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Riluzole, a neuroprotective agent, preserves erectile function following bilateral cavernous nerve injury in male rats

International Journal of Impotence Research (2023)Cite this article

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Abstract

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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Fig. 1: RIL treatment improved CN electrical stimulation-induced erectile function 7 days after BCNI.
Fig. 2: RIL treatment improved CN electrical stimulation-induced erectile function 15 days after BCNI.
Fig. 3: RIL treatment for 15 days prevented the BCNI-induced decrease in p-PKC β IIser660 in the penile tissue.
Fig. 4: BCNI did not change the p-PKC β IIser660 in MPG.
Fig. 5: RIL treatment did not prevent the BCNI-induced decrease in EAAT-1 in the MPG.
Fig. 6: RIL treatment for 15 days prevented the BCNI-induced decrease in EAAT-2 in the MPG.

Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Funding

Funding

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.

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Authors and Affiliations

  1. Karadeniz Technical University, Faculty of Pharmacy, Department of Pharmacology, Trabzon, Türkiye

    Elif Nur Barut, Seckin Engin, Yesim Kaya Yasar & Sena F. Sezen

  2. Karadeniz Technical University, Drug and Pharmaceutical Technology Application and Research Center, Trabzon, Türkiye

    Yesim Kaya Yasar & Sena F. Sezen

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  1. Elif Nur Barut
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  2. Seckin Engin
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Contributions

Conceptualization: ENB, SFS. Methodology: ENB, SFS. Data curation, investigaton: ENB, SE, YKY, SFS. Funding acquisition: SFS. Writing original draft: ENB, SFS. Review & editing: ENB, SE, YKY, SFS.

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Correspondence to Elif Nur Barut.

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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

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