Kazinol B alleviates hypoxia/reoxygenation-induced hepatocyte injury by inhibiting the JNK signaling pathway.
10.11817/j.issn.1672-7347.2025.240524
- Author:
Yi ZHU
1
,
2
;
Junhui LI
1
;
Min YANG
1
;
Pengpeng ZHANG
1
;
Cai LI
1
;
Hong LIU
1
,
3
Author Information
1. Department of Organ Transplantation, Third Xiangya Hospital, Central South University, Changsha
2. 602809@csu.edu.cn.
3. 601941@csu.edu.cn.
- Publication Type:Journal Article
- Keywords:
Kazinol B;
antioxidative stress;
cytoprotection;
hepatocytes;
hypoxia/reoxygenation
- MeSH:
Animals;
Hepatocytes/pathology*;
Rats, Sprague-Dawley;
Male;
Rats;
Reperfusion Injury/prevention & control*;
Apoptosis/drug effects*;
Reactive Oxygen Species/metabolism*;
MAP Kinase Signaling System/drug effects*;
Cell Survival/drug effects*;
Cell Hypoxia;
Cells, Cultured
- From:
Journal of Central South University(Medical Sciences)
2025;50(2):181-189
- CountryChina
- Language:English
-
Abstract:
OBJECTIVES:Hypoxia/reoxygenation (H/R) injury is a critical pathological process during liver transplantation. Kazinol B has known anti-inflammatory, anti-apoptotic, and metabolic regulatory properties, but its protective mechanism in H/R-induced liver injury remains unclear. This study aims to investigate the protective effects and underlying mechanisms of Kazinol B in H/R-induced hepatocyte injury.
METHODS:An ischemia-reperfusion model was established in healthy adult male Sprague-Dawley rats, and an in vitro H/R model was created using cultured hepatocytes. Hepatocytes were treated with Kazinol B (0-100 μmol/L) to assess cytotoxicity and protective effects. Cell viability was evaluated using the cell counting kit-8 (CCK-8) and lactate dehydrogenase (LDH) release assays. Expression of apoptosis-related proteins, B-cell lymphoma 2 (Bcl-2), Bcl-2-associated death promoter (Bad), and cleaved caspase-3, was detected by Western blotting. Reactive oxygen species (ROS) levels were assessed via fluorescence probes, and inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were measured using enzyme-linked immunosorbent assay (ELISA). TdT-mediated nick end labeling (TUNEL) staining was performed to assess DNA damage and apoptosis.
RESULTS:Kazinol B had no significant effect on hepatocyte viability at 0-50 μmol/L, but showed cytotoxicity at 100 μmol/L (P<0.05). At 0.1-20 μmol/L, Kazinol B significantly improved cell survival, reduced LDH release, decreased apoptosis, and attenuated DNA damage (all P<0.001). At 10 μmol/L, Kazinol B markedly down-regulated Bad and cleaved caspase-3 (both P<0.05), and up-regulated Bcl-2 (P<0.01). It also dose-dependently reduced ROS levels and inflammatory cytokines TNF-α and IL-1β (all P<0.01). Both in vitro and in vivo, Kazinol B inhibited activation of the c-Jun N-terminal kinase (JNK) pathway without affecting extracellular regulated protein kinase (ERK) signaling (P>0.05). TUNEL staining showed that the protective effect of Kazinol B against apoptosis was partially reversed by the JNK agonist anisomycin (P<0.01).
CONCLUSIONS:Kazinol B mitigates hepatocyte injury induced by H/R by inhibiting the JNK signaling pathway. Its protective effect is associated with suppression of oxidative stress and inflammation, indicating its potential as a hepatoprotective agent.
