Therapeutic Potential of Plasma Proteins Derived from Umbilical Cord Blood for Acute Liver Failure
Journal
Molecular pharmaceutics
Journal Volume
16
Journal Issue
3
Pages
1092
Date Issued
2019-03
Author(s)
Abstract
There are very limited clinically viable treatment options for acute liver failure, a life-threatening condition that rapidly progresses to loss of liver function. In this study, we aim to evaluate the therapeutic potential of UCBP for acute liver failure induced in a rat model by D-galactosamine (GalN). F344 rats were randomly divided into two groups (control and UCBP-treated) after GalN injection. The therapeutic effects of UCBP were evaluated based on survival rate, H&E staining, TUNEL, PCNA staining, and in vivo BrdU labeling. Hepatocyte proliferation and the therapeutic mechanisms of UCBP were examined with BrdU and Western blot assay in vitro. The survival rate in the UCBP-treated group was found to be increased compared to the control group (85 vs 55%, P = 0.029). UCBP treatment significantly decreased apoptosis and increased cell proliferation. These effects may be secondary to specific bioactive molecules in UCBP. In vitro experiments revealed that adiponectin is one of the key biologically active components of UCBP in facilitating this result and promoting hepatocyte proliferation. Furthermore, this effect is mediated by p38/ERK mitogen-activated protein kinase (MAPK) signaling pathways. Therefore, this uncomplicated and clinically accessible approach may serve as effective bridge therapy for acute liver failure.
Subjects
acute liver failure; adiponectin; mitogen-activated protein kinase; umbilical cord blood plasma
SDGs
Other Subjects
adiponectin; adiponectin receptor 1; adiponectin receptor 2; cycline; galactosamine; mitogen activated protein kinase; mitogen activated protein kinase 1; mitogen activated protein kinase 3; mitogen activated protein kinase p38; plasma protein; protein kinase B; adiponectin; galactosamine; mitogen activated protein kinase p38; plasma protein; protein kinase B; acute liver failure; adult; Akt signaling; animal cell; animal experiment; animal model; animal tissue; apoptosis; Article; cell proliferation; controlled study; female; human; human cell; in vitro study; in vivo study; liver cell; liver injury; male; MAPK signaling; nonhuman; priority journal; rat; survival; survival rate; therapy effect; TUNEL assay; umbilical cord blood; Western blotting; acute liver failure; animal; cell line; cytology; disease model; drug effect; fetus blood; Fischer 344 rat; liver; metabolism; treatment outcome; Adiponectin; Animals; Apoptosis; Blood Proteins; Cell Line; Cell Proliferation; Disease Models, Animal; Fetal Blood; Galactosamine; Hepatocytes; Humans; Liver; Liver Failure, Acute; Male; MAP Kinase Signaling System; p38 Mitogen-Activated Protein Kinases; Proto-Oncogene Proteins c-akt; Rats; Rats, Inbred F344; Survival Rate; Treatment Outcome
Publisher
AMER CHEMICAL SOC
Type
journal article