Compound 27a inhibits 5-LOX product
formation and
limits inflammation in murine peritonitis. (A) Time scale for zymosan-induced
murine peritonitis. (A–I) Mice received 27a (B–E,
I: 10 mg/kg; F, G: 30 mg/kg; H: 3 mg/kg; B–E: i.p.; F–I:
p.o.) or zileuton (zil; B–E: 10 mg/kg; F, G: 30 mg/kg; H: 3
mg/kg; B–E: i.p.; F–H: p.o.) and were killed 30 min
(B, C, F–I) or 4 h (D, E) post zymosan injection. (B, H) LTC4 levels in the exudate analyzed by ELISA. (C) Vascular permeability.
(D) LTB4 levels in the exudate analyzed by ELISA. (E) Immune
cell infiltration into the peritoneal cavity. (F, G) Concentration
of 27a in the plasma (F) and exudate (G). (I) Quantitative
illustration of the lipid mediator network in the peritoneal exudate
from mice given 27a as compared to the vehicle. The node
size represents the mean concentration in pg, and the color intensity
denotes the fold change for each lipid mediator. °LTC4 was analyzed by ELISA, and all other lipid mediators and fatty acids
were analyzed by UPLC-MS/MS. AA, arachidonic acid; DHA, docosahexaenoic
acid; EPA, eicosapentaenoic acid; LX, lipoxin; MaR, maresin; 20-OH-LTB4, 20-hydroxy-LTB4; PD, protectin; Rv, resolvin;
t-LTB4, LTB4 isomer; TX, thromboxane. Data are
expressed as mean (I) with single values (B–H) from n = 3 (F, w/o), n = 4 (C, 27a), n = 5 (C, w/o, F, 27a), n = 6 (B, C, zil, D, E), n = 8 (H, w/o), n = 9 (G, w/o, H, zil, I, w/o), and n =
10 (F, zil, G, 27a and zil, H, 27a, I, 27a) mice. Two-tailed unpaired t-test of
log data (B–H).