ADD10 protects renal cells from cold injuries by improving energy metabolism

Biochem Biophys Res Commun. 2022 Dec 17:634:62-69. doi: 10.1016/j.bbrc.2022.10.009. Epub 2022 Oct 4.

Abstract

Static cold storage (SCS) is currently the most widely used method for organ preservation, but a number of limitations are associated including tissue damage and restricted opportunity for organ repair. Thus, the development of improved hypothermic storage solutions is an urgent need. Herein, using a renal epithelial cell model (LLC-PK1), we tested the benefits of ADD10, a novel clinical grade antioxidant product, in reducing damages associated with ischemia-reperfusion (IR). Cells were stored up to 24h at 4 °C in University of Wisconsin (UW) solution without or in the presence of 1% ADD10 with following reperfusion up to 24h at 37 °C. The presence of ADD10 significantly decreased cells damages, cell death, and the level of reactive oxygen species (ROS) (P < 0.05). Concomitantly, ADD10 supplementation also favored an increased oxygen consumption rate (OCR) and improved bioenergetics of LLC-PK1 cells (P < 0.05). Finally, preliminary in vivo studies suggested a benefit of ADD10 on the renal function post-transplantation. In conclusion, these results demonstrate that the addition of ADD10 to the preservation solution not only efficiently protects renal cells during SCS, but also improves the functionality of cold-stored organs during transplantation.

Keywords: Antioxidative compound; Ischemia-reperfusion injury; Kidneys; Organs; Preservation; Static cold storage; Transplantation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allopurinol
  • Animals
  • Cold Injury*
  • Cold Temperature
  • Energy Metabolism
  • Glutathione
  • Humans
  • Insulin
  • Kidney / physiology
  • Kidney Transplantation*
  • LLC-PK1 Cells
  • Organ Preservation Solutions* / pharmacology
  • Reperfusion Injury* / prevention & control
  • Swine

Substances

  • Organ Preservation Solutions
  • Insulin
  • Glutathione
  • Allopurinol