FTY720 Supplementation Partially Improves Erectile Dysfunction in Rats With Streptozotocin-Induced Type 1 Diabetes Through Inhibition of Endothelial Dysfunction and Corporal Fibrosis.

INTRODUCTION: Erectile dysfunction (ED) in patients with diabetes mellitus (DM) seriously affects their quality of life. However, these patients show a poor effect rate for oral phosphodiesterase type 5 inhibitors. Thus, new treatment methods are urgently needed. Fingolimod hydrochloride (FTY720) was approved in 2010 for the treatment of patients with the relapsing-remitting form of multiple sclerosis.

AIM: To investigate whether FTY720 supplementation could ameliorate ED induced by DM (DMED).

METHODS: Forty male Sprague-Dawley rats (8 weeks old) were used for the experiment. Thirty-two had type 1 DM induced by streptozotocin and the other eight rats constituted the control group. Eight weeks later, the erectile function of rats was assessed with an apomorphine test. Only some rats with DMED were treated with FTY720 orally every day for 4 weeks; the other rats remained in the same condition for 4 weeks.

MAIN OUTCOME MEASURE: Metabolic parameters; erectile function; sphingosine-1-phosphate receptor 3 (S1P3), protein kinase B (Akt), nitric oxide (NO), and cyclic guanosine monophosphate (cGMP) signaling pathway; corporal fibrosis; apoptosis level; and Smad and non-Smad signaling pathways.

RESULTS: There were no significant differences in the initial body weights and fasting glucose concentrations among the three groups. Erectile function in the DMED group was significantly impaired compared with the control group and was partly, but significantly, improved in the DMED + FTY720 group. The DMED group showed inhibited activity of the S1P3-Akt-NO-cGMP signaling pathway, and the inhibition was partly reversed in the DMED + FTY720 group. The DMED group showed serious corporal fibrosis, higher apoptosis level, higher ratio of Bax to Bcl-2, and higher expressions of the Smad pathway (transforming growth factor-β1, Smad, and connective tissue growth factor) and the non-Smad pathway (transforming growth factor-β1, rho-associated protein kinase, LIM domain kinase 2, and cofilin). However, FTY720 supplementation partly increased the ratio of smooth muscle to collagen, decreased the ratio of Bax to Bcl-2, and inhibited activity of the Smad and non-Smad pathways.

CONCLUSION: FTY720 supplementation inhibited endothelial dysfunction and corporal fibrosis, ultimately leading to partial improvement of DMED in rats. This finding provides evidence for a potential treatment method for DMED. Cui K, Ruan Y, Wang T, et al. FTY720 Supplementation Partially Improves Erectile Dysfunction in Rats With Streptozotocin-Induced Type 1 Diabetes Through Inhibition of Endothelial Dysfunction and Corporal Fibrosis. J Sex Med 2017;14:323-335.