BERKELEY, CA (UroToday.com) - Benign prostatic hyperplasia (BPH) is a common cause of bothersome lower urinary tract symptoms in man, representing a growing nosological entity in terms of health care costs and morbidity. Approximately 50% of men aged between 50 and 60 years, 60% of men aged between 60 and 70 years, and up to 90% of men aged >80 years have some degree of benign prostatic enlargement (BPE). The aetiology of BPH is still far from being fully understood, but multiple partially overlapping and complementary theories have been proposed.
There is some evidence that prostatic inflammation could be a key component in BPE and BPH progression. Numerous of the major key players in chronic inflammation have been studied in BPH: varieties of growth factors and cytokines have been shown to be involved both in the inflammatory process and in the epithelial/stromal prostatic cells interactions. These mediators are released in the prostatic gland by inflammatory cells that can be found on most of the surgery-derived BPH specimens.
The inflammatory cells may trigger a sophisticated and well-orchestrated inflammatory cascade, resulting in excessive oxidative stress, activation of the transcription factor nuclear factor-kappa B (NF-κB), production of several cytokines and overexpression of inducible-cyclooxygenase (COX-2), inducible-nitric-oxide-synthase (iNOS), and 5-lipoxygenase (5-LOX), leading, in turn, to the release of prostaglandins, nitrates, and leukotrienes.
Serenoa repens (SeR), derived from the berries of the saw palmetto tree, is the most popular naturally derived medication for BPH. Several mechanisms of action have been proposed to explain its therapeutic efficacy, including inhibition of 5α-reductase and dihydrotestosterone binding to androgen receptors, a weak α1-adrenergic receptor antagonism, inhibition of growth factors–induced prostate cell proliferation, and inhibition of COX-2 and 5-LOX.
In our study, we aimed to evaluate the efficacy of Profluss® ( SeR-Se-LY) in reducing chronic inflammation in patients with benign prostatic hyperplasia and/or PIN/ASAP. The “Flogosis And Profluss in Prostatic and Genital Disease” (FLOG) study was a multicentre study involving 9 Italian urological centres between January 2009 and December 2010, analyzing prospectively collected data of two category of patients affected by BPH and/or PIN/ASAP. Almost all surgery-derived BPH specimens show inflammatory infiltrates at histological examination; yet most of these patients neither have clinical signs of infection nor any correlation with bacterial or other foreign antigens.
In a study by Robert et al. it was found that most patients, treated by surgery for complicated and/or symptomatic BPH, had inflammatory cells infiltrating BPH tissues: 81% had T-lymphocytes markers, 52% had B-lymphocytes markers, and 82% had macrophages markers. Therefore, patients with high-grade prostatic inflammation IPSS score and prostate volume were significantly higher.
Among all phytotherapics, the lipidosterolic extract of Serenoa repens, a compound used to relief symptoms of BPH, had shown an anti-inflammatory activity modifying the production of leukotrienes and 5 hydroxyeicosatetraenoic acid, via the inhibition of the oxidative enzyme 5 lypoxygenase rather than phospholipase A2 or cell viability. Since the infiltration of inflammatory cells appears to have a role in BPH, inhibition of the production of chemotactic leukotrienes and other 5 lypoxygenase metabolites by Serenoa repens could be useful in BPH treatment.
Serenoa repens, in a multicenter, open, pilot study, was also evaluated for its effects on inflammatory markers. Tumor necrosis factor–α and IL-1b were dramatically lower in the Serenoa repens-treated group; both biological markers have been used as indicators of prostatic inflammation in cases of chronic prostatitis. It has been hypothesized that SeR, Ly, and Se, administered together, might amplify their therapeutic efficacy on the proliferative and inflammatory component of BPH. Analyzing specimens from patients with PIN high grade and/or ASAP, a statistical significant reduction in the extension, and in the grading of the inflammatory cells infiltrate was demonstrated in the patients treated with SeR+Ly+Se (Group I) while among patients with BPH (Group II), total interstitial mononuclear cells, B lymphocytes, T lymphocites and macrophages were significantly reduced at 3-month evaluation compared with control group.
Therefore it was confirmed by immune-histochemical technique using monoclonal antibodies, that mononuclear cell infiltration (B-lymphocytes CD20, T-lymphocytes CD3-CD8 and macrophages CD68) is the most common pattern. SeR+Ly+Se combination therapy resulted in a statistically significant reduction of this inflammatory infiltrate.
We demonstrated the anti-inflammatory activity of the combination of SeR+Se+LY in patients with histological inflammation detected on biopsy specimens. Based on these findings, patients with bladder outlet obstruction may benefit from this therapy on the inflammatory component of BPH.
Written by:
Giorgio Ivan Russo, MD and Giuseppe Morgia, MD as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.
Department of Urology, University of Catania, Catania, Via Santa Sofia 78, 95100, Italy
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