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

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 u...

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Main Authors: Khairul Anwar Zarkasi,, Satirah Zainalabidin,, Tan, Jen-Kit, Nur Haleeda Hakimi,, Nur Zuliani Ramli,, Zakiah Jubri,
Format: Article
Language:English
Published: Penerbit Universiti Kebangsaan Malaysia 2020
Online Access:http://journalarticle.ukm.my/14768/1/ARTIKEL%2014.pdf
http://journalarticle.ukm.my/14768/
http://www.ukm.my/jsm/malay_journals/jilid49bil2_2020/KandunganJilid49Bil2_2020.html
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spelling my-ukm.journal.147682020-06-22T08:31:52Z http://journalarticle.ukm.my/14768/ Tocotrienol-rich fraction modulates cardiac metabolic profile changes in isoprenaline-induced myocardial infarction rats Khairul Anwar Zarkasi, Satirah Zainalabidin, Tan, Jen-Kit Nur Haleeda Hakimi, Nur Zuliani Ramli, Zakiah Jubri, 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. Penerbit Universiti Kebangsaan Malaysia 2020-02 Article PeerReviewed application/pdf en http://journalarticle.ukm.my/14768/1/ARTIKEL%2014.pdf 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 http://www.ukm.my/jsm/malay_journals/jilid49bil2_2020/KandunganJilid49Bil2_2020.html
institution Universiti Kebangsaan Malaysia
building Tun Sri Lanang Library
collection Institutional Repository
continent Asia
country Malaysia
content_provider Universiti Kebangsaan Malaysia
content_source UKM Journal Article Repository
url_provider http://journalarticle.ukm.my/
language English
description 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.
format Article
author Khairul Anwar Zarkasi,
Satirah Zainalabidin,
Tan, Jen-Kit
Nur Haleeda Hakimi,
Nur Zuliani Ramli,
Zakiah Jubri,
spellingShingle Khairul Anwar Zarkasi,
Satirah Zainalabidin,
Tan, Jen-Kit
Nur Haleeda Hakimi,
Nur Zuliani Ramli,
Zakiah Jubri,
Tocotrienol-rich fraction modulates cardiac metabolic profile changes in isoprenaline-induced myocardial infarction rats
author_facet Khairul Anwar Zarkasi,
Satirah Zainalabidin,
Tan, Jen-Kit
Nur Haleeda Hakimi,
Nur Zuliani Ramli,
Zakiah Jubri,
author_sort Khairul Anwar Zarkasi,
title Tocotrienol-rich fraction modulates cardiac metabolic profile changes in isoprenaline-induced myocardial infarction rats
title_short Tocotrienol-rich fraction modulates cardiac metabolic profile changes in isoprenaline-induced myocardial infarction rats
title_full Tocotrienol-rich fraction modulates cardiac metabolic profile changes in isoprenaline-induced myocardial infarction rats
title_fullStr Tocotrienol-rich fraction modulates cardiac metabolic profile changes in isoprenaline-induced myocardial infarction rats
title_full_unstemmed Tocotrienol-rich fraction modulates cardiac metabolic profile changes in isoprenaline-induced myocardial infarction rats
title_sort tocotrienol-rich fraction modulates cardiac metabolic profile changes in isoprenaline-induced myocardial infarction rats
publisher Penerbit Universiti Kebangsaan Malaysia
publishDate 2020
url http://journalarticle.ukm.my/14768/1/ARTIKEL%2014.pdf
http://journalarticle.ukm.my/14768/
http://www.ukm.my/jsm/malay_journals/jilid49bil2_2020/KandunganJilid49Bil2_2020.html
_version_ 1671340601938804736
score 13.239859

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