Probucol Improves Erectile Function by Restoring Endothelial Function and Preventing Cavernous Fibrosis in Streptozotocin-induced Diabetic Rats

Zhang, Ke‐Qin; Chen, Dong; Sun, Dawei; Zhang, Hui; Li, Bo; Fu, Qiang

doi:10.1016/j.urology.2016.02.004

Cited by 15 publications

(11 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Endothelial dysfunction of corpus cavernosum tissue is related to the decrease of NO production and impairment of NO activity, which may result in ED (Zuo et al ., ; Pomeshkin et al ., ; Bertoluci et al ., ; Pan et al ., ). The cGMP is known as an important component in penile erection, which is positively correlated with NO production (Zhang et al ., ). In this study, cGMP and eNOS expression levels all decreased significantly in EAP rats compared with normal controls, and it is demonstrated that CP/CPPS impaired endothelial function via eNOS/NO/cGMP signaling pathway.…”

Section: Discussionmentioning

confidence: 97%

“…ED is usually characterized by the loss of corporal smooth muscle cells within the corpus cavernosum, replacement of these cells with collagen and resulting in the increase of corporal fibrosis (Ferrini et al ., , ; Zhang et al ., ). Corporal fibrosis plays a key role in the deterioration of ED, which decreases penile elasticity and compliance.…”

Section: Discussionmentioning

confidence: 97%

See 1 more Smart Citation

Chronic prostatitis/chronic pelvic pain syndrome impairs erectile function through increased endothelial dysfunction, oxidative stress, apoptosis, and corporal fibrosis in a rat model

Niu

Wang

et al. 2016

Andrology

View full text Add to dashboard Cite

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is an independent risk factor for the development of erectile dysfunction (ED). But the molecular mechanisms underlying the relationship between CP/CPPS and ED are still unclear. The aim of this study was to investigate the effect of CP/CPPS on erectile function in a rat model and the possible mechanisms. A rat model of experimental autoimmune prostatitis (EAP) was established to mimic human CP⁄CPPS. Then twenty 2-month-old male Sprague-Dawley rats were divided into EAP group and control group. Intracavernosal pressure (ICP) and mean arterial pressure (MAP) were measured during cavernous nerve electrostimulation, the ratio of max ICP/MAP was calculated. Blood was collected to measure the levels of serum C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6) and testosterone, respectively. The expression of endothelial nitric oxide synthase (eNOS), cyclic guanosine monophosphate (cGMP) levels, superoxide dismutase (SOD) activity and malondialdehyde (MDA) levels in corpus cavernosum were detected. We also evaluated the smooth muscle/collagen ratio and apoptotic index (AI). The ratio of max ICP/MAP in EAP group were significantly lower than that in control group. The levels of serum CRP, TNF-α, IL-1β, and IL-6 in EAP group were all significantly higher than these in control group. The expression of eNOS and cGMP levels in corpus cavernosum of EAP rats were significantly downregulated. Furthermore, decreased SOD activity and smooth muscle/collagen ratio, increased MDA levels and AI were found in corpus cavernosum of EAP rats. In conclusion, CP/CPPS impaired penile erectile function in a rat model. The declines of eNOS expression and cGMP levels in corpus cavernosum may be an important mechanism of CP/CPPS-induced ED. CP/CPPS also increased oxidative stress, cell apoptosis and decreased smooth muscle/collagen ratio in corpus cavernosum of rats, which were all important for erectile function.

show abstract

Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 97%

Chronic prostatitis/chronic pelvic pain syndrome impairs erectile function through increased endothelial dysfunction, oxidative stress, apoptosis, and corporal fibrosis in a rat model

Niu

Wang

et al. 2016

Andrology

View full text Add to dashboard Cite

show abstract

“…Fibrosis has been believed to contribute to DMED. Many factors, including long‐term hyperglycemia damage and injury to penile nerve, can cause fibrosis of the corpus cavernosum in patients with DM, and fibrosis is characterized by smooth muscle reduction and collagen accumulation in the corpus cavernosum . In this study, we detected α‐SMA (a marker of CSMCs), collagen I, and collagen III in Western blots and found that after simvastatin treatment, these proteins of DMED tended to be similar to normal rats.…”

Section: Discussionmentioning

confidence: 58%

Simvastatin alleviated diabetes mellitus‐induced erectile dysfunction in rats by enhancing AMPK pathway‐induced autophagy

Fan

Shan

et al. 2020

Andrology

View full text Add to dashboard Cite

Background: Diabetes mellitus-induced erectile dysfunction is a common diabetic complication, and new therapeutics and the pathogenesis of diabetes mellitus-induced erectile dysfunction need to be investigated. Objectives:The aim was to investigate the pathogenesis of diabetes mellitus-induced erectile dysfunction and the pharmacological mechanism of simvastatin treatment in diabetes mellitus-induced erectile dysfunction model rats. Materials and methods:A total of 86 male Sprague Dawley rats aged 8 weeks old were used in this study. The rats were divided into three groups: control (normal), diabetes mellitus-induced erectile dysfunction (streptozotocin-injected), and diabetes mellitus-induced erectile dysfunction + simvastatin (sim). Each group was subdivided into two subgroups for in vitro and in vivo analyses. A bioinformatics method was used to detect differences in gene expression in the corpus cavernosum between normal and diabetes mellitus-induced erectile dysfunction rats. Erectile function was measured by a cavernous nerve electrostimulation test. Corpus cavernosum fibrosis was assessed by Masson staining and Western blotting. Immunofluorescence and Western blotting were performed to explore the differential expression of autophagy-related genes and the AMPK-SKP2-CARM1 pathway genes in rat cavernous smooth muscle cells and the corpus cavernosum. The autophagosomes of the corpus cavernosum tissue were observed by transmission electron microscopy. Results:Autophagy-related genes and pathways (the AMPK and FoxO pathway) were identified by bioinformatics analysis and confirmed at the protein level. Simvastatin, an AMPK agonist, was used to treat diabetes mellitus-induced erectile dysfunction rats for 8 weeks, demonstrating that erectile function was improved for 80.5% (P < .05) of rats. Corpus cavernosum fibrosis was alleviated (P < .05), and autophagy was further enhanced (P < .05); these results might be partially caused by AMPK-SKP2-CARM1 pathway activation (P < .05). Discussion and conclusion:Simvastatin could enhance protective autophagy by activating the AMPK-SKP2-CARM1 pathway to improve erectile function in diabetes mellitus-induced erectile dysfunction rats. | 781DING et al.

show abstract

“…Eventually, foam cells form, leading to the atherosclerotic lesions in the penile vasculature [15,16]. In addition, TNF-α can inhibit the expression of cGMP through NF-κB pathway [17], and decreased cGMP will inhibit the relaxation of smooth muscle cells [18].…”

Section: Discussionmentioning

confidence: 99%

Corpus cavernosum smooth muscle cell dysfunction and phenotype transformation are related to erectile dysfunction in prostatitis rats with chronic prostatitis/chronic pelvic pain syndrome

Wang

Huang

et al. 2020

J Inflamm

View full text Add to dashboard Cite

Background: The relationship between chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and erectile dysfunction (ED) has been shown in many studies. However, the specific mechanism remains unclear. This study was to investigate the corpus cavernosum smooth muscle cell function and phenotype transformation in Experimental autoimmune prostatitis (EAP) rats. Methods: EAP was induced in rats by using prostate protein supplemented with immuneadjuvant extraction, and the max-ICP and MAP were measured. IHC and Masson staining were done to assess inflammatory infiltration and collagen deposition in the corpus cavernosum, respectively. Subsequently, normal rat and EAP rat CCSMCs were purified by tissue block implantation and differential adherence method. The oxidative stress, smooth muscle phenotype transformation, cell cycle and intracellular calcium ion transport were also evaluated. Results: The ratio of max ICP/MAP in EAP rats significantly reduced, and the TNF-α content and collagen deposition in the corpus cavernosum markedly increased as compared to healthy rats. High-purity rat CCSMCs were obtained. Oxidative stress was evident and the cGMP content decreased in the EAP rat CCSMCs. The expression of Cav1.2, IP3R1 and RyR2 increased, but the SERCA2 expression decreased in EAP rat CCSMCs, which was accompanied by increased intracellular calcium. Increased expression of OPN, collagen and KCa3.1, decreased Calponin expression and increased proportion of cells in the S phase were also observed in the EAP rat CCSMCs. Conclusion: CP causes oxidative stress and imbalance of intracellular calcium in CCSMCs and promotes CCSMCs transformation from contractile to synthetic state, which may be involved in the pathogenesis of ED.

show abstract

Probucol Improves Erectile Function by Restoring Endothelial Function and Preventing Cavernous Fibrosis in Streptozotocin-induced Diabetic Rats

Cited by 15 publications

References 22 publications

Chronic prostatitis/chronic pelvic pain syndrome impairs erectile function through increased endothelial dysfunction, oxidative stress, apoptosis, and corporal fibrosis in a rat model

Chronic prostatitis/chronic pelvic pain syndrome impairs erectile function through increased endothelial dysfunction, oxidative stress, apoptosis, and corporal fibrosis in a rat model

Simvastatin alleviated diabetes mellitus‐induced erectile dysfunction in rats by enhancing AMPK pathway‐induced autophagy

Corpus cavernosum smooth muscle cell dysfunction and phenotype transformation are related to erectile dysfunction in prostatitis rats with chronic prostatitis/chronic pelvic pain syndrome

Contact Info

Product

Resources

About