Prediction of low-dose aspirin-induced gastric toxicity using nuclear magnetic resonance spectroscopy-based pharmacometabolomics in rats

Sha'aban, Abubakar ORCID: https://orcid.org/0000-0002-5491-9851, Zainal, Hadzliana, Khalil, Nor Azlina, Abd Aziz, Fatimatuzzahra', Ch'ng, Ewe Seng, Teh, Chin-Hoe, Mohammed, Mustapha and Ibrahim, Baharudin 2022. Prediction of low-dose aspirin-induced gastric toxicity using nuclear magnetic resonance spectroscopy-based pharmacometabolomics in rats. Molecules 27 (7) , 2126. 10.3390/molecules27072126

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Abstract

Background: Low-dose aspirin (LDA) is the backbone for secondary prevention of coronary artery disease, although limited by gastric toxicity. This study aimed to identify novel metabolites that could predict LDA-induced gastric toxicity using pharmacometabolomics. Methods: Pre-dosed urine samples were collected from male Sprague-Dawley rats. The rats were treated with either LDA (10 mg/kg) or 1% methylcellulose (10 mL/kg) per oral for 28 days. The rats’ stomachs were examined for gastric toxicity using a stereomicroscope. The urine samples were analyzed using a proton nuclear magnetic resonance spectroscopy. Metabolites were systematically identified by exploring established databases and multivariate analyses to determine the spectral pattern of metabolites related to LDA-induced gastric toxicity. Results: Treatment with LDA resulted in gastric toxicity in 20/32 rats (62.5%). The orthogonal projections to latent structures discriminant analysis (OPLS-DA) model displayed a goodness-of-fit (R2Y) value of 0.947, suggesting near-perfect reproducibility and a goodness-of-prediction (Q2Y) of −0.185 with perfect sensitivity, specificity and accuracy (100%). Furthermore, the area under the receiver operating characteristic (AUROC) displayed was 1. The final OPLS-DA model had an R2Y value of 0.726 and Q2Y of 0.142 with sensitivity (100%), specificity (95.0%) and accuracy (96.9%). Citrate, hippurate, methylamine, trimethylamine N-oxide and alpha-keto-glutarate were identified as the possible metabolites implicated in the LDA-induced gastric toxicity. Conclusion: The study identified metabolic signatures that correlated with the development of a low-dose Aspirin-induced gastric toxicity in rats. This pharmacometabolomic approach could further be validated to predict LDA-induced gastric toxicity in patients with coronary artery disease.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Additional Information:	This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).
Publisher:	MDPI
ISSN:	1420-3049
Date of First Compliant Deposit:	24 August 2022
Date of Acceptance:	22 March 2022
Last Modified:	20 May 2023 02:10
URI:	https://orca.cardiff.ac.uk/id/eprint/151932

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