Suppression of bladder oxidative stress and inflammation by a phytotherapeutic agent in a rat model of partial bladder outlet obstruction.
OBJECTIVE
Ischemia/reperfusion injury is a major etiological factor in the progression of bladder dysfunction after partial bladder outlet obstruction and it is partly mediated by the generation of free radicals. The phytotherapeutic agent Eviprostat, a popular treatment for benign prostatic hyperplasia in Japan and Germany, has antioxidant and anti-inflammatory activity. We investigated the effect of Eviprostat on oxidative stress and inflammation in bladder dysfunction in a bladder outlet obstruction rat model.


METHODS
Bladder outlet obstruction was surgically induced in male rats by placing a rubber ring around the urethra. Rats with bladder outlet obstruction were administered daily oral Eviprostat or vehicle, while sham operated animals were treated with vehicle. On day 6 after surgery bladder weight, oxidative stress markers and proinflammatory cytokine levels as a measure of bladder inflammation, were determined and histological alterations noted. Functional contractility studies were performed with longitudinal bladder strips.


RESULTS
Bladder outlet obstruction led to a significant increase in bladder weight, oxidative stress markers and proinflammatory cytokine levels. Eviprostat significantly suppressed these increases without affecting bladder weight. Histological analysis showed increased detrusor muscle hypertrophy and increased numbers of collagen fibers with accompanying inflammatory infiltration in the bladder of vehicle treated bladder outlet obstruction animals. Eviprostat treatment was associated with suppression of these changes. Decreased responses of obstructed bladder strips to electrical stimulation and KCl were ameliorated by Eviprostat treatment.


CONCLUSIONS
Eviprostat mediated decrease of the increased oxidative stress and bladder inflammation caused by bladder outlet obstruction may contribute to the protection of bladder function.
Oka
Michiko
M
Research Laboratories, Nippon Shinyaku Co., Ltd., Kyoto, Japan. m.oka@po.nippon-shinyaku.co.jp
Fukui
Tomomi
T
Ueda
Makoto
M
Tagaya
Mitsuhiro
M
Oyama
Tatsuya
T
Tanaka
Mitsushi
M
D000818:Animals; D003556:Cystitis / Q000188:drug therapy* / Q000503:physiopathology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004338:Drug Combinations; D004979:Ethamsylate / Q000494:pharmacology*; D007150:Immunohistochemistry; D018836:Inflammation Mediators / Q000032:analysis; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D008517:Phytotherapy / Q000379:methods; D010936:Plant Extracts / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012680:Sensitivity and Specificity; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D001748:Urinary Bladder Neck Obstruction / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*
D016207:Cytokines; D004338:Drug Combinations; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D010936:Plant Extracts; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D004979:Ethamsylate; C010152:eviprostat