Mitochondrial dysfunction and oxidative damage due to chronic copper toxicity in brain.

MUSACCO SEBIO, ROSARIO; SAPORITO MAGRIÑÁ, CHRISTIAN; SEMPRINE, JIMENA; ARAUJO, JAVIER; REPETTO, MARISA

Buenos Aires

Congreso; VIII International Congress. Society for Free Radical Biology and Medicine.; 2013

Society for Free Radical Biology and Medicine

Brain copper accumulation produces oxidative damage and mitochondrial dysfunction. Male Sprague-Dawley rats (150 g) received Cu(II) in the drinking water (0.5 g/L) for 21 days. Results showed significant increases of in vivo organ chemiluminescence (125%) (increased rate of free-radical mediated reactions), and of lipid (100%) and protein (25%) endogenous oxidation products (controls at day 0, 19 cps/cm2; 5.9 nmol TBARS/g brain; and 134 nmol protein carbonyls/g brain). Significant increases were also observed in tissue and mitochondrial respiration. Brain cortex respiration increased by 85% (control, 507 nmol O2/min.g) since day 7. Mitochondrial O2 consumption with malate-glutamate, increased by 77% and 65% after 21 days in states 4 and 3 (controls at day 0, 4.7 and 17.0 nmol O2/min.mg protein in states 4 and 3. With succinate, the increases were 79% and 33% in both states (controls at day 0, 9.5 and 23.9 nmol O2/min.mg protein in states 4 and 3). Mitochondrial complex I and Mn-SOD activities decreased by 20 and 30% (controls, 130 nmol NADH2/min.mg protein; and 2.6 U/mg protein). Cu toxicity produces mitochondrial dysfunction by inhibition of complex I and by mitochondrial uncoupling. The increased cortex and mitochondrial O2 consumption is explained by mild uncoupling by decreased activity of mtNOS.