Abstract
The aim of this study was to investigate the changes caused by anabolic androgenic steroids (methandienone) in the hypothalamic adrenal axis (HPA) and oxidative status in adrenal glands and a protective role role by using organic selenium (high-selenium yeast) in adult male rabbits which treated with Methandienone in combination with selenium. A total of 20 intact male rabbits were divided into four equal groups (n = 5 for each group):a control group receiving distilled water, the AAS group (T1) receiving Methandienone (oral dose of 0.35 mg / kg.B.W.),the selenium group (T2) receiving high-selenium yeast (3 μg/ kg B.W orally)and the combination group (T3) getting both methandienone and selenium. The dosing every day for 60 days. . The hormones β-endorphin, ACTH and cortisone were measured in serum during two periods, 30 and 60 days of the experiment and the expression levels of Nuclear factor erythroid-2 and related factor-2 (Nrf2) and Translocater protein (TSPO) genes were measured in adrenal gland. a significant increase in beta-endorphin and ACTH and a decrease in cortisone were found in both 30 and 60 day periods in the AAS group (T1) compared with another groups (control, T2 and T3). On the other hand, T3 group shows a decrease in serum β-Endorphin and ACTH and no significant changes in cortisone in both periods .These changes were a compared with to AAS group. Moreover, there is a significant increased in revers transcription (mRNA) of Nrf2 factor and TSPO genes in AAS group(T1) as compared with other groups (T2 and T3). In addition, we observed a significant decrease in levels of Nrf2 and TSPO mRNA in the selenium-yeast group compared to the AAS group (T1). In conclusion, these results showed that organic selenium (high selenium yeast) has a positive effect (protective role) against oxidative damage to the adrenal gland caused by AAS with no effect on the adrenal steroidogenesis, which are affected by AAS.
Highlights
Anabolic- androgenic steroids (AASs) are synthetic derivatives of testosterone
A little information about effect of AAS on adrenal steroidogenesis and oxidative status, this study focusing on HPA axis and molecular bioactive markers,which involved Nuclear factor erythroid2 and related factor-2 (Nrf2) and Translocator protein (TSPO) genes in adrenal tissues.AAS can compete for binding to glucocorticoid receptors, and this competition has been reported to induce anabolic effects by reducing glucocorticoid-induced catabolism [8]
The transcription factor (Nrf2) is an important protective factor in the cell against the negative effects associated with oxidative stress, which regulates the detoxifying and antioxidant protective genes expression in the cell by attaching to the antioxidant response element (ARE) in the nucleus and increased expression of its target genes [9].Translocator protein (TSPO) is a transmembrane protein that resides in the outer membrane of mitochondria and is expressed primarily in steroid tissues and the brain, It has the function of translocating cholesterol from the outer to the inner mitochondrial membrane, which is stimulated by steroidogenesis, and TSPO expression is increased with brain damage and neurodegeneration, so consider a sensitive biomarker of brain function, As well as,it contributed in redox homeostasis [10]
Summary
Anabolic- androgenic steroids (AASs) are synthetic derivatives of testosterone. For decades, it has been used to treat short stature condition, burns, wasting signs, osteoporosis, and severe anemia [1].In the current study used methandienone, commercially known (dianabol), which is a third class of AAS characterized by the addition of an alkyl group to 17 carbon atoms [2]. A little information about effect of AAS on adrenal steroidogenesis and oxidative status, this study focusing on HPA axis and molecular bioactive markers,which involved Nrf and TSPO genes in adrenal tissues.AAS can compete for binding to glucocorticoid receptors, and this competition has been reported to induce anabolic effects by reducing glucocorticoid-induced catabolism [8]. The transcription factor (Nrf2) is an important protective factor in the cell against the negative effects associated with oxidative stress, which regulates the detoxifying and antioxidant protective genes expression in the cell by attaching to the antioxidant response element (ARE) in the nucleus and increased expression of its target genes [9].Translocator protein (TSPO) is a transmembrane protein that resides in the outer membrane of mitochondria and is expressed primarily in steroid tissues and the brain, It has the function of translocating cholesterol from the outer to the inner mitochondrial membrane, which is stimulated by steroidogenesis, and TSPO expression is increased with brain damage and neurodegeneration, so consider a sensitive biomarker of brain function, As well as,it contributed in redox homeostasis [10]
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