Neurogenic erectile dysfunction is a highly prevalent complication in men undergoing radical prostatectomy. The underlying mechanisms remain incompletely defined and the effective therapy has been limited. This study aimed to evaluate the protective effect of riluzole and the role of PKC β and excitatory amino acid transporters (EAATs) mediating this effect in a rat model of bilateral cavernous injury (BCNI). A total of 48 male Sprague-Dawley rats were divided into sham, BCNI (at 7, 15 days post-injury) and BCNI treated with riluzole (8 mg/kg/day) groups. Erectile function was measured as maximum intracavernosal pressure (mICP)/mean arterial pressure (MAP) and total ICP/MAP. Changes in protein expressions of phospho (p)-PKC β IIser660 and EAATs were analysed in penis and major pelvic ganglion with western blotting. BCNI decreased erectile function at 7 and 15 days post-injury (mICP/MAP at 4 V: 0.45 ± 0.06 vs 0.84 ± 0.07; 0.34 ± 0.04 vs 0.77 ± 0.04 respectively; p < 0.001) whereas riluzole treatment (for 15 days) preserved erectile function (mICP/MAP at 4 V: 0.62 ± 0.03 vs 0.34 ± 0.04; p < 0.01). The decline in the expression of p-PKC β IIser660 was observed in penis at 7 and 15 days post-injury (p = 0.0003, p = 0.0033), which was prevented by riluzole treatment for 15 days (p = 0.0464). While expressions of EAAT-1 and EAAT-2 decreased in major pelvic ganglion following BCNI (p = 0.0428, p = 0.002), riluzole treatment for 15 days prevented the decrease only in EAAT-2 expression (p = 0.0456). Riluzole improved erectile function via possibly interacting with PKC β II and glutamatergic pathways, as a potential therapeutic candidate for erectile dysfunction.
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The data that support the findings of this study are available from the corresponding author upon reasonable request.
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This study was supported by the Scientific Research Project Coordination Unit of Karadeniz Technical University (Grant Number: TDK-2018-7672) and presented as a part of doctoral thesis.
The authors declare no competing interests.
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Barut, E.N., Engin, S., Yasar, Y.K. et al. Riluzole, a neuroprotective agent, preserves erectile function following bilateral cavernous nerve injury in male rats. Int J Impot Res (2023). https://doi.org/10.1038/s41443-023-00680-x