Differential tempol effects in prostatic cancer: angiogenesis and short- and long-term treatments.

Prostate cancer (PCa) is the second cause of cancer death among men worldwide. Several processes are involved in the development and progression of PCa such as angiogenesis, inflammation and oxidative stress. The present study investigated the effect of short- or long-term Tempol treatment at different stages of prostate adenocarcinoma progression, focusing on angiogenic, proliferative, and stromal remodeling processes in TRAMP mice. The dorsolateral lobe of the prostate of TRAMP mice were evaluated at two different stages of PCa progression; early and late stages. Early stage was again divided into, short- or long-term. 50 mg/kg Tempol dose was administered orally. The results demonstrated that Tempol mitigated the prostate histopathological lesion progressions in the TRAMP mice in all treated groups. However, Tempol increased molecules involved in the angiogenic process such as CD31 and VEGFR2 relative frequencies, particularly in long-term treatment. In addition, Tempol upregulated molecule levels involved in angiogenesis and stromal remodeling process VEGF, TGF-ß1, VE-cadherin and vimentin, particularly, in T8-16 group. Thus, it was concluded that Tempol treatment delayed prostatic lesion progression in the dorsolateral lobe of the TRAMP mice. However, Tempol also led to pro-angiogenic effects and glandular stromal microenvironment imbalance, especially, in the long-term treatment.

Jaboticaba peel powder and jaboticaba peel aqueous extract reduces obesity, insulin resistance and hepatic fat accumulation in rats.

This study investigated the effects of freeze-dried jaboticaba peel (FJP) and jaboticaba tea (JE) on obesity parameters of diet-induced obese rats. Thirty-six male Wistar rats were distributed into six groups: AIN-93 M feed a normal control diet; HFF (obese control) feed a high-fat and fructose diet; Prevention FJP (P. FJP) and Treatment FJP (T. FJP) feed HFF diet with 2% of FJP powder, for 12 and 6 weeks respectively; Prevention JE (P. JE) and Treatment JE (T. JE) were feed with HFF diet and the water was substituted by JE, for 12 and 6 weeks, respectively. Lipid profile, glucose, adiponectin and leptin were measured. Glucose and insulin tolerance, also pancreatic islet insulin secretion were determined. Liver morphology and fat liver accumulation were evaluated. Results showed that HFF-diet induced weight gain, dyslipidemia, glucose intolerance, insulin resistance and hepatic steatosis. All FJP and JE treatments reduced weight gain, adiposity and improved insulin sensitivity. Twelve weeks supplementation increased HDL-cholesterol and prevented hepatic steatosis. Our results suggest that FJP and JE act as functional foods, being a dietary strategy to prevent or control obesity. FJP and JE 12 weeks supplementation can modulate important parameters of obesity and insulin metabolism, preventing liver steatosis in obese rats.

Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) model: A good alternative to study PCa progression and chemoprevention approaches.

The use of genetically modified animals has been studied in scientific research over time as a way to discover new treatments or even a cure for various diseases. Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) is a model for prostate cancer (PCa) that develops lesions that range from preneoplastic to metastasis. Its similarity to human PCa brings essential knowledge about disease development as well as making possible to investigate different degrees of the tumor profile. We reviewed the literature regarding five important areas relating to PCa progression in the TRAMP model. We also present some useful PCa models comparing them to TRAMP. Furthermore, we investigated the effect of some therapies related to these areas highlighting the best approaches that can delay PCa progression. The revised studies showed that TRAMP cancer stages are well established from 8 to 30 weeks of age, which makes possible to interfere in specific times of PCa development. Moreover, inflammatory and angiogenic blockage before the appearance of malignant lesions retarded PCa progression and showed better results than therapeutical approaches in other phases in TRAMP mice. Reactive stroma is less studied than other areas, although it has been showing a particular relevance in PCa as a milestone in malignant transformation through the modulation of TGF-ß, vimentin, and αSMA. We concluded that even years after its creation, the TRAMP model is still one of the most essential tools for PCa study, as well as for the development of new strategies to prevent the disease.

Morphological and morphometrical changes on adult Wistar rat testis caused by chronic sodium arsenite exposure.

Arsenic is a contaminant that occurs naturally in the environment, and it is related to several diseases, such as cancer and severe metabolic diseases. Sodium arsenite effects on testes rats are not fully understood regarding morphology and stereology; thus, it becomes necessary to evaluate possible changes in these parameters under low concentrations and simulating occupational exposure. Therefore, the aim of this study was to analyze the morphometrical and stereological changes on rat testis treated with sodium arsenite. The treatment was accomplished using 5 mg/kg of sodium arsenite by gastric gavage in Wistar rats, which experiment lasted 8 weeks. Organs were weighed and gonadosomatic index (GSI) was calculated. Using the software Image Pro Plus, seminiferous tubule diameter was measured, and the volume densities of testicular parenchymal components were obtained. It was counted 200 hundred spermatozoa and classified as normal or abnormal. The parameters means of control (N = 5) and treated (N = 7) groups were compared by U Mann-Whitney's test, and the results were considered significant for P < 0.05. We observed a decrease in seminiferous tubule diameter, as well as testis weight. These finds may be related with disorders of testosterone metabolism due to activation of immunological responses of macrophage, which inhibit the steroidogenesis. Thus, we conclude that sodium arsenic does not impair the animal's general health, but its exposure induces biochemical and tissue changes.

Arsenic trioxide exposure impairs testicular morphology in adult male mice and consequent fetus viability.

The acute promyelocytic leukemia (APL) is a rare disease, affecting 0.1/100,000 individuals globally. Despite significant advances in APL therapy, some patients still experience relapsed disease. Currently, arsenic trioxide (As2O3) was found to be effective in relapsed APL treatment and considered as standard treatment for these cases. However, it has been shown that exposure to As2O3 may exert adverse effects on the male reproductive system since this substance might also induce apoptosis of other important cell types including stem cells. Studies demonstrated that treatment with this metallic substance decreased plasma levels of testosterone and interfered with sperm parameters such as concentration, motility, and viability. In addition, As2O3 was found to produce significant damage to spermatocytes, which may be associated with testicular toxicity and consequent inhibition of spermatogenesis. The aim of this study was to determine sub-chronic treatment effects of As2O3 on sperm and testicular morphology, androgen receptor (AR) immunoreactivity in testes and epididymis, in addition to evaluation of fertility parameters in adult male mice. Thirty adult Swiss mice were divided into three experimental groups: control; received distilled water (vehicle) while treated received 0.3 or 3 mg/kg/day As2O3 subcutaneously, for 5 days per week, followed by 2 days of interruption, for 5 weeks. Results showed that As2O3 (1) decreased spermatozoa number, (2) produced seminiferous epithelium degeneration and exfoliation of germ cells tubule lumen (3) altered nucleus/cytoplasm proportion of Leydig cells and (4) reduced AR immunoreactivity in both Leydig and epithelial epididymal cells. Further, fetal viability tests demonstrated an increase in post-implantation loss in females that were mated with As2O3-treated males. Data indicate that As2O3 exposure altered the spermatogenic process and subsequently fetal viability.