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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...

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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: 2020
Subjects:
RA Public aspects of medicine
Online Access:https://eprints.ums.edu.my/id/eprint/25667/1/Tocotrienol-rich%20fraction%20modulates%20cardiac%20metabolic%20profile%20changes%20in%20isoprenaline-induced%20myocardial%20infarction%20rats.pdf
https://eprints.ums.edu.my/id/eprint/25667/
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spelling my.ums.eprints.256672021-04-08T14:03:11Z https://eprints.ums.edu.my/id/eprint/25667/ 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 RA Public aspects of medicine 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 ultrahigh-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, R2 Y>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. 2020 Article PeerReviewed text en https://eprints.ums.edu.my/id/eprint/25667/1/Tocotrienol-rich%20fraction%20modulates%20cardiac%20metabolic%20profile%20changes%20in%20isoprenaline-induced%20myocardial%20infarction%20rats.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. 10.17576/jsm-2020-4902-14
institution Universiti Malaysia Sabah
building UMS Library
collection Institutional Repository
continent Asia
country Malaysia
content_provider Universiti Malaysia Sabah
content_source UMS Institutional Repository
url_provider http://eprints.ums.edu.my/
language English
topic RA Public aspects of medicine
spellingShingle RA Public aspects of medicine
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
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 ultrahigh-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, R2 Y>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
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
publishDate 2020
url https://eprints.ums.edu.my/id/eprint/25667/1/Tocotrienol-rich%20fraction%20modulates%20cardiac%20metabolic%20profile%20changes%20in%20isoprenaline-induced%20myocardial%20infarction%20rats.pdf
https://eprints.ums.edu.my/id/eprint/25667/
_version_ 1760230397941121024
score 13.239859

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