A Novel Oxygen Carrier (M101) Attenuates Ischemia-Reperfusion Injuries during Static Cold Storage in Steatotic Livers

Int J Mol Sci. 2021 Aug 9;22(16):8542. doi: 10.3390/ijms22168542.

Abstract

The combined impact of an increasing demand for liver transplantation and a growing incidence of nonalcoholic liver disease has provided the impetus for the development of innovative strategies to preserve steatotic livers. A natural oxygen carrier, HEMO2life®, which contains M101 that is extracted from a marine invertebrate, has been used for static cold storage (SCS) and has shown superior results in organ preservation. A total of 36 livers were procured from obese Zucker rats and randomly divided into three groups, i.e., control, SCS-24H and SCS-24H + M101 (M101 at 1 g/L), mimicking the gold standard of organ preservation. Ex situ machine perfusion for 2 h was used to evaluate the quality of the livers. Perfusates were sampled for functional assessment, biochemical analysis and subsequent biopsies were performed for assessment of ischemia-reperfusion markers. Transaminases, GDH and lactate levels at the end of reperfusion were significantly lower in the group preserved with M101 (p < 0.05). Protection from reactive oxygen species (low MDA and higher production of NO2-NO3) and less inflammation (HMGB1) were also observed in this group (p < 0.05). Bcl-1 and caspase-3 were higher in the SCS-24H group (p < 0.05) and presented more histological damage than those preserved with HEMO2life®. These data demonstrate, for the first time, that the addition of HEMO2life® to the preservation solution significantly protects steatotic livers during SCS by decreasing reperfusion injury and improving graft function.

Keywords: ischemia-reperfusion; oxygen-carrier; steatotic livers.

MeSH terms

  • Animals
  • Caspase 3 / metabolism
  • Cyclin D1 / metabolism
  • Fatty Liver / metabolism*
  • Fatty Liver / pathology
  • HMGB1 Protein / metabolism
  • Hemoglobins / pharmacology*
  • Lactic Acid / metabolism
  • Liver / metabolism*
  • Male
  • Rats
  • Rats, Zucker
  • Reperfusion Injury / metabolism
  • Reperfusion Injury / pathology
  • Reperfusion Injury / prevention & control*
  • Transaminases / metabolism

Substances

  • HMGB1 Protein
  • Hbp1 protein, rat
  • Hemoglobins
  • hemoglobin M101
  • Cyclin D1
  • Lactic Acid
  • Transaminases
  • Casp3 protein, rat
  • Caspase 3