Mechanism of auraptene in improving acute liver injury induced by diquat poisoning in mice.
10.3760/cma.j.cn121430-20250113-00043
- Author:
Renyang OU
1
;
Shan HUANG
2
;
Lihong MA
1
;
Zhijie ZHAO
1
;
Shengshan LIU
1
;
Yuanliang WANG
1
;
Yezi SUN
1
;
Nana XU
3
;
Lijun ZHOU
3
;
Mei LI
4
;
Manhong ZHOU
1
;
Guosheng RAO
1
Author Information
1. Department of Emergency, Kweichow Moutai Hospital, Renhuai, Renhuai 564500, Guizhou, China.
2. Department of Intensive Care Medicine, Xishui County People's Hospital, Xishui 564600, Guizhou, China.
3. Department of Nursing, Affiliated Hospital of Zunyi Medical University, Zunyi 563000, Guizhou, China.
4. Hyperbaric Oxygen Treatment Center, Renhuai People's Hospital, Renhuai 564500, Guizhou, China. Corresponding author: Rao Guosheng, Email: 962235390@qq.com.
- Publication Type:Journal Article
- MeSH:
Animals;
Male;
Mice;
Mice, Inbred C57BL;
Liver/pathology*;
Chemical and Drug Induced Liver Injury/drug therapy*;
Diquat/poisoning*;
NF-E2-Related Factor 2/metabolism*;
Oxidative Stress;
Apoptosis;
Coumarins
- From:
Chinese Critical Care Medicine
2025;37(6):590-594
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To investigate whether auraptene (AUR) exerts a protective effect on acute diquat (DQ)-induced liver injury in mice and explore its underlying mechanisms.
METHODS:Forty SPF-grade healthy male C57BL/6 mice were randomly divided into normal control group (Control group), DQ poisoning model group (DQ group), AUR treatment group (DQ+AUR group), and AUR control group (AUR group), with 10 mice in each group. The DQ poisoning model was established via a single intraperitoneal injection of 40 mg/kg DQ aqueous solution (0.5 mL); Control group and AUR group received an equal volume of pure water intraperitoneally. Four hours post-modeling, DQ+AUR group and AUR group were administered 0.5 mg/kg AUR aqueous solution (0.2 mL) by gavage once daily for 7 consecutive days, while Control group and DQ group received pure water. Blood and liver tissues were collected after anesthesia on day 7. Liver ultrastructure was observed by transmission electron microscopy. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were measured via enzyme-linked immunosorbent assay (ELISA). Hepatic glutathione (GSH), superoxide dismutase (SOD), and malondialdehyde (MDA) levels were detected using WST-1, thiobarbituric acid (TBA), and enzymatic reaction methods, respectively. Protein expression of nuclear factor-erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), Kelch-like ECH-associated protein 1 (Keap1), and activated caspase-9 in liver tissues was analyzed by Western blotting.
RESULTS:Transmission electron microscopy revealed that mitochondria in the Control group exhibited mild swelling, uneven distribution of matrix, and a small number of cristae fractures. In the AUR group, mitochondria showed mild swelling, with no obvious disruption of cristae structure. In the DQ group, mitochondria demonstrated marked swelling and increased volume, matrix dissolution, loss and fragmentation of cristae, and extensive vacuolization. In contrast, the DQ+AUR group showed significantly reduced mitochondrial swelling, volume increase, matrix dissolution, cristae loss and fragmentation, and vacuolization compared to the DQ group. Compared with the DQ group, the DQ+AUR group exhibited significantly lower serum AST levels (U/L: 173.45±23.60 vs. 255.33±41.51), ALT levels (U/L: 51.77±21.63 vs. 100.70±32.35), and hepatic MDA levels (μmol/g: 12.40±2.76 vs. 19.74±4.10), along with higher hepatic GSH levels (mmol/g: 37.65±14.95 vs. 20.58±8.52) and SOD levels (kU/g: 124.10±33.77 vs. 82.81±22.00), the differences were statistically significant (all P < 0.05). Western blotting showed upregulated Nrf2 expression (Nrf2/β-actin: 0.87±0.37 vs. 0.53±0.22) and HO-1 expression (HO-1/β-actin: 1.06±0.22 vs. 0.49±0.08), and downregulated Keap1 expression (Keap1/β-actin: 0.82±0.12 vs. 1.52±0.76) and activated caspase-9 expression (activated caspase-9/β-actin: 1.16±0.28 vs. 1.71±0.30) in the DQ+AUR group compared to the DQ group (all P < 0.05).
CONCLUSION:AUR attenuates DQ-induced acute liver injury in mice by activating the Keap1/Nrf2 signaling pathway.
