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This Article Full Text Full Text (PDF) All Versions of this Article: 294/3/H1365    most recent 01005.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Juhasz, B. Articles by Maulik, N. Search for Related Content PubMed PubMed Citation Articles by Juhasz, B. Articles by Maulik, N.

Bromelain induces cardioprotection against ischemia-reperfusion injury through Akt/FOXO pathway in rat myocardium

¹Department of Surgery, Molecular Cardiology and Angiogenesis Laboratory, and ²Department of Immunology, University of Connecticut Health Center, Farmington, Connecticut; ³Department of Food Technology and Biochemical Engineering, Jadavpur University, Calcutta, India; ⁴Department of Biochemistry and Biotechnology, Annamalai University, Tamil Nadu, India; ⁵Kansai Medical University, School of Medicine, Osaka, Japan; ⁶Department of Pharmacology, University of Debrecen, Debrecen, Hungary

Submitted 30 August 2007 ; accepted in final form 11 January 2008

Bromelain (Br), a proteolytic enzyme extracted from the stem of the pineapple, is known to possess anti-inflammatory activity and has been shown to reduce blood viscosity, prevent the aggregation of blood platelets, and improve ischemia-reperfusion (I/R) injury in a skeletal muscle model. We investigated the capacity of Br to limit myocardial injury in a global I/R model. Adult male Sprague-Dawley rats were divided into two groups: control (PBS) and Br at 10 mg/kg in PBS administered via intraperitoneal injection (twice/day) for 15 consecutive days. On day 16, the hearts were excised and subjected to 30 min of global ischemia followed by 2 h of reperfusion. Br treatment showed higher left ventricular functional recovery throughout reperfusion compared with the controls [maximum rate of rise in intraventricular pressure (dP/dt_max), 2,225 vs. 1,578 mmHg/s at 2 h reperfusion]. Aortic flow was also found to be increased in Br treatment when compared with that in untreated rats (11 vs. 1 ml). Furthermore, Br treatment reduced both the infarct size (34% vs. 43%) and the degree of apoptosis (28% vs. 37%) compared with the control animals. Western blot analysis showed an increased phosphorylation of both Akt and FOXO3A in the treatment group compared with the control. These results demonstrated for the first time that Br triggers an Akt-dependent survival pathway in the heart, revealing a novel mechanism of cardioprotective action and a potential therapeutic target against I/R injury.

apoptosis; myocardial infarction; Ananas comosus; forkhead transcription factor