Inhibitory effects of divalent metal ions on liver microsomal 7-ethoxyresorufin O-deethylase (EROD) activity of leaping mullet

The purpose of the present study was to elucidate in vitro effects of Hg2+, Zn2+, Ni2+ and Cd2+ on cytochrome P4501A1 (CYP1A1) dependent EROD activities in leaping mullet liver microsomes. Fish captured from the most polluted part of Izmir Bay, had highly elevated EROD activities, and induced CYP1A1 protein levels as determined by Western blotting. Although all of the metal ions caused inhibition of the initial velocity of the reaction, Hg2+ and Cd2+ exhibited much higher inhibitory effect at lower concentrations and they were evidently more potent inhibitors than others. The inhibitor concentration giving 50% inhibition (IC50 values) of Zn2+, Ni2+, Cd2+ and Hg2+ of initial EROD activity were 107, 16, 1.3 and 0.15 micromolar, respectively. Glutathione (GSH) at 0.5 mM final concentration, completely reversed Ni2+ and Cd2+ inhibition of EROD activity indicating the protective action of GSH.