Medicina - Acute copper toxicity associated with mitochondrial dysfunction, oxidative damage and multiorganic failure.

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Summary *

Cytosolic and mitochondrial oxidative damage (OD) is associatedwith the dose of Cu(II) administered. Previous results shown thatCu(II) doses of less than 5 mg/kg (intraperitoneal (ip) administration),produced cytosolic OD; nevertheless, at slightly higher andtoxic doses (6-6.5 mg/kg), the oxidation of mitochondrial phospholipidsaffects the functionality of mitochondria, and at doses greaterthan 7 mg/kg animals die before the hour after acute treatment. Theaim of this research is to evaluate if acute toxic effects of Cu(II)are associated to mitochondrial dysfunction, OD and multiorganicfailure. Sprague Dawley male rats (200 g) received Cu(II) at doseof 6.5-7.5 mg/kg (ip) and were scarified at 1 h and 6 h after treatment.The livers, brains, hearts, and lungs of the rats were excisedand the samples were processed according to routine methodsfor obtaining histopathological preparations that were stained withhematoxylin-eosin. Phospholipid oxidation was measured as thiobarbituricacid reactive substances (TBARS) and mitochondrialfunction (oxygen uptake, ΔO2) was evaluated using a Clark type oxygenelectrode. Autopsy of these rats indicated that all organs wereaffected, mainly the heart, in which foci of necrosis were observedin the cardiac tissue. TBARS increased in all the organs evaluatedin a dose depended manner (2 to 4 fold at dose 6.5 and 7.5 mg/kg respectively, p<0.01) and mitochondrial ΔO2 decreased with malate-glutamate as substrate mainly in heart and brain (36 and 35%with 6.5 mg/kg dose, and 42 and 27% at dose 7.5 mg/kg, p<0.05,respectively), lung (42%, p<0.05, at the lowest dose) and liver (41%,p<0.001, at the highest dose). With succinate as substrate, the ΔO2decreased 30% (p<0.01, 6.5 mg/kg) and 70% (p<0.001, 7.5 mg/kg)in liver and 30% (p<0.05, 7.5 mg/kg) in brain mitochondria. Theseresults indicate that OD and mitochondrial bioenergetic dysfunctionare processes associated to the histological damage and precedesthe rat death.Keywords: oxidative stress, copper, lipid peroxidation, mitochondria Information provided by the agent in SIGEVA