Oral butyrate reduces oxidative stress in atherosclerotic lesion sites by a mechanism involving NADPH oxidase down-regulation in endothelial cells.
Butyrate is a 4-carbon fatty acid that has antiinflammatory and antioxidative properties. It has been demonstrated that butyrate is able to reduce atherosclerotic development in animal models by reducing inflammatory factors. However, the contribution of its antioxidative effects of butyrate on atherogenesis has not yet been studied. We investigated the influence of butyrate on oxidative status, reactive oxygen species (ROS) release and oxidative enzymes (NADPH oxidase and iNOS) in atherosclerotic lesions of ApoE(-/-) mice and in oxLDL-stimulated peritoneal macrophages and endothelial cells (EA.hy926). The lesion area in aorta was reduced while in the aortic valve, although lesion area was unaltered, superoxide production and protein nitrosylation were reduced in butyrate-supplemented mice. Peritoneal macrophages from the butyrate group presented a lower free radical release after zymosan stimulus. When endothelial cells were pretreated with butyrate before oxLDL stimulus, the CCL-2 and superoxide ion productions and NADPH oxidase subunit p22phox were reduced. In macrophage cultures, in addition to a reduction in ROS release, nitric oxide and iNOS expression were down-regulated. The data suggest that one mechanism related to the effect of butyrate on atherosclerotic development is the reduction of oxidative stress in the lesion site. The reduction of oxidative stress related to NADPH oxidase and iNOS expression levels associated to butyrate supplementation attenuates endothelium dysfunction and macrophage migration and activation in the lesion site.
Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais; Departamento de Fisiologia, Universidade Federal de Minas Gerais.
Edenil C
EC
Aguilar
Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais.
Lana Claudinez Dos
LC
Santos
Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais.
Alda J
AJ
Leonel
Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais.
Jamil Silvano
JS
de Oliveira
Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais.
Elândia Aparecida
EA
Santos
Departamento de Farmacologia, Universidade Federal de Minas Gerais.
Juliana M
JM
Navia-Pelaez
Departamento de Fisiologia, Universidade Federal de Minas Gerais.
Josiane Fernandes
JF
da Silva
Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais.
Bárbara Pinheiro
BP
Mendes
Departamento de Farmacologia, Universidade Federal de Minas Gerais.
Luciano S A
LS
Capettini
Departamento de Nutrição, Universidade Federal de Lavras.
Lilian G
LG
Teixeira
Departamento de Fisiologia, Universidade Federal de Minas Gerais.
Virginia S
VS
Lemos
Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais. Electronic address: jalvarezleite@gmail.com.
Jacqueline I
JI
Alvarez-Leite
D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D050197:Atherosclerosis / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D020148:Butyric Acid / Q000627:therapeutic use*; D002478:Cells, Cultured; D019587:Dietary Supplements; D004730:Endothelium, Vascular / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D004794:Enzyme Repression; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D006801:Humans; D008077:Lipoproteins, LDL / Q000009:adverse effects; D008262:Macrophage Activation; D017737:Macrophages, Peritoneal / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D018345:Mice, Knockout; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000378:metabolism; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism
D000975:Antioxidants; D015415:Biomarkers; D008077:Lipoproteins, LDL; D017382:Reactive Oxygen Species; C099252:oxidized low density lipoprotein; D020148:Butyric Acid; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D019255:NADPH Oxidases
Atherosclerosis; Butyrate; Lipids; Oxidative stress; Reactive oxygen species; Short chain fatty acids