Luminal administration of biliverdin ameliorates ischemia-reperfusion injury following intestinal transplant in rats.

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.

• Authors: Tsuyoshi Nojima, Takafumi Obara, Hirotsugu Yamamoto, Tetsuya Yumoto, Takuro Igawa, Toshiyuki Aokage, Mizuki Seya, Atsunori Nakao, Hiromichi Naito
• Journal: Surgery (Surgery) Vol. 172 Issue 5 Pg. 1522-1528 (11 2022) ISSN: 1532-7361 [Electronic] United States
• PMID: 36088170 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.

Chemical References

• Chemokines
• Claudin-1
• Interleukin-6
• Nitric Oxide Synthase Type II
• Biliverdine

Topics

• Animals
• Biliverdine (metabolism)
• Chemokines (metabolism)
• Claudin-1 (metabolism)
• Interleukin-6 (metabolism)
• Nitric Oxide Synthase Type II (metabolism)
• Rats
• Rats, Inbred Lew
• Reperfusion Injury (etiology, metabolism, prevention & control)