17-DMAG, an HSP90 Inhibitor, Ameliorates Multiple Organ Dysfunction Syndrome via Induction of HSP70 in Endotoxemic Rats.
In: PLoS ONE, Jg. 11 (2016-05-25), Heft 5, S. 1-18
Online
academicJournal
Zugriff:
Sepsis is a systemic inflammatory disorder, accompanied with elevated oxidative stress, leading to multiple organ dysfunction syndrome (MODS), and disseminated intravascular coagulation. 17-Dimethylaminoethylamino- 17-demethoxygeldanamycin (17-DMAG), a heat shock protein (HSP) 90 inhibitor, has been reported to possess anti-inflammatory effects. In this study, the beneficial effects of 17-DMAG on lipopolysaccharide (LPS) induced MODS and DIC was evaluated in anesthetized rats. 17-DMAG (5 mg/kg, i.p.) was significantly increased survival rate, and prevented hypotension in LPS (30 mg/kg i.v. infused for 4 h) induced endotoxemia. The elevated levels of alanine aminotransferase (ALT), creatine phosphokinase (CPK), lactate dehydrogenase, creatinine, nitric oxide (NO) metabolites, IL-6, and TNF-α in LPS-exposed rat plasma were significantly reduced by 17-DMAG. Moreover, 17-DMAG suppressed LPS-induced superoxide anion production and caspase 3 activation in heart tissues. LPS induced the prolongation of prothrombin time, and a pronounced decrease in platelet count, which were improved by 17-DMAG. 17-DMAG markedly induced HSP70 and heme oxygenase (HO)-1, and suppressed inducible nitric oxide synthase (iNOS) and phosphorylated NF-κB p65 protein expression in organs 6 h after LPS initiation. Pretreatment with high dose of quercetin (300 mg/kg, i.p.), as an HSP70 inhibitor, reversed the beneficial effects of 17-DMAG on survival rate, plasma levels of ALT, CPK, creatinine, IL-6, and NO metabolites, iNOS induction, and caspase-3 activation in LPS-treated rats. In conclusion, 17-DMAG possesses the anti-inflammatory and antioxidant effects that were proved through LPS-induced acute inflammation, which is associated with induction of HSP70 and HO-1, leading to prevent MODS in sepsis. [ABSTRACT FROM AUTHOR]
Copyright of PLoS ONE is the property of Public Library of Science and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Titel: |
17-DMAG, an HSP90 Inhibitor, Ameliorates Multiple Organ Dysfunction Syndrome via Induction of HSP70 in Endotoxemic Rats.
|
---|---|
Autor/in / Beteiligte Person: | Wang, Yi-Li ; Shen, Hsin-Hsueh ; Cheng, Pao-Yun ; Chu, Yen-Ju ; Hwang, Hwong-Ru ; Lam, Kwok-Keung ; Lee, Yen-Mei |
Link: | |
Zeitschrift: | PLoS ONE, Jg. 11 (2016-05-25), Heft 5, S. 1-18 |
Veröffentlichung: | 2016 |
Medientyp: | academicJournal |
ISSN: | 1932-6203 (print) |
DOI: | 10.1371/journal.pone.0155583 |
Schlagwort: |
|
Sonstiges: |
|