Victor Arokia Doss, D (2021) Identification of serum predictors of n-acetyl-l-cysteine and isoproterenol induced remodelling in cardiac hypertrophy. Turkish Journal of Biology, 45 (3): 8. pp. 1-11. ISSN 1303-6092

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Abstract

Cardiac hypertrophy (CH), leading to cardiac failure is due to chronic metabolic alterations occurring during cellular stress.
Besides the already known relationship between oxidative stress and CH, there are implications of reductive stress leading to CH.
This study attempted to develop reductive stress-based CH rat model using n-acetyl-L-cysteine (NAC), a glutathione agonist that was
compared with typical isoproterenol (ISO) induced CH model. The main objective was to identify serum metabolites that can serve
as potent predictors for seven routine clinical and diagnostic parameters in CH: 3-hydroxybutyrate (3-HB), lactic acid (LA), urea, and
ECG-CH parameters (QRS complex, R-amplitude, R-R interval, heart rate) that were hypothesized to underlie metabolic remodelling in
this study. CH was assessed using electrocardiography, hypertrophic index and histopathological analysis (H&E stain) in both ventricles
after 2 weeks. Gas chromatography mass spectroscopy analysis (GC-MS) identified unique metabolite finger-prints. Correlation and
pattern analysis revealed strong relationships between specific metabolites and parameters (Pearson’s score > 0.7) of this study. Multiple
regression analysis (MRA) for the strongly related metabolites (independent variables) with each of the seven parameters (dependent
variables) identified significant predictors for the latter namely fructose, valine, butanoic acid in NAC and cholesterol, erythrose,
isoleucine in ISO models, with proline and succinic acid as common for both models. Metabolite set enrichment analysis (MSEA)
of those significant predictors (p < 0.05) mapped butyrate metabolism as highly influential pathway in NAC, with arginine-proline
metabolism and branched chain amino acid (BCAA) degradation as common pathways in both models, thus providing new insights
towards initial metabolic remodeling in the pathogenesis of CH.

Item Type: Article
Uncontrolled Keywords: Cardiac hypertrophy, serum predictors, reductive stress, metabolic remodeling, n-acetyl-L-cysteine, isoproterenol
Depositing User: Mr Team Mosys
Date Deposited: 03 May 2023 05:08
Last Modified: 03 May 2023 05:08
URI: http://ir.psgcas.ac.in/id/eprint/1891

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