2,4,6-Trihydroxy-3-geranyl acetophenone suppresses vascular leakage and leukocyte infiltration in lipopolysaccharide-induced endotoxemic mice.
Pharm Biol
; 59(1): 732-740, 2021 Dec.
Article
em En
| MEDLINE
| ID: mdl-34155953
ABSTRACT
CONTEXT Lipopolysaccharide (LPS) exacerbates systemic inflammatory responses and causes excessive fluid leakage. 2,4,6-Trihydroxy-3-geranyl acetophenone (tHGA) has been revealed to protect against LPS-induced vascular inflammation and endothelial hyperpermeability in vitro. OBJECTIVE:
This study assesses the in vivo protective effects of tHGA against LPS-induced systemic inflammation and vascular permeability in endotoxemic mice. MATERIALS ANDMETHODS:
BALB/c mice were intraperitoneally pre-treated with tHGA for 1 h, followed by 6 h of LPS induction. Evans blue permeability assay and leukocyte transmigration assay were performed in mice (n = 6) pre-treated with 2, 20 and 100 mg/kg tHGA. The effects of tHGA (20, 40 and 80 mg/kg) on LPS-induced serum TNF-α secretion, lung dysfunction and lethality were assessed using ELISA (n = 6), histopathological analysis (n = 6) and survivability assay (n = 10), respectively. Saline and dexamethasone were used as the negative control and drug control, respectively.RESULTS:
tHGA significantly inhibited vascular permeability at 2, 20 and 100 mg/kg with percentage of inhibition of 48%, 85% and 86%, respectively, in comparison to the LPS control group (IC50=3.964 mg/kg). Leukocyte infiltration was suppressed at 20 and 100 mg/kg doses with percentage of inhibition of 73% and 81%, respectively (IC50=17.56 mg/kg). However, all tHGA doses (20, 40 and 80 mg/kg) failed to prevent endotoxemic mice from lethality because tHGA could not suppress TNF-α overproduction and organ dysfunction. DISCUSSION ANDCONCLUSIONS:
tHGA may be developed as a potential therapeutic agent for diseases related to uncontrolled vascular leakage by combining with other anti-inflammatory agents.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Acetofenonas
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Floroglucinol
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Permeabilidade Capilar
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Lipopolissacarídeos
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Endotoxemia
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Leucócitos
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Pulmão
Limite:
Animals
Idioma:
En
Revista:
Pharm Biol
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Malásia