Effects of Unilateral Ischemia on the Contractile Response of the Bladder: Protective Effect of Tadenan (Pygeum africanum Extract).
Recent studies indicate that localized (regional) ischemia may play an important role in the etiology of the contractile dysfunctions secondary to partial outlet obstruction. Pretreatment with Tadenan® (Pygeum africanum extract) has been shown to protect the rabbit bladder against the development of both contractile and biochemical dysfunctions induced by partial outlet obstruction, possibly by protecting the bladder against ischemic injury. The current study was designed to determine if Tadenan pretreatment of rabbits protected the bladder against the development of contractile dysfunctions induced by unilateral ischemia and to correlate effects in the presence and absence of Tadenan with the molecular response in relation to two of the most prominent genes activated by both ischemia and partial outlet obstruction: Hsp-70 and c-myc. Male New Zealand rabbits were separated into four groups of six rabbits each. Three rabbits of each group were treated for 3 weeks with Tadenan. The other three rabbits of each group were untreated controls. Each rabbit in Groups 2, 3, and 4 was anesthetized, and all major arteries entering on the right side of the bladder were li-gated. Rabbits in Group 1 were nonischemic. After 30, 60, and 120 minutes of unilateral ischemia, the rabbits in groups 2, 3, and 4, respectively, were euthanized. The bladders were removed, and contractility studies were performed on strips of detrusor muscle isolated from both the ischemia and nonischemic sides. The balance of the ischemic and nonischemic sides were frozen and stored in liquid nitrogen until analyzed for the expression of Hsp-70 and for c-myc. Tadenan pretreatment protected the nonischemic side of the bladder from the development of contractile dysfunctions, and unilateral ischemia resulted in a 10-fold increase in the expression of both Hsp-70 and c-myc in the bladders isolated from the Tadenan-treated rabbits. These results indicate that Tadenan has a protective effect against ischemic damage to the bladder. This protection may involve enhanced expression of Hsp-70 and other genetic factors.
Chen
MW
Department of Urology, Columbia School of Medicine, New York, NY.
Levin
RM
Horan
P
Buttyan
RB