To explore the mechanism of acetaminophen liver injury in children based on MCJ as the target
10.3760/cma.j.cn115455-20240508-00385
- VernacularTitle:基于MCJ靶点探讨对乙酰氨基酚致儿童药物性肝损伤的机制
- Author:
Zhe LI
1
;
Liu JI
;
Rui WANG
;
Li WANG
;
Hua LI
Author Information
1. 大连市妇女儿童医疗中心（集团）药剂科，大连 116033
- Keywords:
Chemical and drug induced liver injury;
Child;
Acetaminophen;
Target
- From:
Chinese Journal of Postgraduates of Medicine
2024;47(11):1013-1019
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the characteristics of drug-induced liver injury induced by acetaminophen (APAP) in children, and to clarify the mechanism of improving APAP liver injury in children on targeting MCJ.Methods:The C57BL/6 young and adult mice and mouse liver parenchymal AML-12 cells were used in the prospective study. Forty C57BL/6 young mice of 3 to 4 weeks and 40 C57BL/6 adult mice of 6 to 8 weeks were randomly divided into 5 groups (control 0 h group, APAP 3 h group, APAP 6 h group, APAP 12 h group, APAP 24 h group), 8 rats in each group and intraperitoneally injected with APAP (300 mg/kg) to replicate drug-induced liver injury (DILI) model. The serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were detected. Hematoxylin-eosin staining (H&E) staining was used to observe the pathological change of liver tissue. The oxidative damage indexes lactate dehydrogenase (LDH), malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD) of liver tissue homogenate were detected. The expression of MCJ protein was detected by Western blot. Mouse liver parenchymal AML-12 cells were transfected with MCJ interference sequence and APAP to construct hepatocyte injury model. Hepatocyte viability, LDH and SOD levels were measured.Results:As shown in the animals results, after 3 h of APAP administration, ALT and AST levels were increased significantly in young mice, compared with adult mice: (105.25 ± 18.38) U/L vs. (37.38 ± 15.75) U/L, (87.38 ± 30.68) U/L vs. (28.50 ± 19.44)U/L, which suggested that the time liver necrosis occurred in young mice was earlier than that of adult mice. Moreover, the levels of LDH and MDA were significantly increased, while GSH and SOD were significantly decreased after 3 h of APAP in young mice, compared with adult mice, (1 231.38 ± 183.94) U/L vs. (810.50 ± 190.64) U/L, (19.63 ± 3.58) nmol/mg vs. (16.50 ± 3.51) nmol/mg, (39.75 ± 4.62) nmol/mg vs. (53.63 ± 13.07) nmol/mg, (51.38 ± 6.37)% vs. (63.25 ± 9.13)% ( P<0.01), and the levels of MCJ protein were significantly increased. After MCJ knockdown, hepatocyte viability and LDH, SOD levels of mouse liver parenchymal AML-12 cells were significantly improved compared with APAP model group ( P<0.01). Conclusions:APAP liver injury was more common in young mice than in adult mice. Knockdown MCJ expression may ameliorate APAP liver injury in young mice. MCJ may serve as a target for early intervention of APAP liver injury in children, which provide new therapeutic targets and strategies for APAP liver injury in children.
