Submitted on October 15, 2007
Accepted on December 10, 2007
CARDIOPROTECTION WITH PALM OIL TOCOTRIENOLS: COMPARISION OF DIFFERENT ISOMERS
Samarjit Das1, Istvan Lekli1, Manika Das1, Gergo Szabo2, Judit Varadi2, Bela Juhasz2, Istvan Bak2, Kalanithi Nesaretam3, Arpad Tosaki2, Saul R Powell4, and Dipak K. Das5*
1 Cardiovascular Research Center, University of Connecticut School of Medicine, Farmington, Connecticut, United States
2 Pharmacy, University of Debrecen, Debrecen, Hungary
3 Board, Malaysian Palm Oil Board, Kuala Lumpur, Malaysia
4 Medicine, Feinstein Institute for Medical research, New Hyde Park, New York, United States
5 Department of Surgery, University of Connecticut School of Medicine, Farmington, Connecticut, United States
* To whom correspondence should be addressed. E-mail: ddas{at}neuron.uchc.edu.
A recent study from our laboratory indicated the cardioprotective ability of tocotrienol rich factor (TRF) from the red palm oil. The present study compared cardioprotective abilities of different isomers of tocotrienols against TRF. The rats were randomly assigned to one of the five groups: The animals were given by gavaging either 3.5% of TRF or one of the isomers of tocotrienols, 
, 
or 
while the control animals were given (by gavaging) vehicle only. After 4 weeks, the rats were sacrificed and the hearts were then subjected to 30 min of global ischemia followed by 2 h of reperfusion. Dose-response and time-response studies revealed optimal concentration for TRF as 3.5% TRF and 0.3 mg/kg body wteight of tocotrienol isoforms given for 4 weeks. TRF as well as all the isomers of tocotrienol used in our study provided cardioprotection as evidenced by their ability to improve postischemic ventricular functions, improve electrical rhythm disturbances and to reduce myocardial infarct size. -isoform tocotrienol was the most cardioprotective of all the isomers followed by - and -. The molecular mechanisms of cardioprotection afforded by tocotrienols were probed by evaluating their respective abilities to stabilize proteasome allowing it to maintain a balance between pro-death and pro-survival signals. Our results demonstrated that tocotrienols diminished c-Src but increased phosphorylation of Akt thus generating a survival signal.
