title: The antioxidant effect of the mesoionic compound SYD-1 in mitochondria.
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 0.75μmolmg(-1) protein) inhibited the lipoperoxidation induced by Fe(3+)/ADP-oxoglutarate by approximately 75% and promoted total inhibition at the highest concentration tested (1.0μmolmg(-1) protein). However, SYD-1 did not affect lipoperoxidation started by peroxyl radicals generated by α-α'-azodiisobutyramidine dihydrochloride. The mesoionic compound (0.25-1.0μmolmg(-1) 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 (0.25-1.0μmolmg(-1) protein). SYD-1 inhibited mitochondrial swelling dependent on the formation/opening of the permeability transition pore induced by Ca(2+)/phosphate by approximately 30% (1.0μmolmg(-1) protein). When Ca(2+)/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 (1.0μmolmg(-1) 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.
authors.affiliation: Departamento de Bioquímica e Biologia Molecular, Universidade Federal do Paraná, Curitiba, Paraná, Brazil.
authors.forename: Gustavo Jabor
authors.initials: GJ
authors.lastname: Gozzi
authors.forename: Amanda do Rocio Andrade
authors.initials: Ado R
authors.lastname: Pires
authors.forename: Glaucia Regina
authors.initials: GR
authors.lastname: Martinez
authors.forename: Maria Eliane Merlin
authors.initials: ME
authors.lastname: Rocha
authors.forename: Guilhermina Rodrigues
authors.initials: GR
authors.lastname: Noleto
authors.forename: Aurea
authors.initials: A
authors.lastname: Echevarria
authors.forename: André Vinicius
authors.initials: AV
authors.lastname: Canuto
authors.forename: Sílvia Maria Suter Correia
authors.initials: SM
authors.lastname: Cadena
mesh_terms: D000818:Animals; D002374:Catalase / Q000378:metabolism; D005470:Fluorometry; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D010069:Oxadiazoles / Q000378:metabolism / Q000494:pharmacology*; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: C524256:3-(4-chloro-3-nitrolphenyl)-1,2,3-oxadiazolium-5-olate; D010069:Oxadiazoles; D017392:Thiobarbituric Acid Reactive Substances; D013481:Superoxides; D002374:Catalase; D013482:Superoxide Dismutase
keywords: (4-phenyl-5-(4-nitrocinnamoyl)-1,3,4-thiadiazolium-2-phenylamine chloride); 3-[4-chloro-3-nitrophenyl]-1,2,3-oxadiazolium-5-olate]; 4-(2-hydroxyethyl)-1-piperazine ethanesulfonic acid; 4-phenyl-5-(2,4-chlorocinnamoyl)-1,3,4–thiadiazolium-2-phenylamine chlorides; 4-phenyl-5-(4-chlorocinnamoyl)-1,3,4–thiadiazolium-2-phenylamine chlorides; 4-phenyl-5-(4-hydroxycinnamoyl)-1,3,4–thiadiazolium-2-phenylamine chlorides; AAPH; BHT; BSA; CAT; CsA; DMSO; EGTA; FCCP; HEPES; MI-2,4diF; MI-4F; MI-D; MI-J; Mesoionic compounds; Mitochondrial permeability transition; Mn-SOD; NBT; Oxidative stress; PMS; PTP; ROS; SYD-1; Sydnones; TBARS; TRIS; bovine serum albumin; butylhydroxytoluene; catalase; cyclosporine A; dimethylsulfoxide; ethylene glycol-bis(β-aminoethyl-ether)-N,N,N′,N′-tetraacetic acid; manganese superoxide dismutase; nitroblue tetrazolium; p-trifluoro-methoxycarbonylcyanide phenylhydrazone; permeability transition pore; phenazine methosulfate; reactive oxygen species; thiobarbituric acid reactive substances; tris(hydroxymethyl)-aminomethane; α-α′-azodiisobutyramidine dihydrochloride