| Grant number: | 13/26032-6 |
| Support Opportunities: | Scholarships in Brazil - Scientific Initiation |
| Start date: | March 01, 2014 |
| End date: | February 28, 2015 |
| Field of knowledge: | Biological Sciences - Morphology - Histology |
| Principal Investigator: | Rejane Maira Góes |
| Grantee: | Guilherme Henrique Tamarindo |
| Host Institution: | Instituto de Biociências, Letras e Ciências Exatas (IBILCE). Universidade Estadual Paulista (UNESP). Campus de São José do Rio Preto. São José do Rio Preto , SP, Brazil |
Abstract Prostate is a organ very susceptible to changes during senescence. Benign prostate hyperplasia (BPH) and adenocarcinoma incidence increase dramatically at middle-age. Clinical and experimental studies indicate that prostate pathology is induced by factors as imbalance in estrogen/testosterone ratio, insulin resistance and impairment of antioxidant defense. Obesity and high lipid intake are also considered a risk factor to prostate cancer development. Melatonin is a hormone with multiple functions, including antioxidant activity. In vitro studies corroborate antiproliferative action of melatonin in prostatic cancer cells, but investigations in vivo about its role in gland are scarce. The aim of this study is to investigate if melatonin treatment influences tissue alterations and oxidative stress in prostate of normal or obese middle-age rats. Analyses of tissues alterations will be based on (1) prostatic histology exam, (2) proliferative activity, (3) AR-positive cells number and (4) incidence of pathologic lesions in prostate gland. Biochemistry oxidative stress analyses will be determined by (5) antioxidant enzymes activity and (6) lipidic peroxidation levels. Male Wistar rats at 62th week old will be randomly distributed into groups (n=10 per group), consisted of control (C), control treated with melatonin (CM), obese (Ob), and obese treated with melatonin (ObM). Obesity will be induced at 24th weeks old, by standardized model based on hiperlipidic diet intake (20% lipids). Melatonin (100µg/kg body weight/day) will be provided in drinking water containing 0,01% ethanol, from 48th week to the end of experiment (62th week of old). Testosterone, estrogen and leptin levels will be evaluated by ELISA method. Retroperitoneal fat weight will be quantified at euthanasia. Ventral prostate will be removed and processed for general histologic exam, stereological analyses through point count methodology, immunocytochemistry and histopathologic analyzes. Androgen receptor (AR) and cell proliferation (PCNA) estimate will be performed by immunocytochemistry, quantified and expressed in percentage. Incidence and multiplicity of pathologic lesions will be evaluated, as hyperplasia, stromal and acinar inflammation, intra-epithelial neoplasia and adenocarcinoma. Immunocytochemistry for Bcl-2 may be used in this last case to prove malignancy. Biochemistries specific assays will be made to assess enzymatic activity of following oxidant enzymes - catalase, glutationa S-transferase, glutationa peroxidase and superoxide dismutase. Acquired results will surely collaborate to elucidation of simultaneous effects of obesity and senescence on prostate and cell mechanisms involved. The experiment will provide information about the behavior of prostatic antioxidant system in obesity and aging conditions and reveal information about possible role of exogenous melatonin on prostatic homeostasis under these conditions. | |
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