Cardioprotection with palm oil tocotrienols: comparision of different isomers

• Published in: American journal of physiology. Heart and circulatory physiology 2008-02, Vol.294 (2), p.H970-H978
• Main Authors: Das, Samarjit, Lekli, Istvan, Das, Manika, Szabo, Gergo, Varadi, Judit, Juhasz, Bela, Bak, Istvan, Nesaretam, Kalanithi, Tosaki, Arpad, Powell, Saul R, Das, Dipak K
• Format: Article
• Language: English
• Subjects: Animals; Antioxidants - chemistry; Antioxidants - pharmacology; Apoptosis - drug effects; Blotting, Western; Cardiotonic Agents; Chemical compounds; Comparative analysis; Dose-Response Relationship, Drug; Genes, src - genetics; Genes, src - physiology; Heart; Heart - drug effects; Heart Function Tests; Isomerism; Male; Malondialdehyde - metabolism; Myocardial Infarction - pathology; Myocardium - metabolism; Oncogene Protein v-akt - genetics; Oncogene Protein v-akt - metabolism; Palm Oil; Plant Oils - chemistry; Proteasome Endopeptidase Complex - drug effects; Rats; Rats, Sprague-Dawley; Rodents; Stroke; Studies; Tocotrienols - chemistry; Tocotrienols - pharmacology
• ISSN: 0363-6135; 1522-1539
• DOI: 10.1152/ajpheart.01200.2007

1 Cardiovascular Research Center, University of Connecticut School of Medicine, Farmington, Connecticut; 2 Department of Pharmacology, Faculty of Pharmacy, Health Science Center, University of Debrecen, Debrecen, Hungary; 3 Malaysian Palm Oil Board, Kuala Lumpur, Malaysia; and 4 Department of Medicine, The Feinstein Institute for Medical Research and Albert Einstein College of Medicine, New Hyde Park, New York Submitted 15 October 2007 ; accepted in final form 10 December 2007 A recent study from our laboratory indicated the cardioprotective ability of the tocotrienol-rich fraction (TRF) from red palm oil. The present study compared cardioprotective abilities of different isomers of tocotrienol against TRF as recently tocotrienol has been found to function as a potent neuroprotective agent against stroke. Rats were randomly assigned to one of the following groups: animals were given, by gavage, either 0.35%, 1%, or 3.5% TRF for two different periods of time (2 or 4 wk) or 0.03, 0.3, and 3 mg/kg body wt of one of the isomers of tocotrienol ( , , or ) for 4 wk; control animals were given, by gavage, vehicle only. After 2 or 4 wk, rats were killed, and their hearts were then subjected to 30 min of global ischemia followed by 2 h of reperfusion. Dose-response and time-response experiments revealed that the optimal concentration for TRF was 3.5% TRF and 0.3 mg/kg body wt of tocotrienol given for 4 wk. TRF as well as all the isomers of tocotrienol used in our study provided cardioprotection, as evidenced by their ability to improve postischemic ventricular function and reduce myocardial infarct size. The -isoform of tocotrienol was the most cardioprotective of all the isomers followed by the - and -isoforms. The molecular mechanisms of cardioprotection afforded by tocotrienol isoforms were probed by evaluating their respective abilities to stabilize the proteasome, allowing it to maintain a balance between prodeath and prosurvival signals. Our results demonstrated that tocotrienol isoforms reduced c-Src but increased the phosphorylation of Akt, thus generating a survival signal. tocotrienol-rich fraction; -tocotrienol; -tocotrienol; -tocotrienol; c-Src; Akt Address for reprint requests and other correspondence: D. K. Das, Cardiovascular Research Center, Univ. of Connecticut School of Medicine, Farmington, CT 06030-1110 (e-mail: ddas{at}neuron.uchc.edu )