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Doctoral Thesis
DOI
https://doi.org/10.11606/T.42.2014.tde-14032015-105454
Document
Author
Full name
Vinicius de Andrade Oliveira
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2014
Supervisor
Committee
Câmara, Niels Olsen Saraiva (President)
Alves Filho, José Carlos Farias
Boim, Mirian Aparecida
Festuccia, William Tadeu Lara
Fujihara, Clarice Kazue
Title in Portuguese
Ácidos graxos de cadeia curta, produtos do metabolismo da microbiota intestinal, protegem da lesão renal aguda.
Keywords in Portuguese
Acetato
Ácido graxo de cadeia curta
Epigenética
Inflamação
Lesão renal aguda
Microbiota
Abstract in Portuguese
Os ácidos graxos de cadeia curta (AGCC) são produzidos pela microbiota intestinal e possuem papéis anti-inflamatórios e ação inibitória sobre histona deacetilases. A lesão renal aguda (LRA) é caracterizada por uma inflamação renal que influencia a função do rim. Este projeto avaliou se o tratamento com os AGCC impactaria nos desfechos inflamatórios da LRA em camundongos. Foi observado que o tratamento com AGCC, protege da LRA. Esta melhora foi associada a uma menor inflamação e menor taxa de apoptose. Além disso, o tratamento com acetato diminuiu a atividade de histona deacetilase. Administrando bactérias produtoras de acetato, também foi possível observar uma proteção da LRA, junto de uma menor inflamação sistêmica. Esta proteção do AGCC na LRA foi também observada em modelo de LRA secundária à sepse In vitro, o tratamento com AGCC modularam tanto células imunes como células renais sob estímulos inflamatórios e de hipóxia. AGCC modulam processos inflamatórios no rim via ações epigenéticas ou não, podendo ser uma promissora ferramenta na proteção da LRA.
Title in English
Short chain fatty acid, a metabolism product from gut microbiota, protect from acute kidney injury.
Keywords in English
Acetate. Microbiota
Acute kidney injury
Epigenetics
Inflammation
Short chain fatty acid
Abstract in English
Short-Chain Fatty Acids (SCFA) are produced by the intestinal microbiota and have anti-inflammatory and histone deacetylases inhibitors properties. Acute kidney injury (AKI) is characterized by renal inflammation that may impair kidney function. This project evaluated whether treatment with SCFA inflammatory impacts the outcomes of AKI in mice. It was observed that treatment with SCFA protected the AKI. This improvement was associated with less inflammation and lower apoptosis rate. In addition, treatment with acetate decreased the activity of histone deacetylase. Giving bacteria producing acetate, was also observed protection from AKI, along with a lower systemic inflammation. This protection of the AGCC in AKI was also observed in sepsis model. In vitro, SCFA treatment modulated both immune cells and renal cells under hypoxia and inflammatory stimuli. SCFA modulate inflammatory processes in the kidney via epigenetic actions or not, may be a promising tool in the protection of the AKI.
 
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Publishing Date
2015-03-14
 
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