Biliverdin protects against liver ischemia reperfusion injury in swine.
Ischemia reperfusion injury (IRI) in organ transplantation remains a serious and unsolved problem. Organs that undergo significant damage during IRI, function less well immediately after reperfusion and tend to have more problems at later times when rejection can occur. Biliverdin has emerged as an agent that potently suppress IRI in rodent models. Since the use of biliverdin is being developed as a potential therapeutic modality for humans, we tested the efficacy for its effects on IRI of the liver in swine, an accepted and relevant pre-clinical animal model. Administration of biliverdin resulted in rapid appearance of bilirubin in the serum and significantly suppressed IRI-induced liver dysfunction as measured by multiple parameters including urea and ammonia clearance, neutrophil infiltration and tissue histopathology including hepatocyte cell death. Taken together, our findings, in a large animal model, provide strong support for the continued evaluation of biliverdin as a potential therapeutic in the clinical setting of transplantation of the liver and perhaps other organs.
Centre of Biotechnologies, Antonio Cardarelli Hospital, Naples, Italy.
Barbara
B
Andria
Adele
A
Bracco
Chiara
C
Attanasio
Sigismondo
S
Castaldo
Maria Grazia
MG
Cerrito
Santolo
S
Cozzolino
Daniele
D
Di Napoli
Roberto
R
Giovannoni
Antonio
A
Mancini
Antonino
A
Musumeci
Ernesto
E
Mezza
Mario
M
Nasti
Vincenzo
V
Scuderi
Stefania
S
Staibano
Marialuisa
M
Lavitrano
Leo E
LE
Otterbein
Fulvio
F
Calise
D000818:Animals; D001664:Biliverdine / Q000627:therapeutic use*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D015427:Reperfusion Injury / Q000188:drug therapy*; D013552:Swine
D001664:Biliverdine