H2S donor molecules against cold ischemia-reperfusion injury in preclinical models of solid organ transplantation

George J Dugbartey; Smriti Juriasingani; Max Y Zhang; Alp Sener

doi:10.1016/j.phrs.2021.105842

H₂S donor molecules against cold ischemia-reperfusion injury in preclinical models of solid organ transplantation

Pharmacol Res. 2021 Oct:172:105842. doi: 10.1016/j.phrs.2021.105842. Epub 2021 Aug 24.

Authors

George J Dugbartey¹, Smriti Juriasingani², Max Y Zhang³, Alp Sener⁴

Affiliations

¹ Department of Surgery, Division of Urology, London Health Sciences Center, Western University, London, Ontario, Canada; Matthew Mailing Center for Translational Transplant Studies, London Health Sciences Center, Western University, London, Ontario, Canada; Multi-Organ Transplant Program, Western University, London Health Sciences Center, Western University, London, Ontario, Canada; Department of Pharmacology and Toxicology, School of Pharmacy, College of Health Sciences, University of Ghana, Legon, Accra, Ghana.
² Department of Surgery, Division of Urology, London Health Sciences Center, Western University, London, Ontario, Canada; Matthew Mailing Center for Translational Transplant Studies, London Health Sciences Center, Western University, London, Ontario, Canada.
³ Matthew Mailing Center for Translational Transplant Studies, London Health Sciences Center, Western University, London, Ontario, Canada; Multi-Organ Transplant Program, Western University, London Health Sciences Center, Western University, London, Ontario, Canada.
⁴ Department of Surgery, Division of Urology, London Health Sciences Center, Western University, London, Ontario, Canada; Matthew Mailing Center for Translational Transplant Studies, London Health Sciences Center, Western University, London, Ontario, Canada; Multi-Organ Transplant Program, Western University, London Health Sciences Center, Western University, London, Ontario, Canada; Department of Microbiology & Immunology, Schulich School of Medicine & Dentistry, University of Western Ontario, London, Ontario, Canada. Electronic address: Alp.Sener@lhsc.on.ca.

PMID: 34450311
DOI: 10.1016/j.phrs.2021.105842

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 post-transplant 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.

Keywords: Cold ischemia-reperfusion injury (IRI); H(2)S donor molecules; Hydrogen sulfide (H(2)S); Solid organ transplantation (SOT); Static cold storage (SCS).

Publication types

Review

MeSH terms

Animals
Cold Ischemia*
Humans
Hydrogen Sulfide / metabolism*
Models, Animal
Organ Transplantation*
Reperfusion Injury / drug therapy*
Reperfusion Injury / metabolism

Substances

Hydrogen Sulfide