 macrophages were pretreated with salidroside (1, 10 or 50 μM). The effect of salidroside on hepatic IRI was assessed using hematoxylin–eosin staining, terminal deoxynucleotidyl transferase dUTP nick-end labeling staining, qRT-PCR, immunosorbent assay and western blotting. Our in vivo assays showed that salidroside significantly reduced pathological liver damage, serum aminotransferase levels and serum levels of IL-1, IL-18 and TNF-α. Besides, salidroside reduced the expression of TLR-4/NF-κB/NLRP3 inflammatory pathway associated proteins (TLR-4, MyD88, p-IKKα, p-IKKβ, p-IKK, p-IκBα, p-P65, NLRP3, ASC, Cleaved caspase-1, IL-1β, IL-18, TNF-α and IL-6) in rats after liver transplantation. On the other hand, data from the in vitro analysis demonstrated that salidroside blocks expression of TLR-4/NF-κB/NLRP3 inflammatory pathway related proteins in the RAW264.7 cells treated with H/R. The salidroside-specific anti-inflammatory effects were partially inhibited by the TLR-4 agonist lipopolysaccharide. Taken together, our study showed that salidroside inhibits hepatic IRI following liver transplantation by modulating the TLR-4/NF-κB/NLRP3 inflammatory pathway.

Subjects

Subjects :
Medicine
Science

Details

Language :
English
ISSN :
20452322
Volume :
12
Issue :
1
Database :
Directory of Open Access Journals
Journal :
Scientific Reports
Publication Type :
Academic Journal
Accession number :
edsdoj.370f314c08af4cd68f57b9098f28f46a
Document Type :
article
Full Text :
https://doi.org/10.1038/s41598-022-18369-4