This study investigated the antioxidant system response of male reproductive organs during early and late phases of diabetes and the influence of melatonin treatment. Melatonin was administered to five-week-old Wistar rats throughout the experiment, in drinking water (10 μg/kg b.w). Diabetes was induced at 13 weeks of age by streptozotocin (4.5 mg/100 g b.w., i.p.) and animals were euthanized with 14 or 21 weeks old. Activities of catalase (CAT), glutathione-S-transferase (GST), glutathione peroxidase (GPx), and lipid peroxidation were evaluated in prostate, testis, and epididymis. The enzymes activities and lipid peroxidation were not affected in testis and epididymis after one or eight weeks of diabetes. Prostate exhibited a 3-fold increase in GPx activity at short-term diabetes and at long-term diabetes there were 2- and 3-fold increase in CAT and GST, respectively (p ≤ 0.01). Melatonin treatment to healthy rats caused a 47% increase in epididymal GPx activity in 14-week-old rats. In prostate, melatonin administration normalized GST activity at both ages and mitigated GPx at short-term and CAT at long-term diabetes. The testis and epididymis were less affected by diabetes than prostate. Furthermore, melatonin normalized the enzymatic disorders in prostate demonstrating its effective antioxidant role, even at low dosages.

Recent studies have shown a positive association of cancer and obesity, but the morphological and molecular mechanisms involved in this relationship are still unknown. This study analysed the impact of long-term obesity on rat prostate, focusing on stromal changes. Male adult Wistar rats were treated with high-fat diet to induce obesity, while the control group received a balanced diet. After 30 weeks of feeding, the ventral prostate was analysed by immunohistochemistry for cell proliferation, smooth muscle α-actin, vimentin, chondroitin sulphate and metalloproteinases (MMP-2 and 9). The content of androgen receptor (AR), oestrogen receptors (ERs) and vascular endothelial growth factor (VEGF) was measured by Western blotting, and activity of catalase and Glutathione-S-Transferase (GST) were quantified by enzymatic assay. Long-term obesity decreased testosterone plasma levels by 70% and resulted in stromal prostate hyperplasia, as evidenced by increased collagen fibres. Such stromal hyperplasia was associated with increased number of blood vessels and raised VEGF content, and increased expression of chondroitin sulphate, vimentin, α-actin and MMP-9. In spite of the high cell density in prostate, the proliferative activity was lower in the prostates of obese rats, indicating that hyperplasia was established during the early phases in this obesity model. AR levels increased significantly, whereas the ERα decreased in this group. Moreover, the levels of catalase and GST were changed considerably. These findings indicate that long-term obesity, besides disturbing the antioxidant control, causes intense stromal remodelling and release of factors that create an environment that can promote proliferative disorders in the gland, culminating with diffuse hyperplasia.

SUMMARYMelatonin may be used as an antioxidant in therapy against systemic sequelae caused by oxidative stress in diabetes. However, as melatonin has a major role in regulating reproductive activity, its consequence on reproductive parameters under diabetes needs to be better clarified. We have studied whether prior and concomitant treatment of juvenile Wistar rats with low doses of melatonin interferes in reproductive damage induced by experimental diabetes after 1 and 8 weeks. The consequences of melatonin administration since weaning on reproductive parameters of healthy rats at adulthood were also evaluated. Melatonin was provided in drinking water (10 lg/kg b.w./day) after weaning (5-week-old). Diabetes was induced by streptozotocin injection (4.5 mg/100 g b.w.) at 13-week-old rats, and rats were euthanized 1 and 8 weeks after disease onset. Diabetes decreased circulating testosterone levels (~35% to 1 week;~62% to 2 months; p < 0.01) but did not affect testes sperm counts. Two months of diabetes reduced the sperm reserve and led to atrophy of epididymal cauda. Both 1-week and 2-month diabetes impaired sperm motility, decreased the number of spermatozoa with progressive movement, and increased the number of immotile sperm. Melatonin intake reduced serum testosterone levels~29% in healthy 14-week-old and~23% in 21-week-old rats and reduced daily testicular sperm production~26% in the latter disease stage, but did not interfere in sperm reserves and transit time for both experimental periods. Exogenous melatonin prevented the serum testosterone decrease and damage to sperm motility in diabetic rats and attenuated reduction in sperm counts and transit time induced by 1-week diabetes but did not avoid this decrease at 2-month diabetes. Low doses of melatonin administered prior to and during experimental diabetes attenuated damage to testicular steroidogenic activity and preserved sperm motility, but not sperm reserves in the rat. Our data indicated a differential action of melatonin in normoglycemic and hyperglycemic conditions, particularly in sperm motility and testosterone production by Leydig cells.