Chronic administration of the hydrogen sulfide prodrug SG1002 partially protects against erectile dysfunction resulting from long-term androgen deprivation
Abstract
Aims: Androgen deprivation therapy is a common treatment strategy for prostate cancer, although erectile dysfunction (ED) often coincides as an undesirable side-effect. Hydrogen sulfide (H2S) is an endogenous gasotransmitter with vasodilatory, anti-inflammatory, and antioxidant-like properties. H2S therapies are being developed for cardiovascular disease management, although the properties of H2S may also protect the erectile system.
Materials and methods: 14-week-old male C57Bl/6 mice were subjected to sham surgery or castration, with castrated mice remaining untreated or treated orally with low- or high-doses of the H2S prodrug SG1002 over the five-week intervention. Erectile function was assessed by intracavernous pressure and mean arterial pressure during cavernous nerve stimulation. Vascular reactivity of the corpus cavernosum (CC), internal pudendal artery (IPA), and internal iliac artery (IIA) were assessed by dose-dependent responses to vasodilatory, vasocontractile, and neurogenic stimuli in myograph systems. CC contents of proteins related to cellular autophagy, antioxidant defense, and mitochondrial dynamics were assessed by immunoblotting. Fibrotic remodeling was assessed by Masson's trichrome staining.
Key findings: SG1002 provided a moderate protection on erectile function against long-term androgen deprivation. Castration-induced alterations of several mechanisms of vasodilation and vasoconstriction of the CC and IPA were substantial, while alterations of the…
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