Effects of Castration and Testosterone Replacement on Antioxidant Defense System in the Rat Left Ventricle

Abstract

There is strong evidence that oxidative stress plays a key role in the pathophysiology of several cardiovascular diseases. On the other hand, the presence of specific receptors for androgens and estrogens in the myocardium implies that sex hormones play a physiological role in cardiac function, myocardial injury and regulation of redox state in the heart. The present study was designed to determine whether castration and androgen replacement results in changes in the capacity of antioxidant defense system in the left ventricle (LV) of adult male rats. To assess this, the activities of antioxidant enzymes (superoxide dismutase [SOD], glutathione peroxidase [GPX], catalase [CAT], and glutathione reductase [GR]), concentrations of non-enzymatic antioxidants (reduced glutathione [GSH], α- and γ-tocopherols) and oxidative stress biomarkers (tissue sulfhydryl groups, protein nitrotyrosine level, and lipid peroxidation) were measured in castrated animals (CAS), castrates replaced with testosterone (CAS+T) and sham-operated controls (Sham). Testosterone was not detectable in serum from gonadectomized rats. The results indicate that castration significantly and negatively affected the antioxidant status of the rat LV, as evidenced by a significant decline in activities of all antioxidant enzymes, a tendency toward lower levels of GSH and protein thiol groups, enhanced lipid peroxidation and higher nitrotyrosine concentrations in left ventricular tissue. Increases in LV tissue concentrations of α- and γ-tocopherols seem to be a compensatory response to enhanced oxidative stress induced by gonadectomy. Re-establishment of physiological serum testosterone level by androgen replacement resulted in a tendency toward a further decrease in the antioxidant defense status in the LV tissue.