Therapeutic effects of ß-caryophyllene on proliferative disorders and inflammation of the gerbil prostate.

BACKGROUND: The prostate is susceptible to changes in androgen levels, which can play an important role in the development of Benign Prostatic Hyperplasia (BPH). Natural compounds have beneficial properties for organisms and can be an important therapeutic strategy in the treatment of diseases. ß-Caryophyllene (BCP) is a phytocannabinoid present in several medicinal and food plants species and has shown beneficial effects in different organs. However, little is known about its effects on the prostate. The present study seeks to evaluate the effects of exposure to BCP on the morphophysiology of the ventral prostate of adult gerbils supplemented with testosterone. METHODS: Animals were distributed into four groups (n = 8/group): Intact control (C); ß-Caryophyllene (BCP): ß-Caryophyllene (50 mg/kg/day); Testosterone (T): animals received subcutaneous injections of Testosterone Cypionate (3 mg/Kg), on alternate days, for one month and were euthanized 30 days supplementation ended; Testosterone and ß-Caryophyllene (TBCP): animals were exposed to testosterone cypionate (3 mg/Kg) to induce hyperplastic alterations followed by daily BCP (50 mg/kg). Morphological, biometric, immunohistochemical, and serological analyses were performed. RESULTS: Proliferative disorders and inflammatory foci were present in the ventral prostate of all experimental groups. An increase in the multiplicity of benign intraepithelial neoplasm and subepithelial inflammatory foci was observed in T group. The incidence of intraluminal inflammatory foci and microinvasive carcinoma was verified only in the T group. Cellular rearrangement and tissue remodeling occurred in the prostate of groups exposed to phytocannabinoids. A reduction was observed in the frequency of PHH3 and Cox2 markers in the prostatic epithelium of TBCP in comparison with T. A decrease in F4/80 and CD163 positive macrophages were also observed in the prostatic stroma of the TBCP group in comparison with T. The results suggest that BCP had favorable effects on BPH, reducing the proliferation and frequency of some inflammatory cells. CONCLUSION: BCP impacts the tissue remodeling process in the premalignant prostate environment and that the use of this phytocannabinoid can have a promising effect in the handling of BPH.

Neonatal exposure to aluminum chloride disrupts branching morphogenesis and hormonal signaling of the ventral male prostate and female prostate of gerbils.

BACKGROUNG: Exposure to environmental pollutants in critical developmental windows may predispose the prostate to permanent changes in its homeostasis. Thus, it is essential to know the effects that environmental toxics, such as aluminum, can cause during the development of this gland. The aim of this study was to evaluate the effects of neonatal aluminum exposure on the ventral male prostate and the female prostate of 15 days old gerbils. METHODS: Male and female gerbils were exposed orally to 10 mg/kg/day of aluminum chloride from the 1st to the 14th postnatal day life. At 15 days of life, gerbils were euthanized and their prostates were collected for biometric, morphological, morphometric, immunohistochemical and three-dimensional reconstruction analyzes. RESULTS: Al exposure caused a reduction in body weight in males and a significant increase in serum testosterone levels in females. Prostate branching morphogenesis was intensified in males, who had greater length, number and area of prostatic epithelial buds. Additionally, Al altered the prostate hormonal regulation of males and females, causing up regulation of the androgen receptor and estrogen receptor alpha in the female prostate, and increased immunostaining of the androgen receptor in the ventral male prostate. These changes were associated with an increased rate of epithelial and stromal cell proliferation in both sexes. CONCLUSION: Together, these results indicate that Al altered the neonatal development of the prostate and that this metal acted as an endocrine disruptor in this gland.

Budding process during the organogenesis of the ventral prostatic lobe in Mongolian gerbil.

The prostate is a mammalian gland that shows a complex process of organogenesis. Here, a morphological study to characterize the organogenesis of the ventral prostate lobe in male gerbils was conducted. The urogenital sinus (UGS) was dissected out and processed for paraffin embedding. Histological sections were subjected to cytochemical, immunofluorescence, immunohistochemical, and three-dimensional reconstruction techniques. We found that the first ventral buds emerged from the ventral urethral epithelium between the days 20 and 21 of prenatal life, reaching the ventral mesenchymal pad and initiating the branching process on the first day of postnatal life. The buds presented a V-shaped elongation, suggesting that the smooth muscle layer (SML) plays an important role during budding events. Indeed, whereas the androgen receptor (AR) was preferentially found in the UGS mesenchyme (UGM), estrogen receptor alpha (ERα) was localized in both the UGM and in the emerging buds. This study characterized the morphological aspects of the budding process in a different rodent from rat and mice, serving as a new model for future studies on developmental biology of the prostate.

A modified method for the selective staining of elastic system fibers in methacrylate tissue sections

The elastic system fibers are abundant elements of the extracellular matrix found in organs such as skin, blood vessels, lung and in elastic cartilage and elastic tendons. These fibers have been studied by several selective staining methods, such as resorcin-fuchsin for light microscopy and hematoxylin-eosin plus fluorescence and confocal scanning laser microscopy. However, most of these techniques are only efficient for tissues embedded in paraffin or paraplast, since most dyes show low penetration into glycol methacrylate resins. In this report, we describe a variation of Weigert´s resorcin-fuchsin method that involves the pretreatment of resin sections with potassium permanganate. This procedure increased the affinity between the dye and elastic fibers, and stained the elastic fibers in black of dark violet, the nuclei in purple and other structures in light blue. Thus, this modification of the original method provided excellent artifact-free demarcation of elastic fibers in well-preserved tissues.