Premium
Pharmacological Preconditioning With Tyrosol, A White Wine Component, Depends On The Activation Of PI‐3 Kinase Pathway In Ischemic Reperfused Rat Myocardium
Author(s) -
Thirunavukkarasu Mahesh,
Samuel Samson Mathews,
Penumathsa SureshVarma,
Zhan Lijun,
Bertelli A.A.E.,
Maulik Nilanjana
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.705.1
Subject(s) - cardioprotection , tyrosol , ischemia , chemistry , pharmacology , ly294002 , reperfusion injury , ischemic preconditioning , apoptosis , pi , medicine , protein kinase b , antioxidant , biochemistry
Tyrosol (2‐(4‐hydroxyphenyl) ethanol) (Tsl) a mono‐phenolic compound, in white wine possesses antioxidant activity & is able to reduce the release of pro‐inflammatory cytokines. The present study sought to determine the mechanism of Tsl mediated cardioprotection from ischemia reperfusion injury. Isolated perfused rat hearts were divided into five groups: ‐ (1) control heart (2.5h of perfusion) (C) (2) hearts subjected to 30min ischemia [I] & 2h reperfusion [R] (IR) (3) perfused with Tsl (1 μM, 20 min) followed by 30 min I & 2h R (TIR) (4) LY294002 (5μM) + Tsl followed by IR (LYTIR) (5) SN50 (18μM) + Tsl followed by IR (SNTIR). We have observed improved post‐ischemic ventricular functional recovery during the 2 hrs of R & the reduced infarct size & cardiomyocyte apoptosis in TIR compared to IR. Increased phosphorylation of pro‐survival proteins Akt & eNOS was observed in TIR treated compared to the IR. The gel‐shift analysis showed significant upregulation of DNA binding activity of NF‐κB in the Tsl treated TIR group compared to non‐treated IR. The use of PI‐3kinase inhibitor, LY294002 & NF‐κB inhibitor SN50 completely blocked Tsl mediated cardioprotection. We therefore demonstrate for the first time that Tsl mediated cardioprotection is by activation of the survival pathway through PI‐3kinase/NF‐κB & maybe used as a novel therapeutic agent against ischemia‐reperfusion injury.