H2S donor molecules against cold ischemia-reperfusion injury in preclinical models of solid organ transplantation
Loading...
Date
2021
Journal Title
Journal ISSN
Volume Title
Publisher
Pharmacological Research
Abstract
Cold ischemia-reperfusion injury (IRI) is an inevitable and unresolved problem that poses a great challenge in
solid organ transplantation (SOT). It represents a major factor that increases acute tubular necrosis, decreases
graft survival, and delays graft function. This complicates graft quality, post-transplant patient care and organ
transplantation outcomes, and therefore undermines the success of SOT. Herein, we review recent advances in
research regarding novel pharmacological strategies involving the use of different donor molecules of hydrogen
sulfide (H2S), the third established member of the gasotransmitter family, against cold IRI in different experimental
models of SOT (kidney, heart, lung, liver, pancreas and intestine). Additionally, we discuss the molecular
mechanisms underlying the effects of these H2S donor molecules in SOT, and suggestions for clinical translation.
Our reviewed findings showed that storage of donor organs in H2S-supplemented preservation solution or
administration of H2S to organ donor prior to organ procurement and to recipient at the start and during
reperfusion is a novel, simple and cost-effective pharmacological approach to minimize cold IRI, limit posttransplant
complications and improve transplantation outcomes. In conclusion, experimental evidence demonstrate
that H2S donors can significantly mitigate cold IRI during SOT through inhibition of a complex cascade of
interconnected cellular and molecular events involving microcirculatory disturbance and microvascular
dysfunction, mitochondrial injury, inflammatory responses, cell damage and cell death, and other damaging
molecular pathways while promoting protective pathways. Translating these promising findings from bench to
bedside will lay the foundation for the use of H2S donor molecules in clinical SOT in the future.
Description
Research Article
Keywords
Cold ischemia-reperfusion injury (IRI), Solid organ transplantation (SOT), Static cold storage (SCS), Hydrogen sulfide (H2S), H2S donor molecules