Tocotrienol-rich fraction modulates cardiac metabolic profile changes in isoprenaline-induced myocardial infarction rats

Khairul Anwar Zarkasi, and Satirah Zainalabidin, and Tan, Jen-Kit and Nur Haleeda Hakimi, and Nur Zuliani Ramli, and Zakiah Jubri, (2020) Tocotrienol-rich fraction modulates cardiac metabolic profile changes in isoprenaline-induced myocardial infarction rats. Sains Malaysiana, 49 (2). pp. 357-373. ISSN 0126-6039


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In myocardial infarction (MI), the occurrence of energy depletion, oxidative stress, and decreased amino acids metabolism alter tissue metabolites. Evidence has shown that tocotrienol-rich fraction (TRF) prevents myocardial injury in MI. However, the protective mechanism at the metabolite level is unknown. Male Sprague-Dawley rats were grouped into control, isoprenaline (ISO)-induced MI (MI), healthy rats receiving 200 mg/kg TRF (200TRF), and MI rats receiving 200 mg/kg TRF (200TRF+MI) groups. TRF was administered via oral gavage daily for 12 weeks followed by intraperitoneal ISO injection (85 mg/kg) for two consecutive days at a 24-hour interval to induce MI. High-performance liquid chromatography was performed to analyze serum α-tocopherol and tocotrienol concentration whereas ultra-high-performance liquid chromatography-mass spectrometry was used for the untargeted metabolomic study. Serum α-tocopherol but not tocotrienol was increased in the 200TRF (p=0.121) and 200TRF+MI (p<0.05) following TRF supplementation. Multivariate analysis by Orthogonal Projections to Latent Structures Discriminant Analysis showed high predictability of the group comparison models for MI vs control and 200TRF+MI vs MI (cross-validation: Q2>0.7, R2Y>0.8, p<0.05). A total of 84 and 37 metabolites [when covariance of p≥|0.05| (magnitude) and p(corr)≥|0.5| (reliability)] were significantly different in the myocardial homogenates of MI vs control and 200TRF+MI vs MI, respectively. MI rats had reduced S-adenosylmethionine and L-cystathionine that might worsen MI by disturbing glutathione metabolism; decreased phosphoribosyl-pyrophosphate and purine salvage process that might impair DNA synthesis, and elevated glucose-6-phosphate suggesting enhanced anaerobic glycolysis possibly for rapid production of energy. Conversely, TRF supplementation reversed the impaired metabolic pathways caused by MI.

Item Type:Article
Keywords:Isoprenaline; Liquid chromatography-mass spectrometry; Metabolomics; Myocardial infarction; Tocotrienol-rich fraction
Journal:Sains Malaysiana
ID Code:14768
Deposited By: ms aida -
Deposited On:18 Jun 2020 03:42
Last Modified:22 Jun 2020 08:31

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