Abstract
Acute-on-chronic liver failure (ACLF) is a serious and complicated disease that threatens human health because its pathogenesis is unclear, and the outcome of the current therapies has been less than satisfactory. A national famous doctor of traditional Chinese medicine, Qian Ying, created the Jieduan-Niwan Formula (JDNW), based on his long-term clinical experience. However, despite the good clinical outcome, the biological mechanism by which it works is unknown. In the current study, we established an ACLF rat model by administering human serum albumin (HSA) combined with D-galactosamine (D-GalN) and lipopolysaccharide (LPS) to explore the potential mechanism of JDNW in treating ACLF. The rats were treated with JDNW by administration of the model substances and sacrificed after 4, 8, and 12 h. Then we divided the rats into normal group, model at 4 h, model at 8 h, model at 12 h, JDNW at 4 h, JDNW at 8 h, and JDNW at 12 h. Biochemical and histopathological examinations were performed to compare the rats in different groups. Compared with the ACLF model group, expression levels of alanine transaminase, aspartate aminotransferase, total bilirubin, and TNF-α and IL-6 proteins were reduced in the JDNW group at the corresponding time points, the survival rates of rats were increased, and the pathological condition of the liver was improved. In addition, JDNW treatment improved the ultrastructure of hepatocytes and mitochondria and decreased the hepatocyte apoptosis index. E2F1, P53, P73, Apaf-1, p14ARF, caspase-3, caspase-6, and caspase-7 levels in the JDNW group were distinctly lower than those in the untreated rats. Moreover, Bcl-2 and Mcl-1 levels increased. Thus, JDNW decreases ACLF-induced mortality in rats by modulating the E2F1-mediated intrinsic apoptotic pathway.
Highlights
Acute-on-chronic liver failure (ACLF) is a newly discovered clinical syndrome, characterized by early chronic liver disease or cirrhosis with organ failure. e 28-day mortality rate is high (50–90%) [1]
Compared to the control group, alanine transaminase (ALT), aspartate transaminase (AST), and total bilirubin (TBIL) levels in the ACLF model group were significantly and continuously increased through time (P < 0.01), which indicated the presence of severe liver damage
Apoptotic cells in the Jieduan-Niwan Formula (JDNW) group decreased at the corresponding time points. ese results suggested that JDNW could alleviate hepatocyte apoptosis and reduce the apoptotic index
Summary
Acute-on-chronic liver failure (ACLF) is a newly discovered clinical syndrome, characterized by early chronic liver disease or cirrhosis with organ failure. e 28-day mortality rate is high (50–90%) [1]. Acute-on-chronic liver failure (ACLF) is a newly discovered clinical syndrome, characterized by early chronic liver disease or cirrhosis with organ failure. Predisposing factors to develop the syndrome may be intrahepatic or extrahepatic, and potential chronic liver injury may occur whether or not the patient develops cirrhosis [2]. Once cirrhosis has transitioned from the compensated to the decompensated period, the short-term survival is 3–5 years. At this point, it is recommended to evaluate liver transplantation, except in the presence of contraindications [3]. Despite advances in medical treatment, clinical management of ACLF remains limited and challenging. Liver transplantation is the only option to save the patient’s life [4]
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