We investigated the effects of raxofelast, a lipid peroxidation inhibitor, in an experimental model of burn wounds. C57BL/6 male mice of 25-30 g were immersed in 80 degrees C water for 10 seconds to achieve a partial-thickness scald burn. Animals received intraperitoneally either raxofelast (20 mg/kg/day for 14 days in 100 mu L) or its vehicle alone (100 mu L/day for 14 days). On day 14, burn areas were used for measuring conjugated dienes, reduced glutathione levels, histological damage, neoangiogenesis by immunohistochemistry and expression (Western blot) of the specific endothelial marker CD31 as well as quantification of microvessel density, VEGF wound content, endothelial and inducible nitric oxide synthase (eNOS and NOS) expression and wound nitrite content. Raxofelast decreased tissue conjugated dienes (vehicle 6.1 +/- 1.4 Delta ABS/mg protein; raxofelast 3.7 +/- 0.8 AABS/mg protein), prevented tissue glutathione consumption (vehicle 3.2 +/- 0.9 mu mol/g protein; raxofelast 6.7 +/- 1.8 mu mol/g protein), increased epithelial proliferation, extracellular matrix maturation, and augmented neoangiogenesis as suggested by the marked increase in microvessel density and by the robust expression of the specific endothelial marker CD31 (vehicle 9.4 +/- 1.1 integrated intensity; raxofelast 14.8 +/- 1.8 integrated intensity). Furthermore, raxofelast enhanced VEGF wound content (vehicle 1.4 +/- 0.4 pg/mg protein; raxofelast 2.4 +/- 0.6 pg/mg protein), caused a marked expression of eNOS (vehicle 16.1 +/- 3 integrated intensity; raxofelast 26.2 +/- 4 integrated intensity) and NOS (vehicle 9.1 +/- 1.8 integrated intensity; raxofelast 16.2 +/- 3.5 integrated intensity) and increased wound nitrite content. Lipid peroxidation inhibition by raxofelast may be an effective therapeutic approach to improve clinical outcomes after thermal injury.
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|Titolo:||Lipid peroxidation inhibition by raxofelast improves angiogenesis and wound healing in experimental burn wounds|
|Data di pubblicazione:||2005|
|Appare nella tipologia:||01a Articolo in rivista|