Rat liver mitochondrial dysfunction by addition of copper(II) or iron(III) ions.
Increased copper (Cu) and iron (Fe) levels in liver and brain are associated to oxidative stress and damage with increased phospholipid oxidation process. The aim of this work was to assess the toxic effects of Cu2+and Fe3+addition to rat liver mitochondria by determining mitochondrial respiration in states 3 (active respiration) and 4 (resting respiration), and phospholipid peroxidation. Both, Cu2+and Fe3+produced decreases in O2consumption in a concentration-dependent manner in active state 3: both ions by 42% with malate-glutamate as complex I substrate (concentration for half maximal response (C50) 60μM Cu2+and 1.25mM Fe3+), and with succinate as complex II substrate: 64-69% with C50of 50μM Cu2+and with C50of 1.25mM of Fe3+. Respiratory control decreased with Cu2+(C5050μM) and Fe3+(C501.25-1-75mM) with both substrates. Cu2+produced a 2-fold increase and Fe3+a 5-fold increase of thiobarbituric acid-reactive substances (TBARS) content from 25μM Cu2+(C5040μM) and from 100μM Fe3+(C501.75mM). Supplementations with Cu2+and Fe3+ions induce mitochondrial dysfunction with phospholipid peroxidation in rat liver mitochondria. Although is proved that a Fenton/Haber Weiss mechanism of oxidative damage occurs in metal-ion induced mitochondrial toxicity, slightly different responses to the metal ions suggest some differences in the mechanism of intracellular toxicity. The decreased rates of mitochondrial respiration and the alteration of mitochondrial function by phospholipid and protein oxidations lead to mitochondrial dysfunction, cellular dyshomeostasis and cell death.
University of Buenos Aires, School of Pharmacy and Biochemistry, Department of General and Inorganic Chemistry, C1113AAD Buenos Aires, Argentina.
Christian
C
Saporito-Magriñá
University of Buenos Aires, School of Pharmacy and Biochemistry, Department of General and Inorganic Chemistry, C1113AAD Buenos Aires, Argentina.
Rosario
R
Musacco-Sebio
University of Buenos Aires, School of Pharmacy and Biochemistry, Department of General and Inorganic Chemistry, C1113AAD Buenos Aires, Argentina.
Juan M
JM
Acosta
University of Buenos Aires, School of Pharmacy and Biochemistry, Department of General and Inorganic Chemistry, C1113AAD Buenos Aires, Argentina.
Sofía
S
Bajicoff
University of Buenos Aires, School of Pharmacy and Biochemistry, Department of General and Inorganic Chemistry, C1113AAD Buenos Aires, Argentina.
Paola
P
Paredes-Fleitas
University of Buenos Aires, School of Pharmacy and Biochemistry, Department of General and Inorganic Chemistry, C1113AAD Buenos Aires, Argentina.
Alberto
A
Boveris
University of Buenos Aires, School of Pharmacy and Biochemistry, Department of General and Inorganic Chemistry, C1113AAD Buenos Aires, Argentina. Electronic address: mrepetto@ffyb.uba.ar.
Marisa G
MG
Repetto
D000818:Animals; D003300:Copper / Q000494:pharmacology*; D042967:Electron Transport Complex I / Q000378:metabolism; D007501:Iron / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D008930:Mitochondria, Liver / Q000378:metabolism* / Q000473:pathology; D024101:Mitochondrial Proteins / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects*; D010743:Phospholipids / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D024101:Mitochondrial Proteins; D010743:Phospholipids; D003300:Copper; D007501:Iron; D042967:Electron Transport Complex I
Copper ions; Iron ions; Liver oxidative stress and damage; Metal toxicity; Mitochondria; Oxygen consumption