Pathological lesions incidence and global DNA-methylation in rat prostate under streptozotocin-induced diabetes and melatonin treatment

Chronic hyperglycemia leads to higher production of reactive oxygen species which favors carcinogenesis. The association between diabetes mellitus type 1 (DM1) and prostate cancer is controversial. Melatonin has antioxidant, anti-inflammatory and antiproliferative properties. We aimed to analyze if diabetes induced by streptozotocin favors pathological lesions in rat ventral prostate. It was also examined if melatonin administration at low dosage prevents tissue alterations caused by diabetes and alters the prostate histology of healthy rats. Melatonin was provided in drinking water (10 µg/kg/day) from the 5th week of age until the end of experiment. Diabetes was induced at the 13th week by STZ (40mg/kg, ip). The euthanasia occurred at the 14th week (short-term) and 21st week of age (long-term). Stereological and morphometric analysis of prostate components,as well as the incidence and density of malignant and pre-malignant lesions were assessed. Immunohistochemistry reactions for α-actin, cell proliferation (PCNA), Bcl-2, glutathione S-transferase (GSTpi) and DNA methylation (5-methylcytidine) were performed. Melatonin did not elicited conspicuous changes in healthy animals. Diabetic animals presented higher incidence of atrophy (93%), microinvasive carcinoma (6%), proliferative inflammatory atrophy, PIA (13%), prostatitis (26%) and prostate intraepithelial neoplasia, PIN (20%) associated with an increase of 40% in global DNA methylation. Melatonin attenuated epithelial and smooth muscle cells atrophy, normalized the interacinar collagen organization specially at short-term diabetes and the incidence of PIN (11%), inflammatory cells infiltrates, prostatitis (0%) and PIA (0%) at chonic diabetes. However, these animals also presented microinvasive carcinoma. MLT even at low dosage was able to prevent pre-malignant lesions and normalize epithelium and smc cells atrophy. CEUA: 51/2011