Low-dose endotoxin induces late preconditioning, increases peroxynitrite formation, and activates STAT3 in the rat heart

Márton Pipicz, Gabriella F. Kocsis, László Sárváry-Arantes, Péter Bencsik, Zoltán V. Varga, Péter Ferdinandy, T. Csont

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Administration of low-dose endotoxin (lipopolysaccharide, LPS) 24 h before a lethal ischemia induces pharmacological late preconditioning. The exact mechanism of this phenomenon is not clear. Here we aimed to investigate whether low-dose LPS exerts late effects on peroxynitrite formation and activation of Akt, Erk, and STAT3 in the heart. MaleWistar rats were injected with LPS (S. typhimurium; 0.5 mg/kg i.p.) or saline. Twenty-four hours later, hearts were isolated, perfused for 10 min, and then used for biochemical analyses. LPS pretreatment enhanced cardiac formation of the peroxynitrite marker 3-nitrotyrosine. LPS pretreatment also increased cardiac levels of the peroxynitrite precursor nitric oxide (NO) and superoxide. The activities of Ca2+-independent NO synthase and xanthine oxidoreductase increased in LPS-pretreated hearts. LPS pretreatment resulted in significantly enhanced phosphorylation of STAT3 and non-significantly increased phosphorylation of Akt without affecting the activation of Erk. In separate experiments, isolated working hearts were subjected to 30 min global ischemia and 20 min reperfusion. LPS pretreatment significantly improved ischemia-reperfusion-induced deterioration of cardiac function. We conclude that LPS pretreatment enhances cardiac peroxynitrite formation and activates STAT3 24 h later, which may contribute to LPS-induced late preconditioning.

Original languageEnglish
Article number433
JournalMolecules
Volume22
Issue number3
DOIs
Publication statusPublished - Mar 1 2017

Fingerprint

endotoxins
preconditioning
Peroxynitrous Acid
Endotoxins
pretreatment
rats
Lipopolysaccharides
Rats
ischemia
dosage
phosphorylation
nitric oxide
xanthines
activation
Phosphorylation
Ischemia
inorganic peroxides
deterioration
markers
Reperfusion

Keywords

  • Cardioprotection
  • INOS
  • ONOO
  • Oxidative stress
  • SAFE pathway
  • XOR

ASJC Scopus subject areas

  • Medicine(all)
  • Organic Chemistry

Cite this

Low-dose endotoxin induces late preconditioning, increases peroxynitrite formation, and activates STAT3 in the rat heart. / Pipicz, Márton; Kocsis, Gabriella F.; Sárváry-Arantes, László; Bencsik, Péter; Varga, Zoltán V.; Ferdinandy, Péter; Csont, T.

In: Molecules, Vol. 22, No. 3, 433, 01.03.2017.

Research output: Contribution to journalArticle

Pipicz, Márton ; Kocsis, Gabriella F. ; Sárváry-Arantes, László ; Bencsik, Péter ; Varga, Zoltán V. ; Ferdinandy, Péter ; Csont, T. / Low-dose endotoxin induces late preconditioning, increases peroxynitrite formation, and activates STAT3 in the rat heart. In: Molecules. 2017 ; Vol. 22, No. 3.
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