Identification Of Low Molecular Weight Metabolites That Can Predict Low Dose Aspirin Induced Gastric Toxicity And Resistance In Rats And Stable Coronary Artery Disease Patients Using Nmr-Based Pharmacometabonomics

Low Dose Aspirin (LDA) is the cornerstone of secondary prevention in coronary artery disease (CAD). Despite its established efficacy, it suffers a major setback of causing gastrointestinal toxicity. In addition, some patients still experience atherothrombotic events while on aspirin secondary prophy...

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Main Author: Abubakar, Sha’aban
Format: Thesis
Language:English
Published: 2019
Subjects:
Online Access:http://eprints.usm.my/46590/1/Abubakar_20062019_24.pdf
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author Abubakar, Sha’aban
author_facet Abubakar, Sha’aban
author_sort Abubakar, Sha’aban
collection USM
description Low Dose Aspirin (LDA) is the cornerstone of secondary prevention in coronary artery disease (CAD). Despite its established efficacy, it suffers a major setback of causing gastrointestinal toxicity. In addition, some patients still experience atherothrombotic events while on aspirin secondary prophylaxis, a term known as aspirin resistance. The reasons why some people experience its serious gastric toxicity while others do not is still poorly understood. Likewise, the reason why some patients are adequately protected from a secondary event while others experience another event is yet to be adequately understood. The aim of this project was to evaluate the use of pharmacometabonomics, in finding novel metabolites that can predict aspirin-induced gastric toxicity and aspirin resistance in rats. It also aimed at validating such metabolites in CAD patients. The study involved 2 phases, namely the discovery phase in rats and the validation phase in humans. Pre-dose models were developed using H-NMR spectroscopic data from the biofluids of Sprague Dawley (SD) rats and the respective class identities of the rats. The data were initially subjected to multivariate statistical analysis including principal component analysis and orthogonal-partial least square discriminant analysis. The class identities were either gastric toxic versus non-gastric toxic or aspirin resistant versus aspirin sensitive for the gastric toxicity and aspirin resistance studies respectively.
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spelling usm.eprints-465902020-06-22T02:17:51Z http://eprints.usm.my/46590/ Identification Of Low Molecular Weight Metabolites That Can Predict Low Dose Aspirin Induced Gastric Toxicity And Resistance In Rats And Stable Coronary Artery Disease Patients Using Nmr-Based Pharmacometabonomics Abubakar, Sha’aban RS1-441 Pharmacy and materia medica Low Dose Aspirin (LDA) is the cornerstone of secondary prevention in coronary artery disease (CAD). Despite its established efficacy, it suffers a major setback of causing gastrointestinal toxicity. In addition, some patients still experience atherothrombotic events while on aspirin secondary prophylaxis, a term known as aspirin resistance. The reasons why some people experience its serious gastric toxicity while others do not is still poorly understood. Likewise, the reason why some patients are adequately protected from a secondary event while others experience another event is yet to be adequately understood. The aim of this project was to evaluate the use of pharmacometabonomics, in finding novel metabolites that can predict aspirin-induced gastric toxicity and aspirin resistance in rats. It also aimed at validating such metabolites in CAD patients. The study involved 2 phases, namely the discovery phase in rats and the validation phase in humans. Pre-dose models were developed using H-NMR spectroscopic data from the biofluids of Sprague Dawley (SD) rats and the respective class identities of the rats. The data were initially subjected to multivariate statistical analysis including principal component analysis and orthogonal-partial least square discriminant analysis. The class identities were either gastric toxic versus non-gastric toxic or aspirin resistant versus aspirin sensitive for the gastric toxicity and aspirin resistance studies respectively. 2019-06 Thesis NonPeerReviewed application/pdf en http://eprints.usm.my/46590/1/Abubakar_20062019_24.pdf Abubakar, Sha’aban (2019) Identification Of Low Molecular Weight Metabolites That Can Predict Low Dose Aspirin Induced Gastric Toxicity And Resistance In Rats And Stable Coronary Artery Disease Patients Using Nmr-Based Pharmacometabonomics. PhD thesis, Universiti Sains Malaysia.
spellingShingle RS1-441 Pharmacy and materia medica
Abubakar, Sha’aban
Identification Of Low Molecular Weight Metabolites That Can Predict Low Dose Aspirin Induced Gastric Toxicity And Resistance In Rats And Stable Coronary Artery Disease Patients Using Nmr-Based Pharmacometabonomics
title Identification Of Low Molecular Weight Metabolites That Can Predict Low Dose Aspirin Induced Gastric Toxicity And Resistance In Rats And Stable Coronary Artery Disease Patients Using Nmr-Based Pharmacometabonomics
title_full Identification Of Low Molecular Weight Metabolites That Can Predict Low Dose Aspirin Induced Gastric Toxicity And Resistance In Rats And Stable Coronary Artery Disease Patients Using Nmr-Based Pharmacometabonomics
title_fullStr Identification Of Low Molecular Weight Metabolites That Can Predict Low Dose Aspirin Induced Gastric Toxicity And Resistance In Rats And Stable Coronary Artery Disease Patients Using Nmr-Based Pharmacometabonomics
title_full_unstemmed Identification Of Low Molecular Weight Metabolites That Can Predict Low Dose Aspirin Induced Gastric Toxicity And Resistance In Rats And Stable Coronary Artery Disease Patients Using Nmr-Based Pharmacometabonomics
title_short Identification Of Low Molecular Weight Metabolites That Can Predict Low Dose Aspirin Induced Gastric Toxicity And Resistance In Rats And Stable Coronary Artery Disease Patients Using Nmr-Based Pharmacometabonomics
title_sort identification of low molecular weight metabolites that can predict low dose aspirin induced gastric toxicity and resistance in rats and stable coronary artery disease patients using nmr based pharmacometabonomics
topic RS1-441 Pharmacy and materia medica
url http://eprints.usm.my/46590/1/Abubakar_20062019_24.pdf
work_keys_str_mv AT abubakarshaaban identificationoflowmolecularweightmetabolitesthatcanpredictlowdoseaspirininducedgastrictoxicityandresistanceinratsandstablecoronaryarterydiseasepatientsusingnmrbasedpharmacometabonomics