The new vitamin E derivative, ETS-GS, protects against cecal ligation and puncture-induced systemic inflammation in rats.
Inflammation
; 35(2): 545-53, 2012 Apr.
Article
en En
| MEDLINE
| ID: mdl-21603971
ABSTRACT
Sepsis-related systemic inflammation frequently occurs in the critical care setting. Systemic inflammation is implicated in the progression of organ injury, which is associated with a high mortality rate. Recently, vitamin E and glutamic acid have been reported to attenuate inflammation. We therefore investigated whether the vitamin E derivative, ETS-GS, could inhibit the secretion of cytokines and high-mobility group box 1 (HMGB1), and thereby reduce organ damage in a rat model of cecal ligation and puncture (CLP)-induced sepsis. Male Wistar rats weighing 250-300 g were used. Rats received water or ETS-GS (10 mg/kg) by oral administration for 3 weeks, and then sepsis was induced by CLP under sevoflurane anesthesia. Serum levels of interleukin-6, tumor necrosis factor-α, and HMGB1 were determined at 3, 6, and 12 h after CLP; lung histology was assessed at 12 h. Histology results showed markedly reduced interstitial edema and leukocytic infiltration in lung tissue harvested at 12 h in ETS-GS-treated mice compared with untreated controls. ETS-GS treatment also attenuated the CLP-induced increase in serum levels of cytokines and HMGB1. To investigate the mechanisms by which ETS-GS exerts its anti-inflammatory effects, the phosphorylation of Akt, IκBα, and mitogen-activated protein kinase (MAPK) was assessed in mouse macrophage RAW264.7 cells stimulated with LPS, with and without ETS-GS. In these in vitro studies, ETS-GS-induced phosphoinositide 3-kinase (PI3K)-Akt phosphorylation and inhibited IκBα and MAPK phosphorylation. ETS-GS blocked the CLP-induced septic shock response and protected against acute lung injury. This mechanism appeared to be mediated by the induction of PI3K-Akt and the inhibition of IκBα and MAPK phosphorylation. Given these results, ETS-GS shows promise as a potential therapeutic agent for sepsis.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Oligopéptidos
/
Síndrome de Respuesta Inflamatoria Sistémica
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Inflammation
Año:
2012
Tipo del documento:
Article
País de afiliación:
Japón