Effect of α-amplexichromanol (27a) on lipid mediator formation in zymosan induced murine peritonitis

Neukirch, K. et al. Exploration of Long-Chain Vitamin E Metabolites for the Discovery of a Highly Potent, Orally Effective, and Metabolically Stable 5-LOX Inhibitor that Limits Inflammation. J Med Chem 64, 11496-11526 (2021). https://doi.org/10.1021/acs.jmedchem.1c00806

CD-1 mice received 27a or zileuton, with DMSO (2%) in saline (0.5 mL) as a vehicle for i.p. administration and carboxymethylcellulose (0.5%) in 10% Tween 20 (0.5 mL) as a vehicle for p.o. administration. Zymosan (2 mg/mL insaline, i.p., 0.5 mL, Sigma-Aldrich) was injected at 30 min (i.p.) or 60min (p.o.) post compound administration. Mice were sacrificed by inhalation of CO2 after another 30 min to determine LTC4 levels, lipid mediator profiles, metabolites, and vascular permeability and after 4 h to analyze LTB4 levels and cell infiltration. Plasma and peritoneal exudates were collected, and cells were counted in exudates after trypan blue staining. Compound 27a, its metabolites, and lipid mediators were extracted and analyzed by UPLC-MS/MS as described in Neukirch et al., 2021.