Abstract |
Acute liver failure (ALF) remains an extremely poor prognosis and high mortality; with no effective treatments. The endotoxin tolerance (ET) phenotype has been reported to exhibit protective activities in several sepsis models. We now investigated the effects and underlying intraperitoneal injection of the same volume of pyrogen-free 0.9% sodium chloride instead of LPS for five consecutive days before D-GalN/LPS injection in rats. The serum levels of TNF-α, IL-6, ALT, AST and TBiL from ET + ALF group and ALF group were measured at different time points. Our results showed that ET + ALF group markedly reduced the serum levels of TNF-α, IL-6, ALT, AST and TBiL and histological features in the ET + ALF group were improved significantly. Furthermore, LPS pre-treatment inhibited D-GalN/LPS-induced NF-κB activation, Bax activation, signal transducer and activator of transcription-1 (STAT1) and signal transducer and activator of transcription-3 (STAT3) activities. LPS pre-treatment also significantly enhance the expression of suppressors of cytokine signaling 1 (SOCS1) and suppressors of cytokine signaling 3 (SOCS3). Our experimental data indicated that ET might alleviate D-GalN/LPS-induced ALF by inhibiting the inflammatory response, inactivation of STAT1 and STAT3 and up-regulation of SOCS1 and SOCS3.
|
Authors | Jin-Zhong Dong, Li-Ping Wang, Sai-Nan Zhang, Ke-Qing Shi, Shao-Long Chen, Nai-Bin Yang, Shun-Lan Ni, Jian-Hua Zhu, Ming-Qin Lu |
Journal | International journal of clinical and experimental pathology
(Int J Clin Exp Pathol)
Vol. 7
Issue 11
Pg. 7399-408
( 2014)
ISSN: 1936-2625 [Electronic] United States |
PMID | 25550775
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
- Cytokines
- Endotoxins
- Interleukin-6
- Lipopolysaccharides
- NF-kappa B
- Suppressor of Cytokine Signaling Proteins
- Tumor Necrosis Factor-alpha
- Galactosamine
|
Topics |
- Animals
- Cytokines
(blood)
- Disease Models, Animal
- Endotoxins
(pharmacology)
- Galactosamine
(adverse effects)
- Interleukin-6
(blood)
- Lipopolysaccharides
(adverse effects, pharmacology)
- Liver
(drug effects, metabolism)
- Liver Failure, Acute
(prevention & control)
- Male
- NF-kappa B
(blood)
- Rats
- Rats, Sprague-Dawley
- Signal Transduction
(drug effects)
- Specific Pathogen-Free Organisms
- Suppressor of Cytokine Signaling Proteins
(metabolism)
- Tumor Necrosis Factor-alpha
(blood)
- Up-Regulation
|