Submitted on August 30, 2007
Accepted on January 11, 2008
Bromelain induces cardioprotection against ischemia reperfusion injury through Akt/Foxo pathway in rat myocardium
Bela Juhasz1, Mahesh Thirunavukkarasu2, Rima Pant2, Lijun Zhan3, SureshVarma Penumathsa2, Eric R Secor2, Sapna Srivastava2, Utpal Raychaudhuri4, Venugopal P Menon5, Hajime Otani6, Roger S Thrall7, and Nilanjana Maulik2*
1 Physiology, University of Debrasen, Hungary
2 Surgery, University of Connecticut Medical Center, Farmington, Connecticut, United States
3 surgery, University of Connecticut Medical Center, Farmington, Connecticut, United States
4 Food Technology, Jadavpur University, Kolkata, West Bengal, India
5 Biochemistry, Annamalai University, India
6 Surgery, Osaka University, Japan
7 immunology, University of Connecticut Medical Center, Farmington, Connecticut, United States
* To whom correspondence should be addressed. E-mail: nmaulik{at}neuron.uchc.edu.
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 aggregation of blood platelets, and improve ischemia reperfusion (IR) injury in a skeletal muscle model. We investigated the capacity of Br to limit myocardial injury in a global IR model. Adult male Sprague-Dawley rats were divided into 2 groups: Control (PBS) and Br at 10 mg/kg in PBS administered via i.p injection (twice/day) for 15 consecutive days. On day 16 the hearts were excised and subjected to 30min of global ischemia followed by 2hrs of reperfusion. Br treatment showed higher left ventricular functional recovery throughout reperfusion as compared to the controls (dp/dtmax2225 vs 1578mmHg/sec at 2hrs reperfusion). Aortic flow was also found to be increased in Br treatment when compared with untreated rats (11ml vs 1ml). Furthermore Br treatment reduced both infarct size (34% vs 43%) and the degree of apoptosis (28% vs 37%) as compared to the control animals. Western blot analysis showed increased phosphorylation of both Akt and Foxo-3A in the treatment group as compared to the control. These results demonstrated for the first time that Br triggers an Akt dependent survival pathway in heart revealing a novel mechanism of cardioprotective action and as a potential therapeutic target against IR injury.
