Depression induced by chronic stress leads to penile cavernosal dysfunction: protective effect of anti-TNF-α treatment

Şahin, Tuğçe Demirtaş; Yazır, Yusufhan; Utkan, Tijen; Gacar, Gülçin; Halbutoğulları, Zehra Seda; Göçmez, S.S.

doi:10.1139/cjpp-2017-0778

Cited by 14 publications

(9 citation statements)

References 40 publications

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“…In line with our results, siRNA-mediated knockdown of NgBR has been indicated to suppress survivin, an apoptosis inhibitor, in the context of breast cancer, the mechanism of which may be a potential marker for treatment modalities [9]. Decreased levels in ICAM-1 in rats with unpredictable chronic mild stress-induced ED have been suggested to be involved with the therapeutic effects of etanercept [15], which provides supporting evidence that the silencing of NgBR or down-regulation of ICAM-1 can be used to develop target treatments for ED.…”

Section: Discussionsupporting

confidence: 78%

“…There is a high expression in ICAM-1 in aging-related ED [14]. In addition, the expression of ICAM-1 has been observed to increase in penile cavernosal dysfunction that occurs as a result of chronic stress [15]. The ICAM-1 engagement has been shown to activate steroid receptor coactivator (SRC) and proline-rich tyrosine kinase2 (PYK2), both of which in return are recruited to the ICAM-1 engagement sites in human leukocytes and endothelial cells [16].…”

Section: Introductionmentioning

confidence: 99%

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Silencing Nogo-B receptor inhibits penile corpus cavernosum vascular smooth muscle cell apoptosis of rats with diabetic erectile dysfunction by down-regulating ICAM-1

et al. 2019

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Erectile dysfunction (ED) is a major sexual problem for men. Nogo-B receptor (NgBR) has been found to be involved in the regulation of vascular remodeling and angiogenesis. The present study explores the effects of NgBR in penile corpus cavernosum in rats with diabetic ED. Firstly, the ED model of Sprague Dawley rats was established. Hematoxylin-eosin staining and Masson staining were conducted to observe pathological morphology. Immunochemical assay was adopted to detect α-smooth muscle actin (α-SMA), NgBR and intercellular cell adhesion molecule-1 (ICAM-1) expression. Reverse transcription quantitative polymerase chain reaction assay and Western blot analysis were carried out for the assessment of NgBR, factors correlated to ICAM-1, including steroid receptor coactivator (SRC) and proline-rich tyrosine kinase2 (PYK2), and factors associated with apoptosis, including B-cell lymphoma-2 (Bcl-2), Bcl-2 associated protein X (Bax), caspase 3 and cleaved-caspase 3. The results found that capillaries and vascular smooth muscle cell content reduced, and NgBR and ICAM-1 were elevated in rats with diabetic ED. si-NgBR relieved ED by decreasing penile corpus cavernosum smooth muscle systolic percentage and increasing erectile time and rate, intracavernous pressure (ICP)/mean arterial pressure (MAP) and diastolic percentage, improving the pathological changes and inhibiting cavernosum cell apoptosis. si-NgBR also resulted in the down-regulation of ICAM-1 and downstream SRC and PYK2 and promoted α-SMA expression. In conclusion, si-NgBR can provide a potential therapy for diabetic ED in rats by down-regulating ICAM-1, SRC and PYK2, making it a potential therapeutic option for diabetic ED.

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Section: Discussionsupporting

confidence: 78%

Section: Introductionmentioning

confidence: 99%

Silencing Nogo-B receptor inhibits penile corpus cavernosum vascular smooth muscle cell apoptosis of rats with diabetic erectile dysfunction by down-regulating ICAM-1

et al. 2019

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“…In PAV group, it was observed in only 1 (12.5%) rat. As we know from the literature, inhibition of TNF alpha and proinflammatory cytokines, including IL-6, improves cavernosal inflammation and functions [22]. According to us, the decreased rates of inflammation in groups AV and PAV were probably due to anti-inflammatory effect of Aloe vera.…”

Section: Discussionmentioning

confidence: 80%

Histopathological effects of aloe vera on wound healing process in penile fracture model: an experimental study

Akgül¹,

Doğantekin²,

Özer³

et al. 2021

Turk J Med Sci

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Background/aim: This study assessed the histopathological effects of Aloe vera (AV) on penile fractures (PF) formed experimentally in rat model. Materials and methods:Thirty two Wistar adult male rats (220 to 250 g) were used. PF model was created experimentally with a number 15 lancet. After the interventions, all of the rats were randomly and equally divided into 4 groups. In the first group, incision was not closed (group C). In the second group, AV was locally applied onto incision without suturing for three days (group AV). In the third group, the incision line was closed primarily (group PR). In the last group, AV was applied to primary repair region for three days (group PAV). All groups were compared to each other according to presence of fibrosis, inflammation and hyperemia-bleeding.Results: Hyperemia and bleeding were seen in all groups with varying degrees and the difference between groups was insignificant (p=1.000). According to inflammation, there was significant difference between all groups (p=0.031). No significant inflammation was observed in group AV and therefore, group AV had a better score than group PR (p=0.026).In group PAV, inflammation was less seen than group PR, however, the difference was insignificant (p=0.119).According to fibrosis, group AV and group PAV had same fibrosis rates. Fibrosis was observed in 2 (25%) rats in each group. When group PR was compared with group AV and 2 group PAV, there were no significant differences according to cavernosal tissue healing with fibrosis (p= 0.132 and p=0.132, respectively). Conclusion:Local application of AV onto the PF region without closing with suture decreased inflammation in rats.

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“… 15 31 IL-1β, a potent proinflammatory cytokine, can impair cavernosum endothelial cells and lead to ED. 32 The NLRP3 inflammasome, composed of the NLRP3 protein, the adaptor protein ASC, and the cysteine protease pro-caspase-1, is an important regulator of the innate immune response, and its activation plays a crucial role in the pathogenesis of diabetes and diabetic complications. Diabetes-related mitochondrial dysfunction has been considered to be pivotal in this process.…”

Section: Discussionmentioning

confidence: 99%

The near-infrared dye IR-61 restores erectile function in a streptozotocin-induced diabetes modelvia mitochondrial protection

Yue

Shen

Wang

et al. 2021

Asian Journal of Andrology

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This study aimed to evaluate the therapeutic effect of IR-61, a novel mitochondrial heptamethine cyanine dye with antioxidant effects, on diabetes mellitus-induced erectile dysfunction (DMED). Eight-week-old male Sprague–Dawley rats were intraperitoneally injected with streptozotocin (STZ) to induce type 1 diabetes. Eight weeks after STZ injection, all rats were divided into three groups: the control group, DM group, and DM + IR-61 group. In the DM + IR-61 group, the rats were administered IR-61 (1.6 mg kg −1 ) twice a week by intravenous injection. At week 13, erectile function was evaluated by determining the ratio of the maximal intracavernous pressure to mean arterial pressure, and the penises were then harvested for fluorescent imaging, transmission electron microscopy, histological examinations, and Western blot analysis. Whole-body imaging suggested that IR-61 was highly accumulated in the penis after intravenous injection. IR-61 treatment significantly improved the maximal ICP of diabetic rats. Additionally, IR-61 ameliorated diabetes-induced inflammation, apoptosis, and phenotypic transition of corpus cavernosum smooth muscle cells (CCSMCs) in penile tissue. IR-61 also attenuated mitochondrial damage, reduced reactive oxygen species production in the corpus cavernosum and upregulated sirtuin1 (SIRT1), sirtuin3 (SIRT3), nuclear factor (erythroid-derived 2)-like 2 (Nrf2), and heme oxygenase expression in penile tissue. In conclusion, IR-61 represents a potential therapeutic option for DMED by protecting the mitochondria of CCSMCs, which may be mediated by activation of the SIRT1, SIRT3, and Nrf2 pathways.

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Depression induced by chronic stress leads to penile cavernosal dysfunction: protective effect of anti-TNF-α treatment

Cited by 14 publications

References 40 publications

Silencing Nogo-B receptor inhibits penile corpus cavernosum vascular smooth muscle cell apoptosis of rats with diabetic erectile dysfunction by down-regulating ICAM-1

Silencing Nogo-B receptor inhibits penile corpus cavernosum vascular smooth muscle cell apoptosis of rats with diabetic erectile dysfunction by down-regulating ICAM-1

Histopathological effects of aloe vera on wound healing process in penile fracture model: an experimental study

The near-infrared dye IR-61 restores erectile function in a streptozotocin-induced diabetes modelvia mitochondrial protection

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