title: Apoptotic markers and DNA damage are related to late phase of stroke: Involvement of dyslipidemia and inflammation.
abstract: Oxidative stress and brain inflammation are thought to contribute to the pathophysiology of cerebral injury in acute stroke, leading to apoptosis and cell death. Lipid accumulation may lead to progression of carotid plaques and inflammation, contributing to increased acute stroke risk. However, little is known about these events and markers in the late stroke (>6 months) and if dyslipidemia could contribute to disease's pathophysiology in a later phase. In this case-control study, we recruited patients in the late stroke phase (n=40) and health subjects (control group; n = 40). Dichlorodihydrofluorescein (DCFH), nitrite/nitrate (NOx), Tumor necrosis factor-alpha (TNF-α), Acetylcholinesterase (AChE), Caspase 8 (CASP 8), Caspase 3 (CASP 3) and Picogreen (PG) were measured in periphery blood samples. Furthermore, a correlation among all measured markers (DCFH, NOx, TNF-α, AChE, CASP 8, CASP 3 and PG) was realized. The marker levels were also compared to triglycerides (TG), total (CHO), LDL and HDL cholesterol levels and medications used. Statistical analyses showed that stroke patients presented an increase of DCFH, NOx, TNF-α and AChE levels when compared to control subjects. In addition, we observed that stroke patients had significantly higher CASP 8, CASP 3 and PG levels than control group. A significant correlation between TNF-α with CASP 8 (r = 0.4) and CASP 3 (r = 0.4) levels was observed, but not with oxidative/nitrosative markers. Moreover, we observed that stroke patients with dyslipidemia had significantly higher TNF-α, CASP 8 and CASP 3 levels than stroke without dyslipidemia and control groups. Our findings suggest that oxidative and inflammatory markers may be still increased and lead to caspase activation and DNA damage even after 6 months to cerebral injury. Furthermore, it is plausible to propose that dyslipidemia may contribute to worsen proinflammatory state in a later phase of stroke and an increased risk to new neurovascular events.
authors.affiliation: Centro de Ciências da Saúde, Departamento de Neuropsiquiatria, Universidade Federal de Santa Maria, RS, Brazil; Centro de Ciências da Saúde, Programa de Pós-Graduação em Farmacologia, Universidade Federal de Santa Maria, RS, Brazil.
authors.forename: Eduardo Tanuri
authors.initials: ET
authors.lastname: Pascotini
authors.affiliation: Centro de Ciências da Saúde, Departamento de Neuropsiquiatria, Universidade Federal de Santa Maria, RS, Brazil; Centro de Ciências da Saúde, Programa de Pós-Graduação em Farmacologia, Universidade Federal de Santa Maria, RS, Brazil.
authors.forename: Ariane Ethur
authors.initials: AE
authors.lastname: Flores
authors.affiliation: Centro de Ciências da Saúde, Departamento de Neuropsiquiatria, Universidade Federal de Santa Maria, RS, Brazil; Centro de Ciências Naturais e Exatas, Programa de Pós-graduação em Ciências Biológicas, Bioquímica Toxicológica, Universidade Federal de Santa Maria, RS, Brazil.
authors.forename: Aline
authors.initials: A
authors.lastname: Kegler
authors.affiliation: Centro de Ciências da Saúde, Programa de Pós-Graduação em Farmacologia, Universidade Federal de Santa Maria, RS, Brazil.
authors.forename: Patricia
authors.initials: P
authors.lastname: Gabbi
authors.affiliation: Centro de Ciências da Saúde, Programa de Pós-Graduação em Farmacologia, Universidade Federal de Santa Maria, RS, Brazil.
authors.forename: Guilherme Vargas
authors.initials: GV
authors.lastname: Bochi
authors.affiliation: Centro de Ciências da Saúde, Programa de Pós-Graduação em Farmacologia, Universidade Federal de Santa Maria, RS, Brazil.
authors.forename: Thais Doeler
authors.initials: TD
authors.lastname: Algarve
authors.affiliation: Serviço de Fisioterapia, Hospital Universitário de Santa Maria, RS, Brazil.
authors.forename: Ana Lucia Cervi
authors.initials: AL
authors.lastname: Prado
authors.affiliation: Centro de Ciências da Saúde, Programa de Pós-Graduação em Farmacologia, Universidade Federal de Santa Maria, RS, Brazil.
authors.forename: Marta M M F
authors.initials: MM
authors.lastname: Duarte
authors.affiliation: Centro de Ciências da Saúde, Programa de Pós-Graduação em Farmacologia, Universidade Federal de Santa Maria, RS, Brazil.
authors.forename: Ivana B M
authors.initials: IB
authors.lastname: da Cruz
authors.affiliation: Centro de Ciências da Saúde, Programa de Pós-Graduação em Farmacologia, Universidade Federal de Santa Maria, RS, Brazil.
authors.forename: Rafael Noal
authors.initials: RN
authors.lastname: Moresco
authors.affiliation: Centro de Ciências Naturais e Exatas, Programa de Pós-graduação em Ciências Biológicas, Bioquímica Toxicológica, Universidade Federal de Santa Maria, RS, Brazil; Centro de Educação Física e Desportos, Laboratório de Bioquímica do Exercício (BIOEX), Universidade Federal de Santa Maria, RS, Brazil; Centro de Ciências da Saúde, Programa de Pós-Graduação em Farmacologia, Universidade Federal de Santa Maria, RS, Brazil.
authors.forename: Luiz Fernando Freire
authors.initials: LF
authors.lastname: Royes
authors.affiliation: Centro de Ciências da Saúde, Departamento de Neuropsiquiatria, Universidade Federal de Santa Maria, RS, Brazil; Centro de Ciências Naturais e Exatas, Programa de Pós-graduação em Ciências Biológicas, Bioquímica Toxicológica, Universidade Federal de Santa Maria, RS, Brazil; Centro de Educação Física e Desportos, Laboratório de Bioquímica do Exercício (BIOEX), Universidade Federal de Santa Maria, RS, Brazil; Centro de Ciências da Saúde, Programa de Pós-Graduação em Farmacologia, Universidade Federal de Santa Maria, RS, Brazil. Electronic address: mrfighera@yahoo.com.br.
authors.forename: Michele Rechia
authors.initials: MR
authors.lastname: Fighera
mesh_terms: D000368:Aged; D017209:Apoptosis / Q000502:physiology*; D016022:Case-Control Studies; D020169:Caspases / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D004249:DNA Damage / Q000502:physiology*; D050171:Dyslipidemias / Q000209:etiology*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D009573:Nitrites / Q000378:metabolism; D009930:Organic Chemicals / Q000378:metabolism; D020521:Stroke / Q000150:complications* / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D009573:Nitrites; D009930:Organic Chemicals; C099476:PicoGreen; D014409:Tumor Necrosis Factor-alpha; D002784:Cholesterol; D020169:Caspases
keywords: Caspases; DNA damage; Dyslipidemia; Inflammation; Oxidative stress; Stroke