EFFECT OF CO,POST-TREATMENT WITH TADENAN(TAD) ON THE MICTURITION CHARACTERISTICS OF THE RAT STIMULATED WITH DIHYDROTESTOSTERONE(DHT)

 

Authors:

Y. Yoshimura, F. Bellamy, I. Perkash, CE, Constantinou

   

Institution:

SCI Center & Urology, Stanford University, CA & Fournier Laboratories, Dijion, FRANCE

     

Conference:

ICS 2000 Tampere

       

Type:

Informally Discussed Posters

         

Category:

Bladder Outlet Obstruction

                 

Aims of Study
Pre-treatment with oral TAD has been shown to possess a protective effect on bladder dysfunction. In the present paper, we evaluated the functional influence of co-treatment and post-treatment with oral TAD on the frequency/volume characteristics of micturition of conscious rats, stimulated with DHT to induce experimental prostate growth.

Methods
Studies were carried out over a period of 6 weeks using 40 SD male adult rats weighing 504ą22g. Animals were divided into 4 equal groups and treated daily with DHT(1.25mg/Kg/s.c. dissolved in sesame oil(SO) as vehicle) and TAD (100mg/Kg/p.o. dissolved in peanut oil(PO) as vehicle). Groups were defined as follows: [1]:Vehicle only; SO during week 1-2, PO during week 1-6; [2]:DHT in SO during week 1-2, PO during week 1-6. [3]:DHT in SO+TAD in PO during week 1-2, TAD in PO during week 3-6. [4]:DHT in SO during week 1-2, TAD in PO during week 3-6. Micturition characteristics were monitored every 2 weeks for 24 hours while the conscious rats were housed in metabolic chambers. Data were analyzed in terms of frequency(F), and max. volume per micturition(V). At the conclusion of the 6 weeks period, rats were killed and wet prostate weight measured. Values are meanąSE.

Results
The effect of treatment in the four groups on F is given by Figure 1 which shows that DHT produces a significant increase in F attaining maximum effect by the 4th week of observation. As shown by Figure 1, co-treatment with TAD, as well as post-treatment with TAD significantly (p<0.01)suppresses the effect of DHT at the 4th week of observation.

 

The corresponding values for V are shown below by in Figure 2. As indicated DHT produces a significant (p<0.05) decrease in V in comparison to baseline values. However when TAD is co-administered, the reduction in V is supressed and when TAD is post-administered the reduction in V is reversed.

 

Figure 3 shows the effect of treatment on the weight of the prostates showing that DHT produces a significant increase (p<0.05)in prostate weight compared to controls. As indicated, co-treatment with TAD, group3, significantly suppresses (p<0.05)prostate growth in comparison to DHT in SO; group2. Furthermore in comparison to DHT-treatment group2, post-treatment with TAD, group4, does not significantly change prostate weight.

Conclusion
These results clearly demonstrate that both the co- and post-treatment with oral TAD can significantly suppress the DHT-induced effects on the frequency/volume characteristics of micturition in the conscious rat. The most pronounced effect of TAD was observed in its influence on the frequency of micturition providing evidence to suggest amelioration of the "obstructive micturition characteristics" as induced by experimental prostate growth using DHT. Finally it is suggesting that, co-TAD but not post-TAD administration regresses DHT-induced prostate growth.

SUPPORTED BY FOURNIER LABORATORIES