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Identification of serum predictors of n-acetyl-l-cysteine and isoproterenol induced remodelling in cardiac hypertrophy

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. | Turkish Journal of Biology Turk J Biol 2021 45 323-332 http journals.tubitak.gov.tr biology TÜBİTAK Research Article doi 10.3906 biy-2101-56 Identification of serum predictors of n-acetyl-l-cysteine and isoproterenol induced remodelling in cardiac hypertrophy Dharaniyambigai KUBERAPANDIAN Victor Arokia DOSS Department of Biochemistry PSG College of Arts amp Science Coimbatore Tamil Nadu India Received 27.01.2021 Accepted Published Online 04.05.2021 Final Version 23.06.2021 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 amp 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 gt 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. .