Effects of AGI-1096, a novel antioxidant compound with anti-inflammatory and antiproliferative properties, on rodent allograft arteriosclerosis

Transplantation
Seiichiro MurataRobert C Robbins

Abstract

AGI-1096 is a novel phenolic intracellular antioxidant with anti-inflammatory and antiproliferative properties. In vitro, AGI-1096 inhibited the inducible expression of vascular cell adhesion molecule (VCAM)-1, E-selectin, and monocyte chemoattractant protein (MCP)-1 in endothelial cells and tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta secretion from lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cells. It also inhibited serum-stimulated proliferation of aortic smooth-muscle cells. In vivo, AGI-1096 demonstrated anti-inflammatory properties in a murine delayed-type hypersensitivity model. Given these antioxidant, anti-inflammatory and antiproliferative properties, we reasoned that AGI-1096 may be able to prevent chronic allograft arteriosclerosis. This hypothesis was tested in a rodent aortic transplantation model. Donor descending aortas from August-Copenhagen-Irish rats were heterotopically transplanted into Lewis rat abdomens in end-to-end fashion. Animals were assigned to six groups as follows: AGI-1096 0 mg/kg per day (vehicle, n = 10), 10 mg/kg per day (n = 10), 20 mg/kg per day (n = 10), 40 mg/kg per day (n = 10), positive control (cyclosporine A 10 mg/kg per day by oral gavage, n = 10),...Continue Reading

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Citations

Nov 18, 2006·Expert Opinion on Pharmacotherapy·Javier SegoviaLuis Alonso-Pulpón
May 15, 2012·Catheterization and Cardiovascular Interventions : Official Journal of the Society for Cardiac Angiography & Interventions·Jonathan WattKeith G Oldroyd
Sep 30, 2016·Platelets·Stephanie A HoustonSimon Kennedy
Apr 25, 2007·Autoimmunity·Guangwei LiuYong Zhao

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