Yonsei Med J.  2009 Jun;50(3):391-398. 10.3349/ymj.2009.50.3.391.

Preventive Effects of Oligomerized Polyphenol on Estradiol-Induced Prostatitis in Rats

• Kim DS
• Lee EJ
• Cho KS
• Yoon SJ
• Lee YH
• Hong SJ

• KMID: 1758568
• DOI: http://doi.org/10.3349/ymj.2009.50.3.391

Abstract

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.

Keyword

Nonbacterial prostatitis; inflammation; polyphenol; oligonol; oxidative stress

MeSH Terms

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

Figure

• 

  Fig. 1 Experimental schedule. DHT, dihydrotestosterone.

• 

  Fig. 2 Effect of E2 +DHT and oligonol on body weight and prostate weight. (A) The E2 + DHT and oligonol-treated group showed significantly reduced body weight compared to the normal control group on day 29 (p < 0.001). No significant difference in body weight was noted between the E2 + DHT and oligonol-treated group (p = 0.952). (B) The E2 + DHT and oligonol-treated group showed significantly reduced prostate weight compared to the normal control group (p < 0.001). No significant difference in prostate weight was noted between the E2 + DHT and oligonol-treated group (p = 0.125). E2, 17 estradiol; DHT, dihydrotestosterone.

• 

  Fig. 3 Histopathologic findings of the prostate lateral lobe in 3 groups (hematoxylin and eosin stain, ×100). (A) The normal control group showed normal appearance of the glandular epithelium without leukocyte infiltration. All rats showed grade 0 inflammation. (B) In the E2 +DHT-treated group, extensive infiltration of inflammatory cells, including neutrophils, lymphocytes, macrophages, and degeneration of glandular epithelial cells, were found, suggesting CP. Eight rats showed grade 3 and 2 showed grade 2 inflammation. (C) In the oligonol-treated group, less inflammatory cells and degenerated epithelial cells were noted. Six rats showed grade 2 and 4 presented grade 1 inflammation. E2, 17 estradiol; DHT, dihydrotestosterone; CP, chronic prostatitis.

• 

  Fig. 4 Effect of E2 + DHT and oligonol on SOD activity in serum (A) and lateral lobe of prostate tissue (B). Each value represents mean ± SD. E2, 17 estradiol; DHT, dihydrotestosterone; SOD, superoxide dismutase. *Significantly different from the normal control group at p < 0.05.

• 

  Fig. 5 Effect of E2+DHT and oligonol on GPx activity in plasma (A) and lateral lobe of prostate tissue (B). Each value represents mean ± SD. E2, 17 estradiol; DHT, dihydrotestosterone. *Significantly different from the normal control group at p < 0.05. †Significantly different from the E2 + DHT-treated group at p < 0.05.

• 

  Fig. 6 Effect of E2 + DHT and oligonol on serum TNF-α level. Each value represents mean ± SD. E2, 17 estradiol; DHT, dihydrotestosterone; TNF-α, tumor necrosis factor-alpha. *Significantly different from the normal control group at p < 0.05.

• 

  Fig. 7 Effect of E2 + DHT and oligonol on IκBa phosphorylation. A: pIκBa and Iκ Ba expression using Western blotting analysis. B: pIκBa immunoblots were quantified by imaging densitometry with Image Gauge Software. E2, 17 estradiol; DHT, dihydrotes-tosterone; Od, optical density; Bkg, background. *The E2 + DHTtreated group presented significant increase of pIκBa compared to the normal control group (p < 0.05). †The oligonol-treated group showed significant decrease of pIκBa compared to the E2 + DHT-treated group (p < 0.05).

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