Pretreatment with bone morphogenetic protein-7 (BMP-7) mimics ischemia preconditioning following intestinal ischemia/reperfusion injury in the intestine and liver

Ravi Radhakrishnan, Geetha Radhakrishnan, Hari R. Radhakrishnan, Hasen Xue, Sasha D. Adams, Stacey D. Moore-Olufemi, Matthew T. Harting, Charles S. Cox, Bruce C. Kone

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Intestinal ischemia/reperfusion (I/R) injury has been shown to cause intestinal mucosal injury and adversely affect function. Ischemic preconditioning (IPC) has been shown to protect against intestinal I/R injury by reducing polymorphonuclear leukocyte infiltration, intestinal mucosal injury, and liver injury, and preserve intestinal transit. Bone morphogenetic protein 7 (BMP-7) has been shown to protect against I/R injury in the kidney and brain. Recently, microarray analysis has been used to examine the possible IPC candidate pathways. This work revealed that IPC may work through upregulation of BMP-7. The purpose of this study was to examine if pretreatment with BMP-7 would replicate the effects seen with IPC in the intestine and liver after intestinal I/R. Rats were randomized to six groups: sham, I/R (30 min of superior mesenteric artery occlusion and 6 h of R), IPC+R (three cycles of superior mesenteric artery occlusion for 4 min and R for 10 min), IPC+I/R, BMP-7+R (100 μm/kg recombinant human BMP-7), or BMP-7+I/R. A duodenal catheter was placed, and 30 min before sacrifice, fluorescein isothiocyanate-Dextran was injected. At sacrifice, dye concentrations were measured to determine intestinal transit. Ileal mucosal injury was determined by histology and myeloperoxidase activity was used as a marker of polymorphonuclear leukocyte infiltration. Serum levels of aspartate aminotransferase were measured at sacrifice to determine liver injury. Pretreatment with BMP-7 significantly improved intestinal transit and significantly decreased intestinal mucosal injury and serum aspartate aminotransferase levels, comparable to animals undergoing IPC. In conclusion, BMP-7 protected against intestinal I/R-induced intestinal and liver injury. Bone morphogenetic protein 7 may be a more logical surrogate to IPC in the prevention of injury in the setting of intestinal I/R.

Original languageEnglish (US)
Pages (from-to)532-536
Number of pages5
JournalShock
Volume30
Issue number5
DOIs
StatePublished - Nov 2008
Externally publishedYes

Fingerprint

Bone Morphogenetic Protein 7
Ischemic Preconditioning
Reperfusion Injury
Intestines
Ischemia
Liver
Wounds and Injuries
Reperfusion
Superior Mesenteric Artery
Aspartate Aminotransferases
Neutrophils
Microarray Analysis
Serum
Peroxidase
Histology
Coloring Agents
Up-Regulation
Catheters
Kidney

Keywords

  • BMP-7
  • Ileus
  • Intestinal transit
  • Ischemia/reperfusion

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine
  • Emergency Medicine

Cite this

Pretreatment with bone morphogenetic protein-7 (BMP-7) mimics ischemia preconditioning following intestinal ischemia/reperfusion injury in the intestine and liver. / Radhakrishnan, Ravi; Radhakrishnan, Geetha; Radhakrishnan, Hari R.; Xue, Hasen; Adams, Sasha D.; Moore-Olufemi, Stacey D.; Harting, Matthew T.; Cox, Charles S.; Kone, Bruce C.

In: Shock, Vol. 30, No. 5, 11.2008, p. 532-536.

Research output: Contribution to journalArticle

Radhakrishnan, Ravi ; Radhakrishnan, Geetha ; Radhakrishnan, Hari R. ; Xue, Hasen ; Adams, Sasha D. ; Moore-Olufemi, Stacey D. ; Harting, Matthew T. ; Cox, Charles S. ; Kone, Bruce C. / Pretreatment with bone morphogenetic protein-7 (BMP-7) mimics ischemia preconditioning following intestinal ischemia/reperfusion injury in the intestine and liver. In: Shock. 2008 ; Vol. 30, No. 5. pp. 532-536.
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