Conversely, elevatedsystemic oxidative stress downregulates the expression of lipoic acidsynthase, increasing the need for dietary α-lipoic acid in order toforestall retardation of aerobic energy production . The concurrent consumption of vitamin C has preventedthe inhibition of testicular antioxidant enzymes, the increase inthe formation of lipid peroxidation products and oxidized proteincarbonyls, and the suppression of testosterone synthesis commonlyobserved in laboratory animals exposed to cadmium , lead, cyclophosphamide , or arsenic 288,289. Although CCl4also reduces the testicular activities of the antioxidants, glutathione,GPx, glutathione reductase (GR), SOD, and catalase, while inhibitingLH-stimulated testosterone synthesis, these effects are prevented bythe concurrent consumption of pomegranate polyphenols .Consistent with these reports, the pomegranate polyphenol, ellagicacid, has prevented adriamycin-induced testicular lipid peroxidationand inhibition of testosterone synthesis . Dietary supplementation with pomegranate polyphenolsupregulates the expression and activities of paraoxonases 1 (PON1) and 2 (PON2) , endogenous antioxidants that buffer theintracellular (PON2) and extracellular (PON1) environments fromoxidizing conditions 187,188 and increase the systemic antioxidantcapacity and reduce systemic oxidative stress in men 140,187, . As expected, testosterone deficiency caused by aging or surgical castration resulted in a significant increase in the inflammatory processes, as shown by the elevation of the MPO activity. Similarly, in the aging groups with a lower testosterone level, the cardiac cGMP levels were significantly lower compared to the young/fertile SO rats. (A) The effects of aging, surgical castration, and testosterone replacement therapy on the cardiac HO activity (HO; expressed as nmol bilirubin/h/mg protein). To add a significant complexity to the interaction between the testosterone level and oxidative mechanisms, the HO enzyme activity and concentration as well as the inflammatory parameters are analysed in the heart. Mixed-model ANOVA was used to assess main effects of time, treatment, and their interactions for total and free testosterone, oxygen-carrying capacity, energy and macronutrient intake, energy balance, substrate oxidation, nitrogen balance, glycogen, and mRNA expressions. Mixed-model ANOVA with fat mass and fat-free mass as covariates was used to assess energy expenditure main effects of time (balance vs deficit), treatment (TEST vs PLA), and their interactions. Total body mass, fat-free mass, and fat mass were primary outcomes of the parent study (7) and are reported in this article as a change from balance to deficit. After completing the balance phase, participants were admitted to an inpatient unit at the PBRC for the 28-d controlled diet- and exercise-induced energy deficit (55% below total energy needs) phase of the study. This study included a 14-d energy balance phase, followed by a 28-d inpatient phase of controlled diet- and exercise-induced energy deficit (Fig. 1). We also hypothesized that testosterone administration would increase the transcription of energy metabolism and fat oxidation–related genes compared with placebo after 28 d of 55% energy deficit. Ponderal data from SHAM, OQT and OQT plus testosterone 12 weeks after castration and testosterone replacement therapy. As expected, castration decreased seminal vesicle weight after 12 weeks when compared to SHAM and testosterone replacement was able to restore this value. As shown in Table 1, castration of male animals for 12 weeks did not change body weight, left or right ventricle weight, demonstrating that endogenous testosterone does not affect the heart mass. Serum levels of testosterone and estrogen were measured according to the manufacturer. They found that testosterone deficiency induced oxidative stress, while exogenous testosterone ameliorated superoxide dismutase and glutathione peroxidase enzyme activities in the cardiomyocytes . It has been proven that endogenous sex hormones protect the cells form oxidative damage; however, conflicting results have been observed in connection with the potential antioxidant role of exogenous testosterone. In agreement with the HO activity results, the testosterone deficiency in aged and castrated animals resulted in a significant reduction in the HO-1 concentration compared with the young/fertile SO rats. The induction of HO-1 is considered to enhance the antioxidant capacity of cells to provide protection against oxidative stress .
