Long-term administration of resveratrol and MitoQ stimulates cavernosum antioxidant gene expression in a mouse castration model of erectile dysfunction

Abstract

Aims: Erectile dysfunction is a common complication within many pathological conditions associated with low testosterone. Testosterone deficiency increases oxidative stress in the penile tissue that contributes to endothelial dysfunction and subsequent erectile dysfunction. Current therapies do not ameliorate oxidative stress so targeting oxidative stress may improve erectile dysfunction. Resveratrol and MitoQ are two prospective drugs that have antioxidant-like properties and may be useful to improve erectile dysfunction induced by androgen deprivation.

Materials and methods: We castrated 12-week-old male C57BL/6 mice and performed an eight-week intervention with oral delivery of resveratrol or MitoQ at low and high doses. We assessed vascular reactivity of the corpus cavernosum and internal pudendal arteries (IPA) through dose-dependent responses to vasodilatory, vasocontractile, and neurogenic stimuli in a myograph system. We performed qRT-PCR to measure expression changes of 18 antioxidant genes in the corpus cavernosum.

Key findings: Castration significantly impaired erectile function via impaired endothelial-dependent and-independent relaxation, and increased constriction of the corpus cavernosum, and induced severe endothelial dysfunction of the IPA. Castration decreased expression of 8 of the antioxidant genes investigated. Resveratrol and MitoQ were ineffective in reversing the effects of androgen deprivation on vascular reactivity, however high-dose resveratrol treatment upregulated several key antioxidant genes, including Cat, Sod1, Gstm1, and Prdx3.

Significance: Our findings suggest that oral resveratrol and MitoQ treatment may provide protection to the corpus cavernosum under androgen deprived conditions by stimulating endogenous antioxidant systems. However, they may need to be paired with vasoactive drugs to reverse erectile dysfunction under androgen deprived conditions.

Keywords: Internal pudendal artery; Mitochondria; Myograph; Nrf2; Oxidative stress; Testosterone.