The role of apoptosis and the effect of epidermal growth factor (EGF) on pro-apoptotic BNIP-3 in the experimental priapism rat model

Priapism, which is described as prolonged erection without any sexual stimulus is clinically classified in three groups as low-flow, high-flow and stuttering priapism. By low flow priapism which is also described as ischemic priapism, irreversible erectile dysfunction may result due to impairment of the cavernousal smooth muscle therefore it is accepted as an urological emergency. It is reported that various types of growth factors could play a role in this ischemic apoptosis induced erectile dysfunction. In this experimental study the efficacy of apoptosis inducing Bcl-2/adenovirüs E1B 19 kDa-interacting protein 3 (BNIP-3) and Epidermal Growth Factor (EGF) with its antiapoptotic effect in the pathophysiology of low-flow priapism is researched.Twenty-four adult Sprague-Dawley rats divided into 4 equal groups were included to the study in order to realize the experimental ischemic priapism model. Group I is accepted as the control group, ischemic priapism is achieved and maintained for 4 hours in the group II. In the group III and IV EGF was intraperitonealy admitted during 7 days in 10 mcg/kg and 20 mcg/kg doses respectively before achieving the 4 hours lasting priapism status. After spontaneous regression of erection in the control and 4 hours of priapism in the other groups the rats were decapitated and en-bloc penis excision was performed. BNIP-3 expression level and the cells in the apoptotic phase were determined respectively by using Western Blot and TUNEL method in the cavernousal tisssue samples.By comparing the groups in regard to the BNIP-3 expression levels it was detected that Group II had the highest and Group IV with intraperitoneal 20 mcg/kg EGF application for 7 days the lowest level with 120,7 ± 1, 68 and 102,9 ± 1,56 respectively among all groups. Although the BNIP-3 expression level increase in all three study groups is statistically significant higher than the control group it was detected that BNIP-3 expression level was statistical significantly lower in the study groups with EGF admission than Group II (p<0,05). By the analysis of the study groups regarding the apoptosis extension level the lowest apoptosis rate was detected by Group IV.The antiapoptotic therapy methods regarding the protection of the cavernousal smooth muscle structure in ischemic priapism which may result in various levels of erectile dysfunction due to the duration of the ischemic status, are new aspects of research. The decrease in apoptosis in the cavernousal tissue as a result of the antagonisation of the apoptotic agent BNIP-3 with EGF could lead to development of new therapy methods through these pathways.Keywords: Ischemic priapism, Apoptosis, BNIP-3, EGF