Therapeutic Potential of Plasma Proteins Derived from Umbilical Cord Blood for Acute Liver Failure

Mol Pharm. 2019 Mar 4;16(3):1092-1104. doi: 10.1021/acs.molpharmaceut.8b01108. Epub 2019 Feb 13.

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.

Keywords: acute liver failure; adiponectin; mitogen-activated protein kinase; umbilical cord blood plasma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adiponectin / therapeutic use*
  • Animals
  • Apoptosis / drug effects
  • Blood Proteins / therapeutic use*
  • Cell Line
  • Cell Proliferation / drug effects
  • Disease Models, Animal
  • Fetal Blood*
  • Galactosamine / pharmacology
  • Hepatocytes / metabolism
  • Humans
  • Liver / cytology
  • Liver Failure, Acute / chemically induced
  • Liver Failure, Acute / therapy*
  • MAP Kinase Signaling System
  • Male
  • Proto-Oncogene Proteins c-akt / metabolism
  • Rats
  • Rats, Inbred F344
  • Survival Rate
  • Treatment Outcome
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Adiponectin
  • Blood Proteins
  • Galactosamine
  • Proto-Oncogene Proteins c-akt
  • p38 Mitogen-Activated Protein Kinases