Τίτλος:
Acute administration of the olive constituent, oleuropein, combined with ischemic postconditioning increases myocardial protection by modulating oxidative defense
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Oleuropein, one of the main polyphenolic constituents of olive, is cardioprotective against ischemia reperfusion injury (IRI). We aimed to assess the cardioprotection afforded by acute administration of oleuropein and to evaluate the underlying mechanism. Importantly, since antioxidant therapies have yielded inconclusive results in attenuating IRI-induced damage on top of conditioning strategies, we investigated whether oleuropein could enhance or imbed the cardioprotective manifestation of ischemic postconditioning (PostC). Oleuropein, given during ischemia as a single intravenous bolus dose reduced the infarct size compared to the control group both in rabbits and mice subjected to myocardial IRI. None of the inhibitors of the cardioprotective pathways, L-NAME, wortmannin and AG490, influence its infarct size limiting effects. Combined oleuropein and PostC cause further limitation of infarct size in comparison with PostC alone in both animal models. Oleuropein did not inhibit the calcium induced mitochondrial permeability transition pore opening in isolated mitochondria and did not increase cGMP production. To provide further insights to the different cardioprotective mechanism of oleuropein, we sought to characterize its anti-inflammatory potential in vivo. Oleuropein, PostC and their combination reduce inflammatory monocytes infiltration into the heart and the circulating monocyte cell population. Oleuropein's mechanism of action involves a direct protective effect on cardiomyocytes since it significantly increased their viability following simulated IRI as compared to non-treated cells. Οleuropein confers additive cardioprotection on top of PostC, via increasing the expression of the transcription factor Nrf-2 and its downstream targets in vivo. In conclusion, acute oleuropein administration during ischemia in combination with PostC provides robust and synergistic cardioprotection in experimental models of IRI by inducing antioxidant defense genes through Nrf-2 axis and independently of the classic cardioprotective signaling pathways (RISK, cGMP/PKG, SAFE). © 2021 Elsevier Inc.
Συγγραφείς:
Tsoumani, M.
Georgoulis, A.
Nikolaou, P.-E.
Kostopoulos, I.V.
Dermintzoglou, T.
Papatheodorou, I.
Zoga, A.
Efentakis, P.
Konstantinou, M.
Gikas, E.
Kostomitsopoulos, N.
Papapetropoulos, A.
Lazou, A.
Skaltsounis, A.-L.
Hausenloy, D.J.
Tsitsilonis, O.
Tseti, I.
Di Lisa, F.
Iliodromitis, E.K.
Andreadou, I.
Περιοδικό:
FREE RADICAL BIOLOGY AND MEDICINE
Εκδότης:
W B SAUNDERS CO-ELSEVIER INC
Λέξεις-κλειδιά:
calcium; cyclic GMP; n benzyl 2 cyano 3 (3,4 dihydroxyphenyl)acrylamide; n(g) nitroarginine methyl ester; oleuropein; transcription factor Nrf2; wortmannin; iridoid; oleuropein, acute drug administration; animal cell; animal experiment; animal model; animal tissue; antiinflammatory activity; antioxidant activity; aortic smooth muscle cell; Article; bolus injection; cell infiltration; cell population; cell viability; controlled study; drug blood level; drug mechanism; experimental rabbit; heart infarction; heart infarction size; heart protection; in vivo study; ischemic postconditioning; male; mitochondrial permeability; monocyte; mouse; myocardial ischemia reperfusion injury; nonhuman; oxidative defense; priority journal; protein expression; rat; signal transduction; single drug dose; synergistic effect; animal; Leporidae; myocardial ischemia reperfusion injury; olive tree; oxidative stress, Animals; Iridoid Glucosides; Ischemic Postconditioning; Mice; Myocardial Reperfusion Injury; Olea; Oxidative Stress; Rabbits
DOI:
10.1016/j.freeradbiomed.2021.02.011
