(090) Hydrogen Sulfide Therapy Stimulates Cellular Antioxidant Defense and Reverses Erectile Dysfunction in Western Diet-fed Mice

Abstract Introduction Hydrogen sulfide (H2S) is an endogenously produced gaseous cellular signaling molecule with vasodilatory, anti-inflammatory, and antioxidant-like properties. H2S thought to protect against oxidative stress through activation of transcription factor(s) that transcribe genes involved detoxification antioxidant defense. We have previously used a Western diet (WD) high in fat sugar induce erectile dysfunction (ED) rodents, which excessive penile reactive oxygen species (ROS) been implicated ED pathogenesis. recently observed reduction protein content activity cystathionine γ-lyase, major enzymatic source H2S, the corpus cavernosum mice fed WD for 12 weeks. Objective The objective this study was determine if chronic consumption orally active, slow releasing prodrug (SG1002) can restore function alleviate WD-induced redox burden. Methods Young male C57Bl/6J (n = 120) were control (CD) or ad libitum 18 For final six weeks dietary intervention, half switched equivalent containing SG1002 at concentration designed deliver approximately 20 mg/kg/day. Following assessed by measuring intracavernosal pressure (ICP) mean arterial (MAP) during cavernous nerve stimulation (1, 2, 4 volts). In separate mice, vivo ROS production measured penis utilizing microdialysis approach. Microdialysis probes inserted into anesthetized perfused saline 100 μM Amplex Ultrared, 1 U/ml horseradish peroxidase, 10 superoxide dismutase. convert reagents fluorescent byproduct resorufin, outflowing dialysate. naïve tissue harvested quantitative expression related defense qRT-PCR. Significant differences between groups determined two-way ANOVA Tukey’s multiple comparisons post-hoc analysis, alpha level 0.05. Results Erectile significantly impaired untreated WD-fed (CD: 64.8±8.4 vs. WD: 27.1±2.3; cumulative ICP area/MAP; p<0.01), while induced 74% functional restoration (WD+SG1002: 51.0±2.8; p<0.05 WD). Penile hydrogen peroxide elevated 0.71±0.07 1.09 ±0.15; normalized treatment 0.83±0.07; p<0.01 had positive stimulatory effect (p<0.05) on ten genes, including catalase, glutamate-cysteine ligase (gclc), glutathione peroxidase 1, 4, peroxiredoxin 3, 5, thioredoxin reductase heme oxygenase sirtuin 3. Conclusions therapy administration provides protection burden high-fat/high-sugar environment diet, likely augmentation system. may be promising strategy early stage, obesity-associated dysfunction. Disclosure No