title: Mechanisms underlying iron and copper ions toxicity in biological systems: Pro-oxidant activity and protein-binding effects.
abstract: Iron and copper ions, in their unbound form, may lead to the generation of reactive oxygen species via Haber-Weiss and/or Fenton reactions. In addition, it has been shown that copper ions can irreversibly and non-specifically bind to thiol groups in proteins. This non-specific binding property has not been fully addressed for iron ions. Thus, the present study compares both the pro-oxidant and the non-specific binding properties of Fe(3+) and Cu(2+), using rat liver cytosol and microsomes as biological systems. Our data show that, in the absence of proteins, Cu(2+)/ascorbate elicited more oxygen consumption than Fe(3+)/ascorbate under identical conditions. Presence of cytosolic and microsomal protein, however, differentially altered oxygen consumption patterns. In addition, Cu(2+)/ascorbate increased microsomal lipid peroxidation and decreased cytosolic and microsomal content of thiol groups more efficiently than Fe(3+)/ascorbate. Finally, Fe(3+)/ascorbate and Cu(2+)/ascorbate inhibited in different ways cytosolic and microsomal glutathione S-transferase (GST) activities, which are differentially sensitive to oxidants. Moreover, in the absence of ascorbate, only Cu(2+) decreased the content of cytosolic and microsomal thiol groups and inhibited cytosolic and microsomal GST activities. Catechin partially prevented the damage to thiol groups elicited by Fe(3+)/ascorbate and Cu(2+)/ascorbate but not by Cu(2+) alone. N-Acetylcysteine completely prevented the damage elicited by Cu(2+)/ascorbate, Fe(3+)/ascorbate and Cu(2+) alone. N-Acetylcysteine also completely reversed the damage to thiol groups elicited by Fe(3+)/ascorbate, partially reversed that of Cu(2+)/ascorbate but failed to reverse the damage promoted by Cu(2+) alone. Our data are discussed in terms to the potential damage that the accumulation of iron and copper ions can promote in biological systems.
authors.affiliation: Laboratory of Pharmacology and Toxicology, Department of Pharmacological and Toxicological Chemistry, School of Chemical and Pharmaceutical Sciences, Universidad de Chile, Santiago 8380492, Chile. mel@ciq.uchile.cl
authors.forename: María Eugenia
authors.initials: ME
authors.lastname: Letelier
authors.forename: Sebastián
authors.initials: S
authors.lastname: Sánchez-Jofré
authors.forename: Liliana
authors.initials: L
authors.lastname: Peredo-Silva
authors.forename: Juan
authors.initials: J
authors.lastname: Cortés-Troncoso
authors.forename: Paula
authors.initials: P
authors.lastname: Aracena-Parks
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D002392:Catechin / Q000494:pharmacology; D003300:Copper / Q000633:toxicity*; D005979:Glutathione Peroxidase / Q000037:antagonists & inhibitors; D007501:Iron / Q000633:toxicity*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D016877:Oxidants / Q000633:toxicity*; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D016877:Oxidants; D011506:Proteins; D003300:Copper; D002392:Catechin; D007501:Iron; D005979:Glutathione Peroxidase; D000111:Acetylcysteine