Article

Chronic bacterial infection and inflammation incite reactive hyperplasia in a mouse model of chronic prostatitis

Department of Surgery, Division of Urology, University of Wisconsin School of Medicine and Public Health, 600, Highland Ave, Madison, WI 53792, USA.
The Prostate (Impact Factor: 3.57). 01/2007; 67(1):14-21. DOI: 10.1002/pros.20445
Source: PubMed

ABSTRACT Chronic inflammation is postulated to contribute to prostate carcinogenesis. We developed a mouse model of chronic prostatitis to test whether infection-induced chronic inflammation would incite reactive changes in prostatic epithelium.
Prostate tissues harvested from either phosphate-buffered saline (PBS) or E. coli-infected mice were evaluated for histological changes and immunostained for markers of oxidative stress and epithelial cell proliferation.
As compared to PBS-treated controls, mice infected with E. coli bacteria for 5 days showed foci of uniformly acute inflammation in the glandular lumen and a persistent inflammation at 12 weeks post-inoculation in the stroma. Prostatic glands showing varying degrees of atypical hyperplasia and dysplasia had stronger staining for oxidative DNA damage and increased epithelial cell proliferation than normal prostatic glands.
These data demonstrate that chronic inflammation induces reactive hyperplasia associated with oxidative stress injury and support the proposed linkage among inflammation, oxidative DNA damage, and prostate carcinogenesis.

0 Followers
 · 
87 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: To investigate the urothelial changes in the pathogenesis of ureteropelvic junction obstruction (UPJ-O).
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND: Benign prostatic hyperplasia (BPH) affects many men after the age of 50 years. Inflammation and oxidative stress along with apoptotic changes are thought to play an important role in the pathology of BPH. Pomegranate contains a variety of polyphenolic compounds that have been studied in a medley of diseases for their anti-oxidant, anti-inflammatory and pro-apoptotic properties. Therefore, this study examined the effect of Pomegranate Fruit Extract (PFE) on the development of BPH using a testosterone-induced BPH model in rats. METHODS: A total of 48 rats were randomly divided into six groups of eight, one group served as the control, BPH was induced by testosterone 3 mg/kg S.C. daily in four groups, three of them received PFE by oral gavage daily at doses of 25, 50, and 100 mg/kg respectively, while one group received PFE at a dose of 50 mg/kg without induction of BPH. RESULTS: PFE at a dose of 100 mg/kg was the most effective in decreasing testosterone-induced increase in prostate weight, prostate weight/body weight ratio, and PAP levels by 30.8%, 55%, and 68% respectively and in preventing the accompanying histological changes. In the BPH model, testosterone significantly decreased GSH, SOD, and CAT to 0.45, 0.64, and 0.88 of the control group values respectively, and significantly increased MDA by >6-fold. In combination with testosterone, PFE dosed at 100 mg/kg significantly increased GSH, SOD, and CAT to 0.83, 0.92, and 0.93 of the control group values respectively, whereas MDA was significantly decreased by 72% compared with the testosterone treated group. In addition to this, at the range of doses studied, PFE lowered COX-II, iNOS, Ki-67 expression, and increased apoptotic index. CONCLUSION: The current findings elucidate the effectiveness of PFE in preventing testosterone-induced BPH in rats. This could be attributed, at least partly, to its anti-oxidant, anti-inflammatory, and pro-apoptotic properties.
    The Prostate 02/2015; DOI:10.1002/pros.22951 · 3.57 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Lower urinary tract symptoms (LUTS) including urinary frequency and nocturia are common in aging men. Recent studies have revealed a strong association of prostatic inflammation with LUTS. We developed an animal model of bacterial induced, isolated prostatic inflammation and examined the effect of prostatic inflammation on voiding behavior in adult C57BL/6J mice. Prostatic inflammation was induced by transurethral inoculation of uropathogenic E. coli-1677. Bacterial cystitis was prevented by continuous administration of nitrofurantoin. Hematoxylin and eosin (H&E) staining and bacterial culture were preformed to validate our animal model. Voiding behavior was examined by metabolic cage testing on post-instillation day 1 (PID 1), PID 4, PID 7 and PID 14 and both voiding frequency and volume per void were determined. Mice with prostatic inflammation showed significantly increased voiding frequency at PID 1, 7 and 14, and decreased volume per void at all time points, as compared to mice instilled with saline and receiving nitrofurantoin (NTF). Linked analysis of voiding frequency and voided volumes revealed an overwhelming preponderance of high frequency, low volume voiding in mice with prostatic inflammation. These observations suggest that prostatic inflammation may be causal for symptoms of urinary frequency and nocturia.
    PLoS ONE 02/2015; 10(2):e0116827. DOI:10.1371/journal.pone.0116827 · 3.53 Impact Factor