Luminal administration of biliverdin ameliorates ischemia-reperfusion injury following intestinal transplant in rats.
Surgery
; 172(5): 1522-1528, 2022 11.
Article
em En
| MEDLINE
| ID: mdl-36088170
ABSTRACT
BACKGROUND:
Intestinal grafts are susceptible to ischemia-reperfusion injury, resulting in the loss of mucosal barrier function and graft failure. Biliverdin is known to exert a variety of cytoprotective functions against oxidative tissue injury. Because the mucosal layer is the primary site of ischemia-reperfusion injury, mucosa-targeting strategies by luminal delivery of reagents might be beneficial. We tested whether intraluminal administration of biliverdin as an adjuvant to standard preservation solutions protected against ischemia-reperfusion injury.METHODS:
Orthotopic syngeneic intestinal transplants were performed on Lewis rats after 6 hours of cold preservation. Saline containing biliverdin (10 µM) or without biliverdin was introduced into the lumen of the intestinal grafts immediately before cold preservation.RESULTS:
Damage to the intestinal mucosa caused by ischemia-reperfusion injury resulted in severe morphological changes, including blunting of the villi and erosion, and led to significant loss of gut barrier function 3 hours after reperfusion. These changes to the mucosa were notably ameliorated by intraluminal administration of biliverdin. Biliverdin also effectively inhibited upregulation of messenger RNAs for interleukin-6, inducible nitric oxide synthase, and C-C motif chemokine 2. Additionally, biliverdin treatment prevented the loss of expression of claudin-1, a transmembrane, tight-junction barrier protein. The 14-day survival of recipients of biliverdin-treated grafts was significantly improved as compared with the recipients of saline-treated control grafts (83.3% vs 38.9%, P = .030).CONCLUSION:
This study demonstrated that luminally delivered biliverdin provides beneficial effects during the transplant of rat small intestinal grafts and could be an attractive therapeutic option in organ transplantation.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Biliverdina
/
Traumatismo por Reperfusão
Tipo de estudo:
Etiology_studies
Limite:
Animals
Idioma:
En
Revista:
Surgery
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Japão