Simvastatin protects against intestinal ischemia/reperfusion-induced pulmonary artery dysfunction

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Arquivos
art_PERES_Simvastatin_protects_against_intestinal_ischemiareperfusioninduced_pulmonary_artery_dysfunction_2022.PDF (1.66 MB)
Citações na Scopus
3
Tipo de produção
article
Data de publicação
2022
DOI
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Editora
PERGAMON-ELSEVIER SCIENCE LTD
Autores
PERES, Emilia C.
VICTORIO, Jamaira A.
NUNES-SOUZA, Valeria
RABELO, Luiza A.
TAVARES-DE-LIMA, Wothan
DAVEL, Ana Paula
ROSSONI, Luciana V.
Citação
LIFE SCIENCES, v.306, article ID 120851, 10p, 2022
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
Aims: The lung is an important target organ damage in intestinal ischemia/reperfusion (II/R), but mechanisms involved in II/R-induced pulmonary artery (PA) dysfunction, as well as its treatment, are not clear. The present study aimed to investigate the mechanisms involved in the II/R-induced PA dysfunction and a possible protective role of acute simvastatin pretreatment.Main methods: Male Wistar rats were subjected to occlusion of the superior mesenteric artery for 45 min followed by 2 h reperfusion (II/R) or sham-operated surgery (sham). In some rats, simvastatin (20 mg/kg, oral gavage) was administrated 1 h before II/R. Key findings: II/R reduced acetylcholine-induced relaxation and phenylephrine-induced contraction of PA seg-ments, which were prevented by acute simvastatin pretreatment in vivo or restored by inducible nitric oxide synthase (iNOS) inhibition in situ with 1400 W. Elevated reactive oxygen species (ROS) levels and higher nuclear translocation of nuclear factor kappa B (NF Kappa B) subunit p65 were observed in PA of II/R rats and prevented by simvastatin. Moreover, simvastatin increased superoxide dismutase (SOD) activity and endothelial nitric oxide synthase (eNOS) expression in PA of the II/R group as well as prevented the increased levels of interleukin (IL)-1 beta and IL-6 in lung explants following II/R.Significance: The study suggests that pretreatment with a single dose of simvastatin prevents the II/R-induced increase of inflammatory factors and oxidative stress, as well as PA endothelial dysfunction and adrenergic hyporreactivity. Therefore, acute simvastatin administration could be therapeutic for pulmonary vascular disease in patients suffering from intestinal ischemic events.
Palavras-chave
Intestinal ischemia, reperfusion, Pulmonary artery, Simvastatin, iNOS, Oxidative stress, Inflammation
URI
https://observatorio.fm.usp.br/handle/OPI/50720
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Coleções
Artigos e Materiais de Revistas Científicas - FM/Outros
Artigos e Materiais de Revistas Científicas - LIM/11
Artigos e Materiais de Revistas Científicas - ODS/03