Eviprostat suppresses proinflammatory gene expression in the prostate of rats with partial bladder-outlet obstruction: a genome-wide DNA microarray analysis.
Prostatic inflammation plays a role in the progression of benign prostatic hyperplasia (BPH). Eviprostat is an antioxidant, antiinflammatory phytotherapeutic agent widely used to treat lower urinary tract symptoms in BPH. Because Eviprostat is a mixture of compounds from multiple natural sources, however, its mechanism of action has been difficult to investigate. Here, we describe the use of oligonucleotide microarrays to investigate changes in gene expression in the prostate of rats with surgically induced partial bladder-outlet obstruction and the effect of Eviprostat on those changes. Several dozen proinflammatory genes were activated in obstructed rats, including cytokine, arachidonic acid cascade enzyme, Toll-like receptor (TLR), and transcription factor genes, and their expression was suppressed by Eviprostat. Pathway analysis revealed that several proinflammatory pathways were activated, including cytokine and TLR signaling pathways. The differential expression of selected genes was verified by real-time reverse-transcriptase polymerase chain reaction. Our findings suggest that prostate inflammation in our rat model of partial bladder-outlet obstruction is related to the increased expression of nuclear factor kappaB (NF-kappaB) and the induction of proinflammatory cytokines, and that Eviprostat suppresses their expression at the transcriptional level. The prostate inflammation seen in BPH and the clinical benefits of Eviprostat may be similarly explained.
Tagaya
Mitsuhiro
M
Discovery Research Laboratories, Nippon Shinyaku Co., Ltd., 14, Nishinosho-monguchi-cho, Kisshoin, Minami-ku, Kyoto 601-8550, Japan. m.tagaya@po.nippon-shinyaku.co.jp
Oka
Michiko
M
Ueda
Makoto
M
Takagaki
Kazuchika
K
Tanaka
Mitsushi
M
Ohgi
Tadaaki
T
Yano
Junichi
J
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D016000:Cluster Analysis; D004338:Drug Combinations; D004979:Ethamsylate / Q000494:pharmacology*; D020869:Gene Expression Profiling; D016678:Genome; D018836:Inflammation Mediators / Q000378:metabolism*; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D010936:Plant Extracts / Q000494:pharmacology*; D011467:Prostate / Q000187:drug effects* / Q000378:metabolism; D011472:Prostatitis / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D001743:Urinary Bladder / Q000601:surgery
D000893:Anti-Inflammatory Agents; D004338:Drug Combinations; D018836:Inflammation Mediators; D010936:Plant Extracts; D004979:Ethamsylate; C010152:eviprostat