Restoring Erectile Function by Antioxidant Therapy in Diabetic Rats

Hirata, Hiroshi; Kawamoto, Ken; Kikuno, Nobuyuki; Kawakami, Toshifumi; Kawakami, Kazumori; Saini, Sharanjot; Yamamura, Soichiro; Dahiya, Rajvir

doi:10.1016/j.juro.2009.07.009

Cited by 32 publications

(32 citation statements)

References 21 publications

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“…26 Additional studies have shown the potential use of ROS scavengers in salvaging erectile function in diabetic condition. 27,28 In corpora cavernosa from streptozotocin-induced diabetic rats, antioxidant treatment improves superoxide dismutase activity, increases endothelial nitric oxide synthase expression, and reduces ROS generation in corpora cavernosa, followed by an improvement in intracavernosal pressure/mean arterial pressure ratio. 29 Despite the evidence that DM is an important risk factor for ED, little is known about IPA function in diabetic conditions, and even less is known about the involvement of any catalytic core subunit of NOX, such as NOX1, in IPA function in DM.…”

mentioning

confidence: 99%

Internal Pudental Artery Dysfunction in Diabetes Mellitus Is Mediated by NOX1-Derived ROS-, Nrf2-, and Rho Kinase–Dependent Mechanisms

et al. 2016

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E rectile dysfunction (ED) is characterized by the inability to develop or maintain penile erection during sexual activity.1 In healthy subjects, penile erection depends on highly coordinated responses, involving relaxation of the pre-and intrapenile vasculature, leading to increased penile blood flow, increased intracavernosal pressure, and penile tumescence. 2,3 Arterial blood flow to the corpus cavernosum originates from the internal iliac arteries, courses to the internal pudendal arteries (IPA), and terminates in the bilateral cavernous arteries. Functional and structural changes in the IPA lead to ED. 4 Diabetes mellitus (DM) is an important risk factor for ED. Over 50% of men with DM develop ED. [5][6][7] In humans, DM is associated with stenosis and occlusion of IPA, which can compromise blood inflow to the corpora cavernosa and, consequently, impair erectile function. 8,9 Abnormalities in IPA are found in 36.7% of diabetic patients. 10 Although it may be expected that IPA display DM-associated dysfunction, 11 almost no studies have addressed the function of IPA in DM. 12 Hyperglycemia, hyperlipidemia, and inflammation, 3 main metabolic abnormalities in DM, induce reactive oxygen species (ROS) generation and oxidative stress. Oxidative stress, defined as a disturbance in the production of ROS or in the ability of the antioxidant defenses to neutralize ROS, is critically involved in DM-associated complications, including nephropathy, cardiomyopathy, endothelial dysfunction, and ED. 6,[13][14][15] Nicotinamide adenine dinucleotide phosphate-oxidase (NADPH oxidase) is the main source of ROS in the vasculature. Seven NADPH oxidase isoforms have been identified (NOX1-5, Duox1, Duox2), 16 with nicotinamide adenine dinucleoride phosphate oxidase 1 (NOX1) playing an important role in vascular smooth muscle cell (VSMC) proliferation, migration, and extracellular matrix production.17 IncreasedAbstract-Oxidative stress plays an important role in diabetes mellitus (DM)-associated vascular injury. DM is an important risk factor for erectile dysfunction. Functional and structural changes in internal pudendal arteries (IPA) can lead to erectile dysfunction. We hypothesized that downregulation of nuclear factor E2-related factor 2 (Nrf2), consequent to increased nicotinamide adenine dinucleotide phosphate oxidase 1 (NOX1)-derived reactive oxygen species (ROS), impairs IPA function in DM. IPA and vascular smooth muscle cells from C57BL/6 (control) and NOX1 knockout mice were used. DM was induced by streptozotocin in C57BL/6 mice. Functional properties of IPA were assessed using a myograph, protein expression and peroxiredoxin oxidation by Western blot, RNA expression by polymerase chain reaction, carbonylation by oxyblot assay, ROS generation by lucigenin, nitrotyrosine, and amplex red, and Rho kinase activity and nuclear accumulation of Nrf2 by ELISA. IPA from diabetic mice displayed increased contractions to phenylephrine (control 138.5±9.5 versus DM 191.8±15.5 Nuclear factor E2-related factor 2 (Nrf2) is the mai...

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mentioning

confidence: 99%

Internal Pudental Artery Dysfunction in Diabetes Mellitus Is Mediated by NOX1-Derived ROS-, Nrf2-, and Rho Kinase–Dependent Mechanisms

et al. 2016

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“…Experimentally-induced diabetic models are well-established to elaborate the mechanism of diabetic-induced ED and also a recommended model for establishing the beneficial effect of any new compound against diabetes ED [9]. In present study, sever sexual impairment was found in STZ-induced diabetic rat by inhibiting the EL, PEI, ML and IL latencies and increasing the MF and IF frequencies.…”

Section: Resultsmentioning

confidence: 48%

“…The superoxide dismutase (SOD) is also a vital enzyme that eradicates the superoxide radicals. However, increased production of ROS can inhibit SOD activity, which augment the peroxynitrite and ameliorate NO levels [9].…”

Section: Introductionmentioning

confidence: 99%

Improvement of sexual behavior, sperm quantity and quality by Quercetin in streptozotocin-induced diabetic erectile dysfunction

Alroujayee

2017

APJR

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“…Evidence has been presented verifying that DM also has a tight correlation with the apoptosis of various cell types, including the cavernous smooth muscle cells [40], corpus cavernosal endothelial cell [10]. Apoptosis is a basic programmed cell death process to maintain the dynamic balance of the cell environment.…”

Section: Discussionmentioning

confidence: 99%

Couplet medicines of leech and centipede granules improve erectile dysfunction via inactivation of the CaSR/PLC/PKC signaling in streptozotocin-induced diabetic rats

et al. 2020

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Erectile dysfunction (ED) is one of the significant complications of diabetes mellitus (DM), and CASR plays an important role in cellular antiapoptosis and NO production in the vascular endothelium by activating PKC. The present study was aimed to investigate the efficacy of Leech and Centipede Granules (LCG) through the CaSR/PLC/PKC signaling. Fifty male Sprague-Dawley rats were treated with streptozotocin to induce the DM model. After 10 weeks, an apomorphine test was used to confirm DMED. Rats with DMED were administrated with LCG and U73122 for 4 weeks. Fasting blood glucose, body weight, insulin and glucagon levels were measured. Erectile function in rats was assessed by apomorphine. Serums were measured using enzyme-linked immunosorbent assay and flow cytometry, and penile tissues were harvested for histologic and the expression of related targets analyses. After treatment, fasting blood glucose, body weight, insulin, glucagon levels, and erectile function were significantly ameliorated in the LCG groups. The LOX-1, NOX, and EMPs concentrations were significantly decreased with LCG treatment. LCG also continuously increased NO and decreased ET-1 content in penile tissues. LCG and U73122 administration also improved penile fibrosis by significantly decreasing VCAM-1, ICAM-1, and CD62P. The data also showed that LCG reduced the apoptosis level in the penis. Furthermore, the inhibited activation of the CaSR/PLC/PKC pathway was observed in DMED rats with LCG treatment. Collectively, LCG significantly ameliorated erectile function of DMED rats via increased NO generation, inhibiting endothelial cells apoptosis and penile fibrosis, which might benefit from the suppression of CaSR/PLC/PKC pathway in DMED rats.

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Restoring Erectile Function by Antioxidant Therapy in Diabetic Rats

Abstract: To our knowledge this is the first report that tempol and insulin can restore erectile function in diabetic rats by inhibiting apoptosis.

Cited by 32 publications

References 21 publications

Internal Pudental Artery Dysfunction in Diabetes Mellitus Is Mediated by NOX1-Derived ROS-, Nrf2-, and Rho Kinase–Dependent Mechanisms

Internal Pudental Artery Dysfunction in Diabetes Mellitus Is Mediated by NOX1-Derived ROS-, Nrf2-, and Rho Kinase–Dependent Mechanisms

Improvement of sexual behavior, sperm quantity and quality by Quercetin in streptozotocin-induced diabetic erectile dysfunction

Couplet medicines of leech and centipede granules improve erectile dysfunction via inactivation of the CaSR/PLC/PKC signaling in streptozotocin-induced diabetic rats

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