Mechanisms underlying iron and copper ions toxicity in biological systems: Pro-oxidant activity and protein-binding effects

• Published in: Chemico-biological interactions 2010-10, Vol.188 (1), p.220-227
• Main Authors: Letelier, María Eugenia, Sánchez-Jofré, Sebastián, Peredo-Silva, Liliana, Cortés-Troncoso, Juan, Aracena-Parks, Paula
• Format: Article
• Language: English
• Subjects: Acetylcysteine; Acetylcysteine - pharmacology; Animals; Catechin; Catechin - pharmacology; Copper; Copper - toxicity; Glutathione Peroxidase - antagonists & inhibitors; Iron; Iron - toxicity; Lipid peroxidation; Lipid Peroxidation - drug effects; Male; N-Acetylcysteine; Oxidants - toxicity; Proteins - metabolism; Rats; Rats, Sprague-Dawley; Thiol proteins
• ISSN: 0009-2797; 1872-7786
• DOI: 10.1016/j.cbi.2010.06.013

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.