Glutathione protects heavy metal-induced inhibition of hepatic microsomal ethoxyresorufin O-deethylase activity in Dicentrarchus labrax L

Ecotoxicol Environ Saf. 2004 Jul;58(3):379-85. doi: 10.1016/j.ecoenv.2004.03.003.

Abstract

The in vitro effects of chromium (Cr(VI)), copper (Cu2+), iron (Fe2+), mercury (Hg2+), and zinc (Zn2+) were assessed on liver microsomal ethoxyresorufin O-deethylase (EROD) activity from a sea bass (Dicentrarchus labrax L.) preexposed under laboratory conditions to 2.7 microM beta-naphthoflavone. The reduced glutathione (GSH) protection potential against heavy metal effects was also studied. The heavy metal concentration ranges used for this study were as follows: 10 pM-5 mM Cr(VI), 10 pM-100 microM Cu2+, 10 pM-1 mM Fe2+, 10 pM-10 microM Hg2+, and 10 pM-100 microM Zn2+. Liver microsomal EROD activity was significantly inhibited after in vitro exposure to Cr(VI) (500 microM), Cu2+ (1 microM), Fe2+ (100 microM), Hg2+ (100 pM), and Zn2+ (10 microM). Heavy metals inhibitory effect on liver EROD activity was ordered as follows: Hg2+ > Cu2+ > Zn2+ > Fe2+ > Cr(VI). Protective effects against Hg2+ (1 and 10 microM), Cu2+ (1, 10, and 100 microM), and Zn2+ (10, 50, and 100 microM) were observed in the presence of 0.5 mM GSH by a decrease in liver microsomal EROD activity inhibition. However, 0.5 mM GSH did not protect liver microsomal EROD activity from Cr(VI), and Fe2+-induced inhibition. The effect of metal mixtures (Cu(2+) + Zn(2+), Zn(2+) + Fe(2+), Zn(2+) + Cr(VI), and Cr(VI) + Fe(2+)) (100 microM) on liver microsomal EROD activity was also assessed, revealing a synergistic interaction.

MeSH terms

  • Animals
  • Bass / metabolism*
  • Cytochrome P-450 CYP1A1 / antagonists & inhibitors*
  • Cytochrome P-450 CYP1A1 / biosynthesis
  • Drug Synergism
  • Glutathione / pharmacology*
  • In Vitro Techniques
  • Metals, Heavy / toxicity*
  • Microsomes, Liver / drug effects*
  • Microsomes, Liver / enzymology
  • Portugal
  • Protective Agents / pharmacology*
  • Water Pollutants, Chemical / toxicity*
  • beta-Naphthoflavone

Substances

  • Metals, Heavy
  • Protective Agents
  • Water Pollutants, Chemical
  • beta-Naphthoflavone
  • Cytochrome P-450 CYP1A1
  • Glutathione