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Combination of exercise training and l-arginine reverses aging process through suppression of oxidative stress, inflammation, and apoptosis in the rat heart

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Abstract

Aging-induced progressive decline of molecular and metabolic factors in the myocardium is suggested to be related with heart dysfunction and cardiovascular disease. Therefore, we evaluated the effects of exercise training and l-arginine supplementation on oxidative stress, inflammation, and apoptosis in ventricle of the aging rat heart. Twenty-four 24-month-aged Wistar rats were randomly divided into four groups: the aged control, aged exercise, aged l-arginine (orally administered with 150 mg/kg for 12 weeks), and aged exercise + l-arginine groups. Six 4-month-old rats were also considered the young control. Animals with training program performed exercise on a treadmill 5 days/week for 12 weeks. After 12 weeks, protein levels of Bax, Bcl-2, pro-caspase-3/cleaved caspase-3, cytochrome C, and heat shock protein (HSP)-70 were assessed. Tissue contents of total anti-oxidant capacity, superoxide dismutase, catalase, and levels of tumor necrosis factor alpha (TNF-α), interleukin (IL)-1β, and IL-6 were analyzed. Histological and fibrotic changes were also evaluated. Treadmill exercise and l-arginine supplementation significantly alleviated aging-induced apoptosis with enhancing HSP-70 expression, increasing anti-oxidant enzyme activity, and suppressing inflammatory markers in the cardiac myocytes. Potent attenuation in apoptosis, inflammation, and oxidative stress was indicated in the rats with the combination of l-arginine supplementation and exercise program in comparison with each group (p < 0.05). In addition, fibrosis percentage and collagen accumulation were significantly lower in the rats with the combination treatment of l-arginine and exercise (p < 0.05). Treadmill exercise and l-arginine supplementation provided protection against age-induced increase in the myocyte loss and formation of fibrosis in the ventricle through potent suppression of oxidative stress, inflammations, and apoptosis pathways.

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Funding

This study was supported by the Research Council of Urmia University of Medical Sciences.

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Authors and Affiliations

  1. Student Research Committee, Urmia University of Medical Sciences, Urmia, Iran

    Saber Ghazizadeh Darband

  2. Department of Exercise Physiology, Faculty of Sport Sciences, Urmia University, Urmia, Iran

    Saber Ghazizadeh Darband

  3. Neurophysiology Research Center, Urmia University of Medical Sciences, Urmia, Iran

    Shirin Sadighparvar

  4. Immunology Research Center, Tabriz University of Medical Science, Tabriz, Iran

    Bahman Yousefi

  5. School of Nutrition and Dietetics, Acadia University, Wolfville, Nova Scotia, Canada

    Mojtaba Kaviani

  6. Solid Tumor Research Center, Urmia University of Medical Sciences, Urmia, Iran

    Kazhal Mobaraki & Maryam Majidinia

Authors
  1. Saber Ghazizadeh Darband
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  2. Shirin Sadighparvar
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All authors contributed equally to this work.

Corresponding author

Correspondence to Maryam Majidinia.

Ethics declarations

The protocol was performed according to the guidelines for the Care and Use of Laboratory Animals published by the US National Institutes of Health (NIH publication), and approved by the Animal Care and Use Committee at the Urmia University of Medical Sciences, Urmia, Iran (ethical code: IR.UMSU.REC.1396.434).

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This article is part of the special issue on Exercise Physiology: future opportunities and challenges in Pflügers Archiv—European Journal of Physiology

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Darband, S.G., Sadighparvar, S., Yousefi, B. et al. Combination of exercise training and l-arginine reverses aging process through suppression of oxidative stress, inflammation, and apoptosis in the rat heart. Pflugers Arch - Eur J Physiol 472, 169–178 (2020). https://doi.org/10.1007/s00424-019-02311-1

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