Bromelain induces cardioprotection against ischemia-reperfusion injury through Akt/FOXO pathway in rat myocardium.
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.
Juhasz
Bela
B
Department of Surgery, Molecular Cardiology and Angiogenesis Laboratory, University of Connecticut Health Center, Farmington, CT 06030-1110, USA.
Thirunavukkarasu
Mahesh
M
Pant
Rima
R
Zhan
Lijun
L
Penumathsa
Suresh Varma
SV
Secor
Eric R
ER
Srivastava
Sapna
S
Raychaudhuri
Utpal
U
Menon
Venugopal P
VP
Otani
Hajime
H
Thrall
Roger S
RS
Maulik
Nilanjana
N
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D001963:Bromelains / Q000627:therapeutic use*; D002316:Cardiotonic Agents; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology; D003600:Cytosol / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000502:physiology*; D006334:Heart Function Tests; D006339:Heart Rate / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology / Q000517:prevention & control; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology*; D016277:Ventricular Function, Left / Q000502:physiology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002316:Cardiotonic Agents; D051858:Forkhead Transcription Factors; D009687:Nuclear Proteins; D001963:Bromelains; D051057:Proto-Oncogene Proteins c-akt