The influence of hyperglycemia and oxidative stress in proliferation and cell death kinetics in prostate acinar epithelium of diabetic rats

Author(s)

Marina Guimarães Gobbo

• Document type: Master's Dissertation
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia
• Defense date: 2011-02-17

Examining board members

Rejane Maira Góes; Mary Anne Heidi Dolder; Luis Antonio Justulin Junior

• Advisor: Rejane Maira Góes

Abstract

The diabetes damages in prostate morphophysiology are well known and are triggered by insulin lack, low androgen levels and hyperglycemia. Previous researches showed an individual variation in morphological prostate response against this disease. In order to clarify the factors responsible for this variation, we examined the correlation between histological response of the prostate with glycemia, serum testosterone and estrogen levels under short term diabetes. It is known that high glucose levels lead to the formation of end products of non-enzymatic glycation (AGE) and the subsequent overproduction of reactive oxygen species. An apoptosis increase was also reported in prostatic epithelium after long periods of diabetes and androgen drift, suggesting the influence of hyperglycemia and oxidative stress in this imbalance. The first experiment was performed to evaluate the impact of estreptozotocin-induced diabetes in the antioxidant system (AOS) of rat ventral prostate (VP) and the influence of supplementation with vitamin C (ascorbic acid). The effects of oxidative stress in androgen sensitivity and proliferation and cell death kinetics, in this gland, were also assessed. For this purpose, diabetes was induced in adult male rats by streptozotocin (4 mg/100g b.w) followed or not by treatment with vitamin C (150 mg/kg b.w./day), by gavage. The following groups were formed: control (C), control treated with vitamin C (C+V), diabetic (D) and diabetic treated with vitamin C (D+V). The animals were sacrificed after 30 days of diabetes onset and the VP was processed. The malondialdehyde levels (MDA) and catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione S-transferase (GST) activities were measured in the prostate and blood. Vitamin C reduced the high apoptosis levels due to diabetes, but did not normalize cell proliferation and it was not totally efficient against oxidative damage. The blood AOS was unaffected by one month of diabetes, but the CAT and GST activities were increased in the gland. The MDA levels and N?-(carboxymetil) lysine (CML) expression, one of the main AGE, were marginally increased in diabetic groups. A second experiment of diabetes induction was based in alloxana induction (42 mg/kg b.w.) with or without insulin treatment. Morphological changes in the VP were examined in histological hystoresin sections, according to different ranges of glycemia. Glucose levels and testosterone/estrogen ratio were inversely related to the VP weight. The atrophy in the distal ends of prostate ducts was associated with high blood glucose levels. Insulin does not prevent the changes caused by diabetes, especially if glycemic control is not effective. These results suggest that oxidative damage is partly responsible for the imbalance in proliferation and cell death caused by diabetes. GST is a good indicator of prostate antioxidant defense in the early stages of this metabolic disturbance and its increased activity may be related to the malignant lesions establishment. Our data indicates that prolonged hyperglycemia combined with hormonal disequilibrium are the main responsible for the drastic changes in the VP of diabetic animals without insulin replacement (AU)

• FAPESP's process: 09/06885-9 - Influence of hyperglicemia and oxidative stress in kinetics of cell proliferation and death of acinar epithelium in the diabetic rat prostate.
• Grantee: Marina Guimarães Gobbo
• Support Opportunities: Scholarships in Brazil - Master