Ischemia reperfusion (I/R) injury occurs when hypoxic organ damage is exacerbated following the return of blood flow and oxygen delivery, and is a major concern during solid organ transplantation, trauma, hypovolemic shock, and elective liver insection, when inflow occlusion or vascular exclusion is used to minimize blood loss. Liver I/R injury includes both direct cellular damage due to ischemic insult as well as dysfunction and damage resulting from inflammatory pathways activated by the new inflow. Pitt researchers are exploring the use of the nuclear factor high mobility group box 1 (HMGB1) for its uses is doing just this.
Description
HMGB1 typically serves as a late mediator of lethality in sepsis as well as following necrotic, but not apoptotic, cell death. In contrast to its usual proinflammatory role, researchers have discovered that preconditioning with low doses of HMGB1 results in protection from inflammation and organ injury following hepatic I/R. Pretreatment of mice with HMGB1 significantly decreased liver damage after I/R and also resulted in markedly lower serum TNF and IL-6 compared to controls. Use of HMGB1 as a preconditioning agent is a promising strategy in decreasing organ damage in cases of ischemic injury.
Applications
· Minimizing organ damage in cases of ischemic injury
· Potential uses in other clinical settings associated with inflammation and cellular necrosis caused by ischemic insults
Advantages
· Effective at low doses
· Primes cells with defense mechanisms that can prevent subsequent lethal injury
Invention Readiness
In vivo data available.
IP Status
https://patents.google.com/patent/US7829097B2
