Role of dihydroceramides in the progression of acute-on-chronic liver failure in rats

Autor: Fang-Fang Li, Ning Liu, Wei Liu, Mei Li, Fan Zhang, Zhen Dong, Jin-Lan Zhang, Hua Sun, Li-Min Chen
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Chinese Medical Journal, Vol 133, Iss 2, Pp 198-204 (2020)
Druh dokumentu: article
ISSN: 0366-6999
2542-5641
00000000
DOI: 10.1097/CM9.0000000000000601
Popis: Abstract. Background. Previously, dihydroceramide (d18:0/24:0) (dhCer (d18:0/24:0)) 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
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