Abstract

A low testosterone level contributes to the development of oxidative damages; however, the cardiovascular effects of exogenous hormone therapy are not well elucidated. The aim of our work is to study the association of the testosterone level, antioxidant/oxidant system, and anti-inflammatory status related to the heme oxygenase (HO) system. To determine the effects of testosterone, 10-week-old, and 24-month-old sham-operated and castrated male Wistar rats were used. One part of the castrated animals was daily treated with 2.5 mg/kg cyproterone acetate, while the hormone replacement therapy was performed via an i.m. injection of a dose of 8.0 mg testosterone undecanoate/kg/once a week. The plasma testosterone level, the activity of HO and myeloperoxidase (MPO) enzymes; the concentrations of the HO-1, tumor necrosis alpha (TNF-α), and cyclic guanosine monophosphate (cGMP), as well as the total level of glutathione (GSH + GSSG) were determined from the cardiac left ventricle. In accordance with the testosterone values, the aging process and castration resulted in a decrease in antioxidant HO activity, HO-1 and cGMP concentrations and in the level of GSH + GSSG, whereas the inflammatory TNF-α and MPO activity significantly increased. Testosterone therapy was able to restore the physiological values. Our results clearly show that testosterone replacement therapy increases the antioxidant status and mitigates the inflammatory parameters via the modulation of the HO system.

Highlights

  • Low testosterone level and testosterone deficiency have been associated with the incidence and progression of chronic diseases, such as metabolic syndrome [1] and cardiovascular diseases (CVDs) [2], which are the most the common cause of death worldwide

  • We can summarize that status resulted in a significant increase in the glutamic oxaloacetic transaminase (GOT) and GPT values compared to the young/fertile hormone replacement therapy was able to ameliorate the metabolic parameters, except for the cholesterol values of aged rats where testosterone treatment did not mitigate the castration-induced adverse changes

  • Our results show that testosterone deprivation caused by the aging process or surgical castration deteriorated the antioxidant status of left ventricle (LV) and resulted in higher levels of inflammatory parameters via the modulation of the heme oxygenase (HO) system

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Summary

Introduction

Low testosterone level and testosterone deficiency have been associated with the incidence and progression of chronic diseases, such as metabolic syndrome [1] and cardiovascular diseases (CVDs) [2], which are the most the common cause of death worldwide. In addition to the Antioxidants 2019, 8, 288; doi:10.3390/antiox8080288 www.mdpi.com/journal/antioxidants

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