Inhibition of 5-Lipoxygenase Pathway Attenuates Acute Liver Failure by Inhibiting Macrophage Activation
Figure 4
AA-861 significantly decreased total hepatic 5-LO protein and mRNA expression in D-GalN/LPS-treated animals. (a) Representative western blot analysis of the total 5-LO protein expression in liver samples 24 hr after D-GalN/LPS treatment in animals receiving placebo or AA-861. (b) AA-861 significantly abrogated the increased number of 5-LO-positive cells in the liver from D-GalN/LPS-treated rats. Representative photomicrographs (400x) of liver sections immunostained with 5-LO antibody 24 hr after D-GalN/LPS-treated rats received placebo (left panels) or AA-861 (right panels). (c) Representative RT-PCR analysis of 5-LO mRNA expression in liver samples 8 hr after D-GalN/LPS treatment in animals receiving placebo or AA-861. (d) AA-861 significantly reduced LTB4 levels in liver from D-GalN/LPS-treated rats. Liver tissue was obtained 24 hr after D-GalN/LPS treatment from animals receiving placebo or AA-861. Samples were homogenized and extracted in C18-silica, reverse-phase cartridges, and LTB4 was determined by highly specific enzyme immunoassay. Results represent the mean ± standard error.
