Protective effects of deferoxamine mesylate preconditioning on pancreatic tissue in orthotopic liver autotransplantation in rats.

Abstract

BACKGROUND:

Deferoxamine mesylate is known to ameliorate tissue ischemia-reperfusion injury. This study was designed to explore the impact of deferoxamine mesylate preconditioning (DMP) on pancreatic tissue and its possible effects during orthotopic liver autotransplantation.

METHODS:

A modified orthotopic liver autotransplantation model was used to simulate pancreatic ischemia-reperfusion injury. Sprague-Dawley rats (0.25-0.30 kg) were randomly divided into normal control, autotransplantation (AT), systemic deferoxamine mesylate preconditioning (SDMP), and partial deferoxamine mesylate conditioning (PDMC) groups. The SDMP group was injected with deferoxamine mesylate (75-90 mg; 300 mg/kg), via the celiac artery at 24 and 48 hours before surgery. During surgery, the PDMC group underwent liver perfusion by means of deferoxamine mesylate solution (20 ml; 0.6 mmol/L) rather than Ringer's lactate solution, with no prior preconditioning. At 6, 24, and 48 hours after surgery, the rats were sacrificed to sample their pancreatic tissues for the expression of hypoxia-inducible factor-1α (HIF-1α) and malondialdehyde (MDA) content. The samples were subjected to blood chemistry analyses, light and transmission electron microscopic morphological studies, and quantitative measurement of HIF-1α expression.

RESULTS:

The serum levels of amylase, lipase, and MDA in SDMP and PDMC groups were significantly lower than those in the AT group at 6, 24, and 48 hours after orthotopic liver autotransplantation (P < .05). Light and electron microscopic analyses showed much more severe pancreatic injury in the autotransplantation than in the SDMP and PDMC groups. The HIF-1α expression was increased in the SDMP and PDMC groups more than in the autotransplantation group (P < .05).

CONCLUSIONS:

Deferoxamine mesylate preconditioning protected pancreatic tissue in orthotopic liver autotransplantation in rats. Inhibition of oxidative toxic reactions and up-regulated expression of HIF-1α protein are possible mechanisms.

• Authors: Y Li, P-J Zhang, C Jin, B Zhou, X-Y Liu, L-D Tao, M Feng
• Journal: Transplantation proceedings (Transplant Proc) Vol. 43 Issue 5 Pg. 1450-5 (Jun 2011) ISSN: 1873-2623 [Electronic] United States
• PMID: 21693216 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Inc. All rights reserved.

Chemical References

• HIF1A protein, human
• Hypoxia-Inducible Factor 1, alpha Subunit
• Malondialdehyde
• Lipase
• Amylases
• Deferoxamine

Topics

• Amylases (blood)
• Animals
• Deferoxamine (administration & dosage)
• Hypoxia-Inducible Factor 1, alpha Subunit (metabolism)
• Immunohistochemistry
• Lipase (blood)
• Liver Transplantation
• Malondialdehyde (metabolism)
• Microscopy
• Pancreas (blood supply, metabolism)
• Rats
• Rats, Sprague-Dawley
• Reperfusion Injury