Rat liver antioxidant response to iron and copper overloads.
The rat liver antioxidant response to Fe and Cu overloads (0-60mg/kg) was studied. Dose- and time-responses were determined and summarized by t1/2 and C50, the time and the liver metal content for half maximal oxidative responses. Liver GSH (reduced glutathione) and GSSG (glutathione disulfide) were determined. The GSH content and the GSH/GSSG ratio markedly decreased after Fe (58-66%) and Cu (79-81%) loads, with t1/2 of 4.0 and 2.0h. The C50 were in a similar range for all the indicators (110-124μgFe/g and 40-50μgCu/g) and suggest a unique free-radical mediated process. Hydrophilic antioxidants markedly decreased after Fe and Cu (60-75%; t1/2: 4.5 and 4.0h). Lipophilic antioxidants were also decreased (30-92%; t1/2: 7.0 and 5.5h) after Fe and Cu. Superoxide dismutase (SOD) activities (Cu,Zn-SOD and Mn-SOD) and protein expression were adaptively increased after metal overloads (Cu,Zn-SOD: t1/2: 8-8.5h and Mn-SOD: t1/2: 8.5-8.0h). Catalase activity was increased after Fe (65%; t1/2: 8.5h) and decreased after Cu (26%; t1/2: 8.0h), whereas catalase expression was increased after Fe and decreased after Cu overloads. Glutathione peroxidase activity decreased after metal loads by 22-39% with a t1/2 of 4.5h and with unchanged protein expression. GSH is the main and fastest responder antioxidant in Fe and Cu overloads. The results indicate that thiol (SH) content and antioxidant enzyme activities are central to the antioxidant defense in the oxidative stress and damage after Fe and Cu overloads.
Department of General and Inorganic Chemistry, School of Pharmacy and Biochemistry, University of Buenos Aires, C1113AAD Buenos Aires, Argentina.
Rosario
R
Musacco-Sebio
Department of General and Inorganic Chemistry, School of Pharmacy and Biochemistry, University of Buenos Aires, C1113AAD Buenos Aires, Argentina.
Christian
C
Saporito-Magriñá
Department of General and Inorganic Chemistry, School of Pharmacy and Biochemistry, University of Buenos Aires, C1113AAD Buenos Aires, Argentina.
Jimena
J
Semprine
Department of Physics, School of Pharmacy and Biochemistry, University of Buenos Aires, C1113AAD Buenos Aires, Argentina.
Horacio
H
Torti
Department of General and Inorganic Chemistry, School of Pharmacy and Biochemistry, University of Buenos Aires, C1113AAD Buenos Aires, Argentina; Laboratory of Clinical Immunology, Department of Clinical Biochemistry, School of Pharmacy and Biochemistry, University of Buenos Aires, C1113AAD Buenos Aires, Argentina.
Nidia
N
Ferrarotti
Department of Molecular Biology, School of Pharmacy and Biochemistry, University of Buenos Aires, C1113AAD Buenos Aires, Argentina.
Mauricio
M
Castro-Parodi
Department of Molecular Biology, School of Pharmacy and Biochemistry, University of Buenos Aires, C1113AAD Buenos Aires, Argentina.
Alicia
A
Damiano
Department of General and Inorganic Chemistry, School of Pharmacy and Biochemistry, University of Buenos Aires, C1113AAD Buenos Aires, Argentina.
Alberto
A
Boveris
Department of General and Inorganic Chemistry, School of Pharmacy and Biochemistry, University of Buenos Aires, C1113AAD Buenos Aires, Argentina. Electronic address: mrepetto@ffyb.uba.ar.
Marisa G
MG
Repetto
D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000378:metabolism; D002374:Catalase / Q000096:biosynthesis; D003300:Copper / Q000008:administration & dosage*; D005786:Gene Expression Regulation / Q000187:drug effects; D005978:Glutathione / Q000096:biosynthesis; D005979:Glutathione Peroxidase / Q000096:biosynthesis; D007501:Iron / Q000008:administration & dosage*; D015227:Lipid Peroxidation; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D018384:Oxidative Stress; D051381:Rats; D013482:Superoxide Dismutase / Q000096:biosynthesis; D000099156:Superoxide Dismutase 2
D000975:Antioxidants; D002374:Catalase; D003300:Copper; D005978:Glutathione; D005979:Glutathione Peroxidase; D007501:Iron; D013482:Superoxide Dismutase; D000099156:Superoxide Dismutase 2
Antioxidants; Copper; Glutathione; Iron; Liver chemiluminescence; Oxidative damage