OBJECTIVETo establish a rat model of autoimmune prostatitis using purified prostatic proteins (PPP).

METHODSThirty-six male Wistar rats were randomized into three groups of equal number to receive intramuscular injection of normal saline (normal control group) and PPP at 15 mg/ml (low-concentration group) and 80 mg/ml (high-concentration group). At 4 weeks after modeling, the rats were sacrificed for HE staining of the prostate tissue and examination of the inflammatory factors IL-8 and IL-10 in the serum, immunoglobulins IgA and IgM, and regulatory T cells Th1/Th2.

RESULTSThree rats died in the high-concentration PPP group but none in the low-concentration PPP and normal control groups. Gross observation of the prostate showed increased volume and hard texture of the prostate in the two PPP groups, but no significant change in the normal controls. Pathological examination exhibited morphological damage to the prostatic tissue and inflammatory cellular infiltration in the experimental rats. The serum level of IL-8 was significantly higher in the low- and high-concentration PPP groups ([129.07 +/- 11.48] and [147.58 +/- 17.70] pg/ml) than in the control ([94.12 +/- 7.04] pg/ml) (P < 0.05), while that of IL-10 was remarkably lower in the former two groups ([227.14 +/- 18.19] and [187.14 +/- 16.32] pg/ml) than in the latter ([252.48 +/- 21.72] pg/ml, P < 0.05). The serum level of IgA was markedly elevated in the low- and high-concentration PPP groups as compared with that in the control ([0.25 +/- 0.37] and [0.31 +/- 0.42] vs [0.19 +/- 0.14] mg/ml, P < 0.05), and so was that of IgM ([0.23 +/- 0.41] and [0.34 +/- 0.58 ] vs [0.17 +/- 0.33] mg/ml, P < 0.05). No significant changes were observed in the levels of regulatory T cells Th1/Th2.

CONCLUSIONBoth low and high concentrations of purified prostatic proteins can be used for the construction of autoimmune prostatitis models in rats, while low concentration is preferable for its advantages of lower mortality of the rats and inducement of more consistent manifestations of autoimmune prostatitis.

Animals ; Autoimmune Diseases ; blood ; chemically induced ; pathology ; Disease Models, Animal ; Humans ; Interleukin-10 ; blood ; Interleukin-8 ; blood ; Male ; Prostatic Secretory Proteins ; administration & dosage ; pharmacology ; Prostatitis ; blood ; chemically induced ; pathology ; Rats ; Rats, Wistar

Inflammation of the prostate can be induced experimentally in rats by the subcutaneous administration of estrogen. However, it is usually achieved at the price of some alteration in the sex steroid hormone balance and morphological changes in the prostate. In this study, a soy-extracted isoflavone mixture with weak estrogenic activity was administered orally in an attempt to induce prostatitis in a more physiologic way and to characterize the inflammation induced. A total of 36 male Sprague-Dawley rats, 8 weeks old, were divided into 2 groups. The control group was fed with only an AIN-76A diet containing no detectable phytoestrogen and the experimental group was fed with AIN-76A and a soy- extracted isoflavone mixture (genistein 60.0% and daidzein 19.6%), 300mg/kg body weight for 9 weeks. The sequential body weight and prostate weight at necropsy were measured. A histologic examination and histomorphometry assessed the changes in the prostate. The serum concentrations of testosterone and dihydrotestosterone were measured to estimate the effects on the androgen level. Intraprostatic concentrations of genistein and daidzein were measured by gas chromatography/ mass spectroscopy (GC/MS). While no sign of prostate inflammation was apparent in the control group, severe inflammatory changes in the stroma, increased epithelial detachment and inflammatory exudates within the glandular lumen of the dorsolateral prostate were observed in more than 80%(15/18) of the experimental group. However, there was no significant difference in the ventral prostate between the two groups. The daidzein and genistein concentrations in both the lateral and ventral prostates were significantly higher in the experimental group than in the control group where no isoflavone was detectable. In addition, the concentrations were much higher in the dorsolateral than in the ventral prostate. Although the body weight gain was not consistent in the experimental group, there were no significant differences in the prostate weight and serum androgen level between groups. In summary, when a soy-extracted genistein and daidzein-rich isoflavone mixture was administered orally into rats, prostatic inflammation with characteristic lobe specificity developed. The present method of inducing prostatitis seems to be a more physiologic than an estrogen-induced experimental model, and sequential pharmacokinetic studies might help in establishing this model as a more valuable tool in assisting future research in this field.
Administration, Oral ; Androgens/blood ; Animal ; Body Weight/drug effects ; Isoflavones/metabolism/*toxicity ; Male ; Organ Weight/drug effects ; Prostatitis/*chemically induced/pathology ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo evaluate the therapeutic effect of Compound Xuanju Capsule (CXC) on autoimmune prostatitis in rat models.

METHODSSixty healthy male Wistar rats were randomly divided into five groups of equal number: blank control, low-concentration purified prostate protein (low-conc PPP), low-conc PPP + CXC treatment, high-concentration PPP (hi-con PPP), and hi-conc PPP + CXC treatment. Autoimmune prostatitis models were established by intragastric administration of PPP solution at 15 mg/ml (low concentration) and 80 mg/ml, respectively. At 30 days after modeling, the rats in the blank control and low-conc and hi-conc PPP model groups were treated with normal saline, and those in the other two groups with CXC at a daily dose of 0.068 g/ml. At 30, 45, and 60 days, all the animals were sacrificed for observation of pathological changes in the prostate tissue and determination of the levels of IL-8, IL-10, and TNF-alpha in the serum.

RESULTSCompared with the PPP models, the hi-conc PPP + CXC group showed significantly reduced levels of IL-8 and TNF-alpha in the serum at 45 days ([148.54 +/- 17.23] and [62.14 +/- 5.59] pg/ml vs [100.77 +/- 11.08] and [32.63 +/- 2.91] pg/ml, P < 0.05) and at 60 days ([143.69 +/- 17.28] and [59.38 +/- 5.50] pg/mlvs [95.77 +/-10.53] and [29.63 +/- 2.66] pg/ml, P < 0.05), and so did the low-cone PPP + CXC group at 45 days ([128.47 +/- 12.21] and [40.43 +/- 3.64] pg/ml vs [111.76 +/- 10.07] and [35.44 +/- 3.17] pg/ml, P < 0.05) and at 60 days ([131.07 +/- 10.93] and [43.34 +/- 3.91] pg/ml vs [97.46 +/- 8.75] and [30.44 +/- 2.75] pg/ml, P < 0.05). The serum level of IL-10 was remarkably elevated in the hi-cone PPP + CXC group as compared with that of the PPP models at 45 and 60 days ([189.14 +/- 16.78] and [184.14 +/- 15.89] pg/ml vs [230.48 +/- 29.96] and [248.48 +/- 31.03] pg/ml, P < 0.05), and so was it in low-cone PPP + CXC group ([223.14 +/- 17.87] and [224.14 +/- 17.93] pg/ml vs [231.42 +/- 23.18] and [249.42 +/- 24.97] pg/ml, P < 0.05). Pathological examination revealed morphological damages to the prostate tissue and infiltration of inflammatory cells in the model rats, but no obvious changes in the normal controls. At 15 days of treatment, the rats in the PPP + CXC group showed enlarged prostate glandular cavity, mild proliferation of epithelial cells, no obvious infiltration of inflammatory cells in the interstitial tissue, and a few visible fibrous tissues under the light microscope.

CONCLUSIONCompound Xuanju Capsule is efficacious on autoimmune prostatis in rats by reducing inflammatory changes in the prostate tissue and improving the expression of inflammatory factors.

Animals ; Autoimmune Diseases ; blood ; chemically induced ; drug therapy ; Capsules ; Interleukin-10 ; blood ; Interleukin-8 ; blood ; Male ; Prostatic Hyperplasia ; pathology ; Prostatic Secretory Proteins ; Prostatitis ; blood ; chemically induced ; drug therapy ; Random Allocation ; Rats ; Rats, Wistar ; Tumor Necrosis Factor-alpha ; blood

PURPOSE: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS, NIH category III) accounts for 90-95% of prostatitis cases. However, standard treatment has not yet been established. It is known that polyphenols have an inhibitory effect on inflammation by their antioxidative capacity, and oligonol, a polyphenol derivative, has much higher bioavailability and bioactivity than common polyphenols. We investigated the anti-inflammatory effects and mechanisms of oligonol in estradiol-induced prostatitis rat models. MATERIALS AND METHODS: Prostatitis was induced by 17 beta-estradiol (E2) and dihydrotestosterone (DHT) in Wistar male rats (n = 20). Ten rats were placed in the oligonol-treated group and 10 in the E2 + DHT-treated group. The other 10 rats were also included as normal control group. Oligonol (60 mg/kg/day) was administered via gavage tube for 4 weeks. Superoxide dismutase (SOD), glutathione peroxidase (GPx), and tumor necrosis factor-alpha (TNF-alpha) were quantified, and phosphorylation of IkappaBa and histological changes were also evaluated in prostatic tissue. RESULTS: The SOD and GPx activity showed tendencies to increase in the oligonol-treated group compared to the normal control group. TNF-alpha expression was slightly reduced in the oligonol-treated group. Western blotting demonstrated that phosphorylation of IkappaBa in the oligonol-treated group was significantly lower than in the normal control group. The E2 + DHT-treated group revealed severe atrophy of acinar epithelial cells and infiltration of leukocytes and lymphocytes in the prostate, however, the oligonol-treated group showed overall reduction in inflammatory features. CONCLUSION: This study demonstrates that oligonol improves estradiol-induced non-bacterial prostatitis by regulating phosphorylation of IkappaBa. These findings suggest that oligonol has a beneficial effect on prevention and treatment of CP/CPPS.
Animals ; Blotting, Western ; Body Weight/drug effects ; Estradiol/*adverse effects ; Flavonoids/*therapeutic use ; Immunoassay ; Male ; Phenols/*therapeutic use ; Prostate/drug effects/pathology ; Prostatitis/*chemically induced/metabolism/*prevention & control ; Rats ; Rats, Wistar ; Superoxide Dismutase/metabolism ; Tumor Necrosis Factor-alpha/metabolism