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 12-O-tetradecanoylphorbol-13-acetate (TPA) (0.2-2.5 nmol/mouse) induced a dose-related increase in vascular permeability, which was determined by pontamine sky blue exudation into 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 mumol/mouse). 2,3,5-trimethyl-6-(12-hydroxy-5,10-dodecadiynyl)-1,4-benzoquinone (AA861) (10 mumol/mouse) and quercetin (3 mumol/mouse) significantly inhibited the TPA-induced dye exudation. However, indomethacin (250-1000 nmol/mouse) tended to inhibit the TPA-induced dye exudation, but the inhibition was not statistically significant. Treatment with AA861 (10 mumol/mouse) also caused a marked inhibition of TPA-induced neutrophil infiltration. Quercetin, NDGA and AA861 inhibited epidermal lipoxygenase activity, but indomethacin failed to inhibit it. On the other hand, indomethacin inhibited epidermal cyclooxygenase, but quercetin, 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.