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TOCOTRIENOLS IN CARDIOPROTECTION: ROLE OF DIFFERENT ISOMERS
Author(s) -
Das Samarjit,
Tosaki Arpad,
Juhasz Bela,
Lekli Istvan,
Varadi Judit,
Nesaretam Kalanithi,
Maulik Nilanjana,
Das Dipak K
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1112-a
Subject(s) - cardioprotection , survivin , tocotrienol , protein kinase b , chemistry , pharmacology , apoptosis , phosphorylation , ischemia , tocopherol , vitamin e , medicine , biochemistry , antioxidant
A recent study from our laboratory indicated the cardioprotective ability of tocotrienol‐rich fraction (TRF) of red palm oil obtained from Malaysian Palm Oil Company, Malaysia. Since, TRF contains four different isomers of tocotrienols as well as a‐tocopherol, we planned to identify the isomers of tocotrienol responsible for cardioprotection. Rats were gavaged with α, γ and δ isomers of tocotrienols while another group was given water only (Control). After 4 weeks, rats were sacrificed and the isolated hearts were then subjected to 30 min of global ischemia followed by 2 h of reperfusion by working mode. All the fractions provided cardioprotection as evidenced by their ability to improve postischemic ventricular function, improve electrical rhythm disturbances and reduce myocardial infarct size and cardiomyocyte apoptosis. The order of the degree of cardioprotection was γ > α > δWe further examined the molecular mechanisms of cardioprotection afforded by tocotrienols by examining the survival signal triggered by tocotrienols. The tocotrienols minimally affected the c‐Src expression, but they significantly inhibited the phosphorylation of c‐Src, again γ‐tocotrienol being the most effective. γ‐tocotrienol also induced the phosphorylation of Akt and stabilized proteasomes suggesting that this isomer of tocotrienol can reduce myocardial ischemia reperfusion injury by inhibiting c‐Src thereby stabilizing the proteasome and generating a survival signal through the activation of Akt.