Novel Pharmacologic Strategies to Protect the Liver from Ischemia- Reperfusion Injury
Matias A. Avila, Maria Iniguez, Javier Dotor, Esperanza Feijoo, Saioa Goni, Jesus Prieto and Carmen Berasain
Affiliation: Division of Hepatology and Gene Therapy, CIMA. University of Navarra, Avda. Pio XII, n55, 31008 Pamplona, Spain.
Ischemia and reperfusion (I/R) injury develops when blood flow is interrupted for a long period of time and then restarted. In the liver, this type of damage occurs in clinical settings such as liver transplantation and hepatic resection. Given the shortage of donor organs it is essential to maximize the use of sub-optimal organs, those previously rejected due to elevated risk of malfunction, and to increase split-liver transplantation interventions. Therefore, the development of strategies that preserve organ viability and promote liver regeneration is urgently needed. As observed for other organs, a brief period of ischemia followed by short reperfusion before the surgical procedure significantly increases liver resistance towards prolonged periods of ischemia. This phenomenon is known as ischemic preconditioning, and is the only protective strategy that has reached clinical practice. Recently, intensive research has improved our understanding of the mechanisms involved in I/R liver injury, and the biologic bases of ischemic preconditioning. This knowledge has generated relevant patented advances in the field, including the targeted inhibition of pro-apoptotic pathways, the interference with neutrophil activation, and the identification of cytoprotective cytokines. Here, we briefly review the mechanisms of hepatic ischemic damage, and present the most promising pharmacologic approaches against I/R injury. This article also includes recent patents on this topic.
Keywords: Liver, ischemia/reperfusion injury, antioxidants, tumor necrosis factor alpha, cytoprotective cytokines, growth factors, nitric oxide, adenosine, apoptosis inhibitors
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