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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Oxidative/Nitrative Mechanism of Molsidomine Mitotoxicity Assayed by the Cytochrome c Reaction with SIN-1 in Models of Biological Membranes

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Author(s):
de Barros, Marcelo Paes [1] ; Araujo-Chaves, Juliana Casares [2] ; Brito, Adrianne Marlise Mendes [2] ; Nantes-Cardoso, Iseli Lourenco [2]
Total Authors: 4
Affiliation:
[1] Cruzeiro do Sul Univ, Inst Phys Act Sci & Sports ICAFE, Interdisciplinary Program Hlth Sci, BR-01506000 Sao Paulo, SP - Brazil
[2] Univ Fed ABC, Ctr Ciencias Nat & Humanas, BR-09210580 Santo Andre, SP - Brazil
Total Affiliations: 2
Document type: Journal article
Source: Chemical Research in Toxicology; v. 33, n. 11, p. 2775-2784, NOV 16 2020.
Web of Science Citations: 0
Abstract

Molsidomine is currently used as a vasodilator drug for the treatment of myocardial ischemic syndrome and congestive heart failure, although still presenting some mitochondrial-targeted side effects in many human cells. As a model of molsidomine mitotoxicity, the reaction of cytochrome c with phosphatidylserine (PS)- and cardiolipin (CL)-containing liposomes was investigated in oxidative/nitrosative conditions imposed by SIN-1 decomposition, which renders peroxynitrite (ONOO-) as a main reactive product. In these conditions, the production of thiobarbituric acid-reactive substance (TBARs) and LOOH was affected by the lipid composition and the oxidative/nitrative conditions used. The oxidative/nitrative conditions were the exposure of lipids to SIN-1 decomposition, native cytochrome c after previous exposure to SIN- 1, concomitantly to SIN-1 and native cytochrome c, native cytochrome c, and cytochrome c modified by SIN-1 that presents a lessrhombic heme iron (L-R cytc). TBARs and LOOH production by lipids and cytochrome c exposed concomitantly to SIN-1 differed from that obtained using L-R cytc and featured similar effects of SIN-1 alone. This result suggests that lipids rather than cytochrome c are the main targets for oxidation and nitration during SIN-1 decomposition. PS- and CL-containing liposomes challenged by SIN-1 were analyzed by Fourier transform infrared spectroscopy that revealed oxidation, trans-isomerization, and nitration. These products are consistent with reaction routes involving lipids and NOx formed via peroxynitrite or direct reaction of NO center dot with molecular oxygen that attacks LOOH and leads to the formation of substances that are not reactive with thiobarbituric acid. (AU)

FAPESP's process: 15/17688-0 - Metallic Nanostructures Associated to Porphyrins, Cytochrome c and Methylene Blue: Fundamental Studies for Applications for Biological Systems and Energy
Grantee:Iseli Lourenço Nantes Cardoso
Support Opportunities: Regular Research Grants
FAPESP's process: 17/06032-2 - Biochemical, physiological and transcriptomic strategies to study the relationship between carotenoids, oxidative stress and Citrus fruit quality
Grantee:Marcelo Paes de Barros
Support Opportunities: Scholarships abroad - Research
FAPESP's process: 17/02317-2 - Interfaces in materials: electronic, magnetic, structural and transport properties
Grantee:Adalberto Fazzio
Support Opportunities: Research Projects - Thematic Grants