BAY 11-7082, a nuclear factor-κB inhibitor, reduces inflammation and apoptosis in a rat cardiac ischemia-reperfusion injury model.

Abstract

Despite development of therapeutic modalities, myocardial ischemia-reperfusion (I/R) injury remains an important cause of cardiac dysfunction. Multiple strategies exist experimentally, but few are clinically available. Nuclear factor kappa-B (NF-κB) is a key transcription factor in the inflammatory response and is implicated in I/R injury. We hypothesized that the NFκB inhibitor BAY 11-7082 (BAY) would decrease the extent of injury after myocardial I/R. Hypoxia-reoxygenation (H/R) was induced in rat neonatal cardiomyocytes with or without BAY pretreatment. NF-κB activation, vascular cell adhesion molecule (VCAM)-1, and monocyte chemoattractant protein (MCP)-1 were assayed by immunocytochemistry, Western blot or reverse transcriptase-polymerase chain reaction (RT-PCR). Sprague-Dawley rats (n = 7) were administered BAY (130 µg/kg) and I/R was induced by ligation of the left anterior descending artery (LAD) for 30 minutes followed by reperfusion. Infarct size was analyzed after 24 hours. At 2 weeks, echocardiography was performed to evaluate ventricular function and hearts were analyzed for fibrosis and apoptosis. BAY treatment inhibited NF-κB p65 activation, as well as VCAM-1 and MCP-1 expression induced by H/R in cardiomyocytes. Compared with control rats, BAY pretreated rats showed reduced infarct size. Echocardiograms demonstrated preserved systolic function as a fractional shortening in the BAY+I/R group (P < 0.05). Fibrosis was reduced in the BAY+I/R group (P < 0.05) and apoptosis was also reduced in the BAY+I/R group (P < 0.05).In the rat myocardial I/R injury model, BAY significantly reduced the infarct size, and preserved myocardial function. These data demonstrate that a currently available and well-tolerated inhibitor of NF-κB can decrease the risk of myocardial injury associated with I/R.

• Authors: Yong Sook Kim, Ji Su Kim, Jin Sook Kwon, Myung Ho Jeong, Jeong Gwan Cho, Jong Chun Park, Jung Chaee Kang, Youngkeun Ahn
• Journal: International heart journal (Int Heart J) Vol. 51 Issue 5 Pg. 348-53 ( 2010) ISSN: 1349-3299 [Electronic] Japan
• PMID: 20966608 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 3-(4-methylphenylsulfonyl)-2-propenenitrile
• Chemokine CCL2
• NF-kappa B
• Nitriles
• Sulfones

Topics

• Animals
• Apoptosis (drug effects)
• Blotting, Western
• Cells, Cultured
• Chemokine CCL2 (blood)
• Disease Models, Animal
• Immunohistochemistry
• Inflammation (prevention & control)
• Myocytes, Cardiac (drug effects)
• NF-kappa B (antagonists & inhibitors)
• Nitriles (pharmacology, therapeutic use)
• Rats
• Rats, Sprague-Dawley
• Reperfusion Injury (physiopathology, prevention & control)
• Sulfones (pharmacology, therapeutic use)