title: Thiosemicarbazone derivate protects from AAPH and Cu2+ -induced LDL oxidation.
abstract: OBJECTIVE
  Several lines of evidence support the hypotheses that the oxidation of low density lipoprotein (LDL) may play a crucial role in the initiation and progression of atherosclerosis. Oxidative stress is one of the causes of the overproduction of reactive species that increase the formation of oxidized LDL. Thiosemicarbazones are compounds used in anticancer, antiviral and antifungal therapy; however, its redox activity has been controversial. Thus, we tested, in vitro, a possible antioxidant activity of a thiosemicarbazone derivate, the isatin-3-N(4)-benzilthiosemicarbazone (IBTC).
  
  
  METHODS
  We measured the conjugated diene formation in serum and LDL as well as the loss of tryptophan fluorescence in LDL induced by two oxidant agents, 2,2-azobis(2-amidinopropane dihydrochloride) (AAPH) and Cu(2+). Thiobarbituric acid reactive substances (TBARS) formation in LDL and in different rat tissues was also assessed. The toxicity of IBTC was measured using aortic slices viability assay.
  
  
  RESULTS
  Our results show that IBTC significantly reduced the AAPH and Cu(2+)-induced formation of conjugated dienes, increased in a dose-dependent manner the lag phase and the t(1/2) of tryptophan fluorescence, and reduced the TBARS formation in LDL, plasma and rat tissues, showing no toxicity to aortic slices.
  
  
  CONCLUSIONS
  These results indicate that IBTC is a good antioxidant and a promising antiatherogenic agent for further studies in vivo.
authors.affiliation: Departamento de Química, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Campus UFSM, Santa Maria, RS, Brazil.
authors.forename: Rômulo Pillon
authors.initials: RP
authors.lastname: Barcelos
authors.forename: Rafael de Lima
authors.initials: Rde L
authors.lastname: Portella
authors.forename: Edovando José Flores
authors.initials: EJ
authors.lastname: da Rosa
authors.forename: Alexandra de Souza
authors.initials: Ade S
authors.lastname: Fonseca
authors.forename: Leandro
authors.initials: L
authors.lastname: Bresolin
authors.forename: Vanessa
authors.initials: V
authors.lastname: Carratu
authors.forename: Félix Alexandre Antunes
authors.initials: FA
authors.lastname: Soares
authors.forename: Nilda Vargas
authors.initials: NV
authors.lastname: Barbosa
mesh_terms: D000578:Amidines / Q000633:toxicity*; D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology; D050197:Atherosclerosis / Q000378:metabolism / Q000503:physiopathology*; D003300:Copper / Q000633:toxicity*; D005453:Fluorescence; D007510:Isatin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects; D008077:Lipoproteins, LDL / Q000378:metabolism*; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000502:physiology*; D051381:Rats; D017392:Thiobarbituric Acid Reactive Substances
chemical_list: D000578:Amidines; D000975:Antioxidants; D008077:Lipoproteins, LDL; D017392:Thiobarbituric Acid Reactive Substances; C019440:isatin isothiosemicarbazone; C046728:2,2'-azobis(2-amidinopropane); D003300:Copper; D007510:Isatin