Jia-bo Wang,Trisha Dezube, Margaret M. Kearney, Krishne MacLean*
Abstract
Sepsis is characterized by up-regulation of inflammatory mediators in different pathways. Phosphodiesterase enzymes are often targets for many pharmacological inhibitions which can prolong or activate the effects of physiological processes that mediated by cAMP or cGMP through inhibition of their degradation. We hypothesized that Pentoxifylline (PTX) treatment in sepsis model down-regulates the inflammatory response and may decrease liver injury. Wild type mice were randomized into three groups: Sham, LPS (5 mg/kg i.v.), and PTX + LPS (25 mg/kg i.v., injection). Following 4-hour of endotoxemia, we analysis plasma for liver enzymes, liver tissue for histology (H&E) and immunohistochemistry, in addition to evaluated intercellular adhesion molecule 1 (ICAM-1) by electrophoretic mobility shift assay. Pentoxifylline (PTX) has been shown to down-regulated both ICAM-1 and pro-inflammatroy cytokine effects on lipopolysaccharide (LPS) induced liver injury. Further studies of endotoxemia are needed to ascertain the benefit of PTX as liver protection agent.
Keywords: Phosphodiesterase; Sepsis; LPS; Pentoxifylline
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