Effect of a phytotherapeutic agent, Eviprostat®, on prostatic and urinary cytokines/chemokines in a rat model of nonbacterial prostatitis.

BACKGROUND: Chronic inflammation in the prostate has recently been recognized as an important component of the symptom progression of benign prostatic hyperplasia. The objective of this study was to evaluate a range of cytokines/chemokines in prostate tissue and urine to identify markers of prostate inflammation in a prostatitis model and to investigate the effect of a phytotherapeutic agent, Eviprostat®, on these markers. METHODS: Ten-month-old male Wistar rats were divided into four groups. Nonbacterial prostatitis (NBP) was experimentally induced in groups 2-4 by castration followed by daily subcutaneous injection of 17ß-estradiol for 30 days. Control rats were fed a standard diet, while animals in the Eviprostat groups were fed a diet containing 0.05 or 0.1% Eviprostat for 30 days. The levels of cytokines/chemokines in prostate tissue on the 31st day and in urine collected the day before castration and the day before removal of the prostate were determined. RESULTS: Experimentally induced NBP increased the prostatic levels of the cytokines interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α). The levels of the chemokines CCL2/monocyte chemoattractant protein-1 (MCP-1), CCL3/macrophage inflammatory protein-1α (MIP-1α), CXCL1/CINC-1, CXCL3/CINC-2, and CXCL5/LIX were elevated in both prostate and urine. Eviprostat significantly suppressed the increases in prostate IL-1ß, TNF-α and CCL3/MIP-1α and prostatic and urinary CCL2/MCP-1 and CXCL1/CINC-1. CONCLUSIONS: Chemokines, including CCL2/MCP-1 and CXCL1/CINC-1, were elevated in the prostate and urine of NBP rats, and Eviprostat potently suppressed the increases in CCL2/MCP-1 and CXCL1/CINC-1. These chemokines are therefore candidate diagnostic biomarkers for nonbacterial chronic prostatic inflammation.

Short-term effects of TNP-470 in combination with cisplatin in the rat model of bladder cancer.

PURPOSE: To investigate the short-term effects of TNP-470 in combination with cisplatin in a rat model of bladder cancer. MATERIALS AND METHODS: Following treatment of TNP-470 with or without cisplatin for 7 days, the states of angiogenesis, apoptosis and cell proliferation were evaluated in rat bladder cancer induced by N-butyl-N-(4-hydroxybutyl) nitrosamine. RESULTS: In comparison with untreated tumors, we noted a significantly decreased microvessel density (MVD) in the rat bladder cancer treated by TNP-470, and a significantly increased apoptotic index (AI) when treated by cisplatin. In TNP-470 plus cisplatin-treated tumors, both significantly decreased MVD and increased AI were observed in non-invasive and invasive rat bladder cancers in addition to a significantly decreased proliferation index (PI) in invasive cancer. CONCLUSION: The combination therapy of TNP-470 with cisplatin may act through both the inhibition of angiogenesis and induction of apoptosis, and invasive tumor cells may be much more sensitive to this combined therapy in rat bladder cancer.