Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Prediction of Low-Dose Aspirin-Induced Gastric Toxicity Using Nuclear Magnetic Resonance Spectroscopy-Based Pharmacometabolomics in Rats

Version 1 : Received: 27 January 2022 / Approved: 31 January 2022 / Online: 31 January 2022 (17:26:48 CET)

A peer-reviewed article of this Preprint also exists.

Sha’aban, A.; Zainal, H.; Khalil, N.A.; Abd Aziz, F.; Ch’ng, E.S.; Teh, C.-H.; Mohammed, M.; Ibrahim, B. Prediction of Low-Dose Aspirin-Induced Gastric Toxicity Using Nuclear Magnetic Resonance Spectroscopy-Based Pharmacometabolomics in Rats. Molecules 2022, 27, 2126. Sha’aban, A.; Zainal, H.; Khalil, N.A.; Abd Aziz, F.; Ch’ng, E.S.; Teh, C.-H.; Mohammed, M.; Ibrahim, B. Prediction of Low-Dose Aspirin-Induced Gastric Toxicity Using Nuclear Magnetic Resonance Spectroscopy-Based Pharmacometabolomics in Rats. Molecules 2022, 27, 2126.

Journal reference: Molecules 2022, 27, 2126
DOI: 10.3390/molecules27072126

Abstract

Background: Low-dose aspirin (LDA) is the backbone for secondary prevention of coronary artery disease, though limited by gastric toxicity. This study was 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 identify 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 a near-perfect reproducibility, 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.

Keywords

aspirin; pharmacometabolomic; nuclear magnetic resonance; spectroscopy; gastric toxicity; multivariate analysis

Subject

MEDICINE & PHARMACOLOGY, Pharmacology & Toxicology

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