Role of dihydroceramides in the progression of acute-on-chronic liver failure in rats
10.1097/CM9.0000000000000601
- Author:
Li FANG-FANG
1
;
Liu NING
;
Liu WEI
;
Li MEI
;
Zhang FAN
;
Dong ZHEN
;
Zhang JIN-LAN
;
Sun HUA
Author Information
1. State Key Laboratory of Bioactive Substance and Function of Natural Medicines
- Keywords:
N-(4-hydroxyphenyl) retinamide;
Acute-on-chronic liver failure;
Ceramides;
Dihydroceramides
- From:
Chinese Medical Journal
2020;133(2):198-204
- CountryChina
- Language:Chinese
-
Abstract:
Background:Previously,dihydroceramide (d1 8:0/24:0) (dhCer (d1 8:0/24:0)) was reported to be a potential biomarker for acute-on-chronic liver failure (ACLF) prognosis.In this study,we further explored the role of dhCer (d18:0/24:0) in the progression of ACLF to validate the biomarker using ACLF rat model.Methods:ACLF rats were sacrificed at 4 and 8 h post-D-galactosamine (D-gal)/lipopolysaccharide (LPS) administration to investigate the liver biochemical markers,prothrombin time and liver histopathology.Change in dhCer and other sphingolipids levels were investigated by high-performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS).Rats were treated with N-(4-hydroxyphenyl) retinamide (4-HPR) to examine the mortality rate and its role in improving ACLF.Results:LPS/D-gal administration resulted in significant elevation in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels.Prothrombin time was prolonged and histopathological examination showed abnormality.HPLC-MS/MS results showed total dhCer levels in ACLF group (64.10 ± 8.90 pmol/100 μL,64.22 ± 6.78 pmol/100 μL for 4 and 8 h,respectively) were decreased significantly compared with control group (121.61 ± 23.09 pmol/100 μL) (P ＜ 0.05).In particular,dhCer (d18:0/24:0),dhCer (d18:0/20:0),and dhCer (d18:0/22:0) levels were decreased.Treatment with 4-HPR significantly increased the levels of dhCers,including dhCer (d18:0/24:0) compared with ACLF group,for the level of dhCer (d18:0/24:0) in 4-HPR group was 20.10 ± 8.60 pmol/100 μL and the level of dhCer (d18:0/24:0) in ACLF group was 9.74±2.99 pmol/100 μL (P ＜ 0.05).This was associated with reduced mortality rate and prolonged survival time.The ALT and AST in 4-HPR group were significandy decreased compared with ACLF group.The prothrombin time of 4-HPR group (41.49 s) was significantly lower than the prothrombin time of ACLF group (57.96 s) (P ＜ 0.05).4-HPR also decreased plasma ammonia levels slightly,as the plasma ammonia levels in 4-HPR group and ACLF group were 207.37 ± 60.43,209.15 ± 60.43 μmol/L,respectively.Further,4-HPR treatment improved histopathological parameters.Conclusions:DhCer,especially dhCer (d 18:0/24:0),is involved in the progression of ACLF.Increasing the levels of dhCer can reduce the mortality rate of ACLF rats and alleviate liver injury.
