Heavy metal inhibition of EROD activity in liver microsomes from the bass Dicentrarchus labrax exposed to organic xenobiotics: Role of GSH in the reduction of heavy metal effects

In vitro effects of Cu2+, Hg2+ and of CH3Hg+ on fish liver microsomal EROD activity have been studied. Liver microsomes from the fish Dicentrarchus labrax, treated with β-naphthoflavone (50 mg/kg) or benzo-a-pyrene (20 mg/kg), showed a 4 to 15-fold increase of EROD activity. Addition to the reaction mixture of nmolar concentrations of Cu2+, Hg2+ and CH3Hg+ significantly decreased EROD activity, micromolar concentrations totally inhibited the enzyme, while treatments with mixtures of nanomolar Cu2+, Hg2+ and CH3Hg+ exerted an additive inhibitory effect. Addition of physiological concentrations of GSH drastically reduced the heavy metal inhibitory effects. These results demonstrate that fish liver EROD activity is highly sensitive to extremely low concentrations of heavy metals, also suggesting that GSH plays a fundamental role as a first-line defense against heavy-metal cytotoxicity.