Reactive derivatives of non-enzymatic glucose-protein condensation reactions integrate a heterogeneous group of irreversible adducts called advanced glycation end-products (AGEs). Numerous studies have investigated the role of the AGEs in cardiovascular system; however, its contribution to erectile dysfunction (ED) that is an early manifestation of cardiovascular disease has been less intensively investigated. This review summarizes the most recent advances concerning AGEs effects in the cavernous tissue of the penis and in ED onset, particularly on diabetes and aging, conditions that not only favor AGEs formation, but also increase risk of developing ED. The specific contribution of AGE on intra- and extracellular deposition of insoluble complexes, interference in activity of endothelial nitric oxide (NO) synthase, NO bioavailability, endothelial-dependent vasodilatation, as well as molecular pathways activated by receptor of AGEs are presented. Finally, the interventional actions that prevent AGEs formation, accumulation or activity in the cavernous tissue and that include nutritional pattern modulation, nutraceuticals, exercise, therapeutic strategies (statins, anti-diabetics, inhibitors of phosphodiesterase-5, anti-hypertensive drugs) and inhibitors of AGEs formation and crosslink breakers, are discussed. From this review, we conclude that despite the experiments conducted in animal models pointing to the AGE/RAGE axis as a potential interventional target with respect to ED associated with diabetes and aging, the clinical data have been very disappointing and, until now, did not provide evidence of benefits of treatments directed to AGE inactivation.
Green tea (GT) and its components have been shown to possess antiobesity properties and the corresponding mechanisms of action are being investigated, given the epidemic proportions of obesity incidence. In the current work, we used 12-mo-old male Wistar rats to test the effect of 6 mo of treatment with GT as the sole drinking beverage (52.8 ± 6.4 mL/d) on adipose tissue (AT). AT aromatase expression was determined by Western blotting, plasma concentrations of 17β-estradiol and testosterone were determined by RIA, and adipocyte size determined by measuring diameter in tissue sections. Proliferation and apoptosis were also assessed by Ki67 immunostaining and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling, respectively. Evaluations were made in subcutaneous (sc) AT and visceral (v) AT. Body weight increased over time in both groups (P < 0.001), but the increase was more pronounced in controls (P < 0.001) and food and fluid intake did not influence that effect. At the end of the experiment, aromatase expression increased in the AT (318.5 ± 60.6% of control in scAT, P < 0.05, and 285.5 ± 82.9% of control in vAT, P < 0.01). AT of GT-treated rats had a higher percentage of proliferating cells (204.1 ± 19.5% of control in scAT, P < 0.01, and 246.6 ± 50.2% of control in vAT, P < 0.01) and smaller adipocytes (78.3 ± 1.7% of control in scAT, P < 0.001, and 87.9 ± 3.2% of control in vAT, P < 0.05). GT also increased the number of apoptotic cells in vAT (320.4 ± 21.9% of control; P < 0.001). These results suggest new mechanisms for GT on body weight and highlight its potential benefit to prevent or treat obesity and the metabolic syndrome.