title: Succinate Accumulation and Ischemia-Reperfusion Injury: Of Mice but Not Men, a Study in Renal Ischemia-Reperfusion.
abstract: A recent seminal paper implicated ischemia-related succinate accumulation followed by succinate-driven reactive oxygen species formation as a key driver of ischemia-reperfusion injury. Although the data show that the mechanism is universal for all organs tested (kidney, liver, heart, and brain), a remaining question is to what extent these observations in mice translate to humans. We showed in this study that succinate accumulation is not a universal event during ischemia and does not occur during renal graft procurement; in fact, tissue succinate content progressively decreased with increasing graft ischemia time (p < 0.007). Contrasting responses were also found with respect to mitochondrial susceptibility toward ischemia and reperfusion, with rodent mitochondria robustly resistant toward warm ischemia but human and pig mitochondria highly susceptible to warm ischemia (p < 0.05). These observations suggest that succinate-driven reactive oxygen formation does not occur in the context of kidney transplantation. Moreover, absent allantoin release from the reperfused grafts suggests minimal oxidative stress during clinical reperfusion.
authors.affiliation: Department of Transplantation Surgery, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: L G M
authors.initials: LG
authors.lastname: Wijermars
authors.affiliation: Department of Transplantation Surgery, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: A F
authors.initials: AF
authors.lastname: Schaapherder
authors.affiliation: Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: S
authors.initials: S
authors.lastname: Kostidis
authors.affiliation: Department of Physiology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: R C I
authors.initials: RC
authors.lastname: Wüst
authors.affiliation: Department of Transplantation Surgery, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: J H
authors.initials: JH
authors.lastname: Lindeman
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000378:metabolism* / Q000473:pathology*; D019802:Succinic Acid / Q000378:metabolism*
chemical_list: D017382:Reactive Oxygen Species; D019802:Succinic Acid
keywords: animal models; ischemia reperfusion injury (IRI); kidney transplantation/nephrology; translational research/science