INHIBITORY EFFECTS OF SULFONATED SHALE OILS (AMMONIUM BITUMINOSULPHONATES, ICHTHYOLS) ON ENZYMES OF POLYENOIC FATTY-ACID METABOLISM

The two commercial pharmaceutical preparations of ammonium bituminosul phonates, Leukichthol and Dark Ichthyol, were shown to inhibit the for mation of 5S-hydroxy-6E,8Z,11Z,14Z-eicosatetraenoic acid (5-HETE) from external arachidonic acid by human polymorphonuclear leukocytes stimu lated by ionophore A-23187 in a dose-dependent manner. Pure arachidona te 15-lipoxygenases from rabbit reticulocytes and soya beans, and the particulate prostaglandin endoperoxide synthase from sheep vesicular g lands, were also inhibited. With the reticulocyte lipoxygenase, the Ic hthyols suppressed the enzyme activity by two different mechanisms: (1 ) a prolongation of the lag period typical of lipoxygenase catalysis, and (2) by a lowering of the maximal enzymatic activity after the end of lag period. As expected, the first effect was reversed by the addit ion of the lipoxygenase product 13S-hydroperoxy-9Z,11E-octadecadienoic acid (13-HpODE). Ammonium bituminosulphonates are thus universal inhi bitors of lipoxygenase activities, and the latter are of potential imp ortance in inflammatory dermatoses.