Inhibition of 12-O-Tetradecanoylphorbol-13-Acetate-Induced Increase in Vascular Permeability in Mouse Skin by Lipoxygenase Inhibitors

The painting of mouse dorsal skin with 1 2-0-tetradecanoylphorbol-l3-acetate (TPA) (0.2-2.5 nrTiol/mouse) induced a dose-related increase in vascular permeability, which was determined by pontamine sky blue exudation mto the skin 5 hr after the TPA treatment. Marked infiltration of neutrophils in the dermal interstitium was also observed 5 hr after TPA treatment. Treatment of mice with nordihydroguaiaretic acid (NDGA) (10 µmol/mouse), 2,3,5-trimethyl-6-(12-hydroxy-5,1 0-dodecadiynyl)-1,4-benzoquinone (AA861) (10 µmol/mouse) and quercetm (3µmol/mouse) significantly inhibited the TPA-mduced dye exudation. However, indomethacin (250-1000µmol/mouse) tended to inhibit the TPA-mduced dye exudation, but the inhibition was not statistically significant. Treatment with AA861 (10µmol/mouse) also caused a marked inhibition of TPA-mduced neutrophil infiltration. Quercetm, NDGA and AA861 inhibited epidermal lipoxygenase activity, but indomethacin failed to inhibit it. On the other hand, indomethacin inhibited epidermal cyclooxygenase, but quercetm, NDGA and AA861 failed to inhibit it. The present study suggests involvement of a lipoxygenase product(s) in the mechanism of the TPA-induced increase in vascular permeability in the dorsal skin of mice.