New thiazolidinedione LPSF/GQ-2 inhibits NFκB and MAPK activation in LPS-induced acute lung inflammation.
Int Immunopharmacol
; 57: 91-101, 2018 Apr.
Article
em En
| MEDLINE
| ID: mdl-29475100
ABSTRACT
Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are responsible for high mortality rates in critical patients. Despite >50â¯years of intensive research, there is no pharmacologically effective treatment to treat ALI. PPARs agonists, chemically named thiazolidinediones (TZDs) have emerged as potential drugs for the treatment of ALI and ARDS due to their anti-inflammatory efficacy. The present study aims to evaluate the potential anti-inflammatory effects of new TZDs derivatives, LPSF/GQ-2 and LPSF/RA-4, on ALI induced by LPS. BALB/c mice were divided into five groups 1) Control; 2) LPS intranasal 25⯵g; 3) LPSF/GQ-2 30â¯mg/kgâ¯+â¯LPS; 4) LPSF/RA-4 20â¯mg/kgâ¯+â¯LPS; and 5) DEXA 1â¯mg/Kgâ¯+â¯LPS. BALF analyses revealed that LPSF/GQ-2 and LPSF/RA-4 reduced NO levels in BALF and inflammatory cell infiltration induced by LPS. MPO levels were also reduced by the LPSF/GQ-2 and LPSF/RA-4 pre-treatments. In contrast, histopathological analyses showed better tissue protection with LPSF/GQ-2 than DEXA and LPSF/RA-4 groups. Similarly, LPSF/GQ-2 reduced inflammatory markers (IL-1, iNOS, TNFα, IL-1ß, IL-6) better than LPSF/RA-4. The LPSF/GQ-2 anti-inflammatory action could be attributed to the inhibition of NFκB, ERK, p38, and PARP pathways. In contrast, LPSF/RA-4 had no effect on the expression of p38, JNK, NFκB. The present study indicates that LPSF/GQ-2 presents a potential therapeutic role as an anti-inflammatory drug for ALI.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pneumonia
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Síndrome do Desconforto Respiratório
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NF-kappa B
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Tiazolidinedionas
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Lesão Pulmonar Aguda
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Anti-Inflamatórios
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Int Immunopharmacol
Assunto da revista:
ALERGIA E IMUNOLOGIA
/
FARMACOLOGIA
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Brasil