Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5848085 | Chemico-Biological Interactions | 2013 | 7 Pages |
Abstract
The sydnone SYD-1 (3-[4-chloro-3-nitrophenyl]-1,2,3-oxadiazolium-5-olate] possesses important antitumor activity against Sarcoma 180 and Ehrlich tumors. We previously showed that SYD-1 depresses mitochondrial phosphorylation efficiency, which could be involved in its antitumoral activity. Considering the important role of mitochondria in the generation of reactive oxygen species (ROS) and the involvement of ROS in cell death mechanisms, we evaluated the effects of SYD-1 on oxidative stress parameters in rat liver mitochondria. SYD-1 (0.5 and 0.75 μmol mgâ1 protein) inhibited the lipoperoxidation induced by Fe3+/ADP-oxoglutarate by approximately 75% and promoted total inhibition at the highest concentration tested (1.0 μmol mgâ1 protein). However, SYD-1 did not affect lipoperoxidation started by peroxyl radicals generated by α-αâ²-azodiisobutyramidine dihydrochloride. The mesoionic compound (0.25-1.0 μmol mgâ1 protein) demonstrated an ability to scavenge superoxide radicals, decreasing their levels by 9-19%. The activities of catalase and superoxide dismutase did not change in the presence of SYD-1 (0.25-1.0 μmol mgâ1 protein). SYD-1 inhibited mitochondrial swelling dependent on the formation/opening of the permeability transition pore induced by Ca2+/phosphate by approximately 30% (1.0 μmol mgâ1 protein). When Ca2+/H2O2 were used as inducers, SYD-1 inhibited swelling only by approximately 12% at the same concentration. NADPH oxidation was also inhibited by SYD-1 (1.0 μmol mgâ1 of protein) by approximately 48%. These results show that SYD-1 is able to prevent oxidative stress in isolated mitochondria and suggest that the antitumoral activity of SYD-1 is not mediated by the increasing generation of ROS.
Keywords
TRISFCCPPTPBHTNBTHEPESTBARSAAPHEGTAPMSCAT4-(2-hydroxyethyl)-1-piperazine ethanesulfonic acidBSADMSOMn-SODROSnitroblue tetrazoliumbovine serum albuminPermeability transition poremitochondrial permeability transitionCSAbutylhydroxytolueneMesoionic compoundsTris(hydroxymethyl)-aminomethaneOxidative stressDimethylsulfoxidemanganese superoxide dismutaseSydnonesCyclosporine Aphenazine methosulfatethiobarbituric acid reactive substancesCatalaseReactive oxygen species
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Authors
Gustavo Jabor Gozzi, Amanda do Rocio Andrade Pires, Glaucia Regina Martinez, Maria Eliane Merlin Rocha, Guilhermina Rodrigues Noleto, Aurea Echevarria, André Vinicius Canuto, SÃlvia Maria Suter Correia Cadena,