Indução de danos Oxidativos em celulas de mamifero por isoproterenol e cobre

AUTOR(ES)
DATA DE PUBLICAÇÃO

2001

RESUMO

Isoproterenol (IP) is a synthetic catecholamine of great pharmacological interest, as it is the most potent B-adrenergic known agonist. Recent works revealed the involvement of IP oxidation reactions in cardiotoxicity mechanisms. Copper is an essential microelement which has a fundamental role in living organisms metabolism. In high concentration copper is extremely toxic, as iIIustrated by neurodegenerative dysfunctions such as Menkes and Wilson diseases. Studies on IP oxidation have shown that transition metais, specially CU2+, are effective catalysers of such reaction. This research presents some toxic effects of IP associated to Cu2+ on protein and on DNA in vitra, and on V79 Chinese hamster lung fibroblasts culture. IP/Cu2+ complex inducted carbonils formation in aminoacids and fragmentation of BSA polipeptidic chain, as well as formation of 8-0H-2 -deoxiguanosine in Calf thimus DNA. System containing up to 7,OJJM IP, associated to Cu2+ (2SJJM) totally inhibited cellular proliferation. Oxidation of IP/Cu2+ caused other functional alterations, such as loss of cellular adhesion to culture plates and loss of cellular viability. Conditions containing IP isolated from the metal did not produce significative effects. Morphological alterations were found in cells treated with IP/Cu2+, generating loss of fibroblasts typical morphology, mainly by bubbles appearance and cellular spreading which evidenciated nuclei and nucleolus. Antioxidants CA T and GSH respectively inhibited partially or completely the reaction of IP/Cu2+. GSH prevented lesions in cells morphology inducted by IP/Cu2+. It was also verified that the oxidant system leads to destruction of ali citoskeleton filament analysed (vimentine, actine, a-tubuline and lamin B) and to appearance of drastic nuclear alterations, like increase in DNA index and appearance of picnotic nuclei. Obtained results demonstrated the critical role of copper " on IP toxicity. Observed citotoxic effects suggest a probable interruption of cellular cycle and cellular death from apoptosis on V79 treated cells

ASSUNTO(S)

cobre oxidação citoesqueleto

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