Ursolic Acid Improves Liver Transplantation and Inhibits Apoptosis in Miniature Pigs Using Donation After Cardiac Death

Cell Physiol Biochem. 2017;43(1):331-338. doi: 10.1159/000480413. Epub 2017 Aug 31.

Abstract

Background: Ursolic acid (UA) possesses extensive pharmacological activities, including anti-oxidation, anti-infection, anti-inflammation, anti-tumor, liver protection. This study was designed to investigate the effect of UA on liver transplantation after liver transplantation using donation after cardiac death (DCD), and to assess the mechanisms.

Methods: 24 healthy experimental pigs were randomly divided into control and experimental groups. Each group received six DCD liver transplantations. In the experimental group, the recipient pigs received 120 mg/kg UA 4 h before surgery by intraperitoneal injection. The liver tissues and vein blood were collected 0 h, 1 h, 3 h, 6 h, 12 h and 24 h after transplantation. Morphological change, malondialdehyde (MDA) level, protein kinase-like ER kinase (PERK)-CHOP signaling pathway and apoptosis in liver tissue and serum aminotransferase (ALT) level were assessed.

Results: Compared with control group, ALT level was significantly decreased (P<0.05) and pathological changes in liver were ameliorated in experimental group. UA treatment also decreased MDA level in liver tissue and attenuated the apoptosis. Compared with control group, Bax decreased and Bcl-2 increased in UA-treated group. Importantly, UA decreased p-PERK, PERK, p-eIF2α, eIF2α, ATF4 and CHOP levels compared with control group.

Conclusion: Our results showed that UA treatment could improve the DCD liver transplantation likely through inhibiting apoptosis and PERK-CHOP pathway.

Keywords: Apoptosis; Cardiac death; Liver transplantation; Ursolic acid.

MeSH terms

  • Alanine Transaminase / blood
  • Animals
  • Apoptosis / drug effects*
  • Blood Vessels / metabolism
  • Blood Vessels / pathology
  • Female
  • Immunohistochemistry
  • Injections, Intraperitoneal
  • Liver / metabolism
  • Liver / pathology
  • Liver Transplantation*
  • Male
  • Malondialdehyde / analysis
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Signal Transduction
  • Swine
  • Swine, Miniature
  • Tissue Donors
  • Transcription Factor CHOP / metabolism
  • Triterpenes / pharmacology*
  • Ursolic Acid
  • bcl-2-Associated X Protein / metabolism
  • eIF-2 Kinase / metabolism

Substances

  • Proto-Oncogene Proteins c-bcl-2
  • Triterpenes
  • bcl-2-Associated X Protein
  • Transcription Factor CHOP
  • Malondialdehyde
  • Alanine Transaminase
  • PERK kinase
  • eIF-2 Kinase