Epigallocatechin gallate alleviates tetracycline-induced acute drug-induced liver injury by altering gut microbiota to modulate liver innate immune system
10.3760/cma.j.cn311367-20240604-00218
- VernacularTitle:表没食子儿茶素没食子酸酯通过改变肠道菌群调节肝脏固有免疫减轻四环素诱导的急性药物性肝损伤
- Author:
Siwen CHEN
1
;
Qing CHANG
1
;
Gangshi WANG
1
;
Yuan GONG
1
;
Haitao DU
1
;
Yi CHU
1
;
Shiping XU
1
Author Information
1. 中国人民解放军总医院第二医学中心消化内科 国家老年疾病临床医学研究中心，北京 100853
- Publication Type:Journal Article
- Keywords:
Drug-induced liver injury;
Epigallocatechin gallate;
Gut microbiota;
Mononuclear macrophages;
CD64
- From:
Chinese Journal of Digestion
2024;44(12):818-824
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the preventive and therapeutic effects of epigallocatechin gallate (EGCG) on tetracycline-induced acute drug-induced liver injury (DILI) in mice.Methods:Thirty-two BALB/C mice were divided into four groups, with eight mice in each group. The normal group was raised under conventional condition. Tetracycline-induced acute DILI models were established by intraperitoneal injection of tetracycline in the model group, the blank control group was intraperitoneally injected with equivalent 0.9% NaCl soluation, and EGCG prevention/treatment group was treated with EGCG on the basis of modeling. Blood samples, feces, liver and intestinal tissues of mice were obtained and analyzed by flow cytometry, biochemical test, pathological examination, and 16S rRNA sequencing. The effects of EGCG on gut microbiota, serum lipopolysaccharides (LPS) and transaminase, CD64 expression in intestinal mucosa, hepatic macrophage typing, and hepatic steatosis were evaluated. One-way analysis of variance was performed for analysis of significant difference among groups, and independent sample t test was used for further pairwise comparison. Results:Intraperitoneal injection of tetracycline-caused disorder of gut microbiota in the model group with hepatocytes showing steatosis grade 3 in 7 mice and grade 4 in 1 mouse. The serum level of LPS in model group was significantly higher than that of normal group ( (5.50±0.20) EU/L vs. (3.96±0.19) EU/L) and by the gut-liver axis which caused M1-type macrophages in liver tissues more than that of normal group ((40.00±2.91)% vs. (36.12±2.53)%), and the differences were statistically significant( t=15.83, 2.46; P<0.001, =0.034), and CD64 expression in intestinal mucosa also increased. EGCG intervention altered the gut microbiota in mice with tetracycline-induced acute DILI. The Shannon index and Simpson index of the model group were lower than those of the normal group (4.98±0.56 vs. 5.62±0.47, 0.91±0.03 vs. 0.95±0.02), while the Shannon index (4.08±0.62) and Simpson index (0.83±0.07) of the EGCG prevention/treatment group were lower than those of the model group. The differences were statistically significant ( t=-2.30, -2.85, -2.85, 2.82; P=0.038, 0.013, 0.013, 0.014). Compared with those of the model group, liver pathological changes of EGCG prevention/treatment group improved significantly (grade 2 in 8 mice), the serum level of LPS((4.22±0.17) EU/L) decreased, and the difference was statistically significant( t=-13.63, P<0.001), but had no significant effects on the CD64 expression in intestinal mucosa. Hepatic macrophage typing was compared between EGCG prevention/treatment group and model group, M2-type macrophages promoting repair were predominant in EGCG prevention/treatment group (M2-type macrophoges ratio: (6.20±0.17)% vs. (4.74±0.48)%, t=2.84, P=0.017; M1/M2-type macrophages ratio: 6.20±1.25 vs. 8.48±0.66, t=-4.95, P=0.001). Conclusion:EGCG alleviates tetracycline-induced acute DILI by altering gut microbiota to modulate liver innate immune system.
