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Troxerutin reverses fibrotic changes in the myocardium of high-fat high-fructose diet-fed mice

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Abstract

A previous study from our laboratory showed that troxerutin (TX) provides cardioprotection by mitigating lipid abnormalities in a high-fat high-fructose diet (HFFD)-fed mice model of metabolic syndrome (MS). The present study aims to investigate the reversal effect of TX on the fibrogenic changes in the myocardium of HFFD-fed mice. Adult male Mus musculus mice were grouped into four and fed either control diet or HFFD for 60 days. Each group was divided into two, and the mice were either treated or untreated with TX (150 mg/kg bw, p.o) from the 16th day. HFFD-fed mice showed marked changes in the electrocardiographic data. Increased levels of myocardial superoxide, p22phox subunit of NADPH oxidase, transforming growth factor (TGF), smooth muscle actin (α-SMA), and matrix metalloproteinases (MMPs)-9 and -2, and decreased levels of tissue inhibitors of MMPs-1 and -2 were observed. Furthermore, degradation products of troponin I and myosin light chain-1 were observed in the myocardium by immunoblotting. Rise in collagen was observed by hydroxyproline assay, while fibrotic changes were noticed by histology and Western blotting. Hypertrophy of cardiomyocytes and myocardial calcium accumulation were also observed in HFFD-fed mice. TX treatment exerted cardioprotective and anti-fibrotic effects in HFFD-fed mice by improving cardiac contractile function, reducing superoxide production and by favorably modifying the fibrosis markers. These findings suggest that TX could be cardioprotective through its antioxidant and antifibrogenic actions. This new finding could pave way for translation studies to human MS.

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Acknowledgments

The first author Rajagopalan Geetha is thankful to the Indian Council of Medical Research (ICMR), New Delhi for awarding Senior Research Fellowship (SRF) to carry out this work.

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Authors and Affiliations

  1. Department of Biochemistry and Biotechnology, Annamalai University, Annamalai Nagar, Chidambaram, 608 002, Tamil Nadu, India

    Rajagopalan Geetha, Mutulur Krishnamoorthy Radika, Emayavaramban Priyadarshini & Carani Venkatraman Anuradha

  2. Department of Pathology, Mahatma Gandhi Medical College and Research Institute, Puducherry, India

    Krishnamurthy Bhavani

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  1. Rajagopalan Geetha
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  2. Mutulur Krishnamoorthy Radika
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Correspondence to Carani Venkatraman Anuradha.

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Geetha, R., Radika, M.K., Priyadarshini, E. et al. Troxerutin reverses fibrotic changes in the myocardium of high-fat high-fructose diet-fed mice. Mol Cell Biochem 407, 263–279 (2015). https://doi.org/10.1007/s11010-015-2474-3

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