Reactive oxygen species: players in the cardiovascular effects of testosterone

Abstract

Tostes RC, Carneiro FS, Carvalho MH, Reckelhoff JF. Reactive oxygen species: players in the cardiovascular effects of testosterone. Am J Physiol Regul Integr Comp Physiol 310: R1-R14, 2016. First published November 4, 2015 doi:10.1152/ajpregu.00392.2014.-Androgens are essential for the development and maintenance of male reproductive tissues and sexual function and for overall health and well being. Testosterone, the predominant and most important androgen, not only affects the male reproductive system, but also influences the activity of many other organs. In the cardiovascular system, the actions of testosterone are still controversial, its effects ranging from protective to deleterious. While early studies showed that testosterone replacement therapy exerted beneficial effects on cardiovascular disease, some recent safety studies point to a positive association between endogenous and supraphysiological levels of androgens/testosterone and cardiovascular disease risk. Among the possible mechanisms involved in the actions of testosterone on the cardiovascular system, indirect actions (changes in the lipid profile, insulin sensitivity, and hemostatic mechanisms, modulation of the sympathetic nervous system and renin-angiotensin-aldosterone system), as well as direct actions (modulatory effects on proinflammatory enzymes, on the generation of reactive oxygen species, nitric oxide bioavailability, and on vasoconstrictor signaling pathways) have been reported. This mini-review focuses on evidence indicating that testosterone has prooxidative actions that may contribute to its deleterious actions in the cardiovascular system. The controversial effects of testosterone on ROS generation and oxidant status, both prooxidant and antioxidant, in the cardiovascular system and in cells and tissues of other systems are reviewed. cardiovascular; prooxidant; antioxidant TESTOSTERONE 1 IS THE PREDOMINANT and most important androgen, playing a major role in the development of male reproductive tissues (130,135). "Androgen" is a broad term for any natural or synthetic compound that primarily influences the growth and development of the male reproductive system, including the activity of the accessory male sex organs and development of male secondary sex characteristics (21, 135). Androgens are also essential for health and well being, and their beneficial and stimulant effects have been known for a long time, since the seminal studies from Brown-Séquard in the nineteenth century 2 (22, 135): "ь ь ь in the seminal fluid, as secreted by the testicles, a substance or several substances exist which, entering the blood by resorption, have a most essential use in giving strength to the nervous system and to other parts ь ь ь ."Other androgens include androstenedione, 5␣-dihydrotestosterone (DHT), which is produced from testosterone by the enzyme 5␣-reductase, dehydroepiandrosterone (DHEA), DHEA sulfate (DHEA-S), and synthetic androgens in their many steroid ester variations (e.g., testosterone cypionate, decanoate, undecanoate, enant...

Effects of Supraphysiological Doses of Anabolic Androgenic Steroids on the Left Ventricles of Male and Female Mice Submitted to Swimming

“…Differences between genders are often ignored and underestimated when studying the cardiovascular system, and these cause biases and losses in the performed researches. 10 However, previous clinical and epidemiological studies have corroborated and acknowledged gender differences in cardiovascular function and disease. 11 The causal link between the use of AAS and the occurrence of cardiovascular diseases has been increasingly evidenced through researches, which demonstrate the frequent use of these substances associated with the rise in the occurrence of death due to cardiac arrest among the users.…”

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“…In vivo, the free radicals have a very reactive with lipid, protein, and DNA (Bhattacharya, 2015) to create a stable compound. Thus, excess of free radicals can seriously damage essential macromolecules of the cell and theirs implicated in many major diseases include cancer (Hecht et al, 2016), cardiovascular diseases (Tostes, Carneiro, Carvalho, & Reckelhoff, 2016), inflammatory diseases (Rimessi, Previati, Nigro, Wieckowski, & Pinton, 2016), heart diseases (Sverdlov et al, 2016), respiratory diseases (Guo et al, 2017), diabetes (Onoue et al, 2016), neurological diseases (Radak et al, 2016), aging process (Park, Sim, Lee, Sung, & Oh, 2016), etc. However, the human body has various mechanisms to counteract free radical by producing antioxidant: (a) enzymatic antioxidant i.e.…”