The Protective Effect of Glucosamine on Cardiac Function Following Trauma Hemorrhage: Downregulation of cardiac NF-KB signaling.

Administration of glucosamine (GlcN) following trauma-hemorrhage (TH) increased tissue levels of O-linked N-acetylglucosamine (GlcNAc) attenuated circulating proinflammatory cytokines TNF-ct and 1L-6, and improved cardiac function. However, the mechanism(s) by which increased O-GlcNAc levels improve recovery and decrease the inflammatory response is unclear. Therefore, the goal of this study was to determine if the beneficial effect of GlcN was mediated by downregulation of NF-KB signaling pathway following TH. Fasted male rats were subject to TH by bleeding to a mean arterial blood pressure of 40 mmHg for 90 minutes followed by 60 minutes resuscitation; GleN (2.5mls, 150mM) or vehicle (2.5mls normal saline) were administered mid-way through resuscitation. Two hours later mean arterial pressure, heart rate and ±dp/dt were recorded and tissues harvested. Consistent with our earlier study GlcN improved cardiac function at the end of resuscitation. In hearts from vehicle treated rats, there were increased levels of intercellular adhesion molecule 1 protein ICAM 1), IκB-α phosphorylation, nuclear NF-KB protein and increased NF-κB nuclear DNA binding activity compared to sham controls. GlcN treatment significantly decreased ICAMI expression, IκB-α phosphorylation, nuclear NF-κB expression and NF-KB DNA binding activity. Thus, GleN administration during resuscitation attenuated NFKB signaling pathway in the heart and this may contribute to the protection associated with increased protein O-GlcNAc levels. [ABSTRACT FROM AUTHOR]