Journal
LIFE SCIENCES
Volume 89, Issue 1-2, Pages 20-28Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.lfs.2011.04.026
Keywords
LDL oxidation; Thiosemicarbazone; Atherosclerosis; Antioxidant compounds; Serum oxidation
Funding
- FINEP, Rede Instituto Brasileiro de Neurociencia (IBN-Net) [01.06.0842-00]
- INCT-National Institute of Science and Technology for Excitotoxicity and Neuroprotection/CNPq
- CNPq
- CAPES
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Aims: 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). Main 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 Cu2+. 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. Key findings: Our results show that IBTC significantly reduced the AAPH and Cu2+-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. Significance: These results indicate that IBTC is a good antioxidant and a promising antiatherogenic agent for further studies in vivo. (C) 2011 Elsevier Inc. All rights reserved.
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