Dharaniyambigai, KUBERAPANDIAN and Victor Arokia Doss, D (2021) Identification Of Serum Metabolites As Early Predictors Of Doxorubicin Induced Cardiac Hypertrophy. Journal of Cardiovascular Disease Research, 12 (3). pp. 992-1003. ISSN 0975-3583

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Abstract

Background: Cardiac hypertrophy (CH) is the asymptomatic enlargement of cardiac ventricles
induced during doxorubicin (DOX) administration and the lack of its early detection imposes survival
risk.
Objectives: This study on the seven diagnostic parameters of CH comorbidities, QRS complex, Ramplitude, R-R interval and heart rate (HR) of ECG, 3-hydroxybutyrate (3-HB), lactic acid (LA), urea
as the responders of metabolic shifts in DOX induced CH for which the early identification of serum
predictors and their putatively affected pathways were attempted.
Methods: Male Sprague Dawley rats (n=5) were administered DOX (2.5 mg/kg, i.p, 2 weeks, every 5th
day). Cardiotoxicity was evaluated using electrocardiography (ECG), heart weight (HW)/body weight
(BW) ratio and histopathological analysis. Gas chromatography mass spectrometry (GC-MS) analysis
was performed to screen the serum metabolites. Pearson’s correlation followed by multiple regression
analysis (MRA) identified strongly significant predictor metabolites. Significantly affected pathways
were identified using Metabolite set enrichment analysis (MSEA). All the data were verified
statistically (P<0.05).
Results: DOX administered rats exhibited CH commencement whose serum metabolite analysis using
GC-MS, correlation, MRA identified sorbitol as the significant early predictor for R-amplitude,
isoleucine for R-R interval, mannonic acid for HR, cholesterol for 3-HB, succinic acid for LA and urea.
No significant relationship or predictor were identified for QRS complex. MSEA mapped branched
chain amino acid (BCAA) degradation and ketone body metabolism as the highly impactable
significant pathways by the significant 5 predictors.
Conclusion: This study identified significant predictors and pathways that can aid in early detection
and intervention of CH induced by DOX.

Item Type: Article
Uncontrolled Keywords: Doxorubicin, cardiac hypertrophy, early predictors, GC-MS, correlation, regression
Depositing User: Mr Team Mosys
Date Deposited: 12 Aug 2022 04:20
Last Modified: 12 Aug 2022 04:20
URI: http://ir.psgcas.ac.in/id/eprint/1447

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