Evidence for simvastatin anti-inflammatory actions based on quantitative analyses of NETosis and other inflammation/oxidation markers

Publication date: 2014 Source:Results in Immunology, Volume 4 Author(s): Walid M. Al-Ghoul , Margarita S. Kim , Nadeem Fazal , Anser C. Azim , Ashraf Ali Simvastatin (SMV) has been shown to exhibit promising anti-inflammatory properties alongside its classic cholesterol lowering action. We tested these emerging effects in a major thermal injury mouse model (3rd degree scald, ∼20% TBSA) with previously documented, inflammation-mediated intestinal defects. Neutrophil extracellular traps (NETs) inflammation measurement methods were used alongside classic gut mucosa inflammation and leakiness measurements with exogenous melatonin treatment as a positive control. Our hypothesis is that simvastatin has protective therapeutic effects against early postburn gut mucosa inflammation and leakiness. To test this hypothesis, we compared untreated thermal injury (TI) adult male mice with TI littermates treated with simvastatin (0.2 mg/kg i.p., TI + SMV) immediately following burn injury and two hours before being sacrificed the day after; melatonin-treated (Mel) (1.86 mg/kg i.p., TI + Mel) mice were compared as a positive control. Mice were assessed for the following: (1) tissue oxidation and neutrophil infiltration in terminal ileum mucosa using classic carbonyl, Gr-1, and myeloperoxidase immunohistochemical or biochemical assays, (2) NETosis in terminal ileum and colon mucosa homogenates and peritoneal and fluid blood samples utilizing flow cytometric analyses of the sur...
Source: Results in Immunology - Category: Allergy & Immunology Source Type: research