scholarly journals Human Tissue Kallikrein 1 Improves Erectile Dysfunction of Streptozotocin-Induced Diabetic Rats by Inhibition of Excessive Oxidative Stress and Activation of the PI3K/AKT/eNOS Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-18
Author(s):  
Yang Luan ◽  
Kai Cui ◽  
Zhe Tang ◽  
Yajun Ruan ◽  
Kang Liu ◽  
...  

Objective. To investigate the protective effects and mechanisms of human tissue kallikrein 1 (hKLK1) on type 1 diabetes mellitus- (DM-) induced erectile dysfunction in rats. Materials and Methods. The homozygous transgenic rats (TGR) harboring the hKLK1 gene and age-matched wild-type Sprague Dawley rats (WTR) were involved, and intraperitoneal injection of streptozotocin was utilized to induce diabetes in rats. Forty-eight-week-old male rats were randomly divided into a WTR group, TGR group, diabetic WTR group (WTDM), diabetic TGR group (TGDM), and TGDM with HOE140 group (TGDMH), with eight rats in each group. Twelve weeks later, the erectile response of all rats was detected by cavernous nerve electric stimulation, and corpus cavernosums were harvested to evaluate the levels of cavernous oxidative stress (OS), apoptosis, fibrosis, and involved pathways. Moreover, cavernous smooth muscle cells (CSMC) and endothelial cells (EC) were primarily isolated to build a coculture system for a series of in vitro verification. Results. The hKLK1 gene only existed and was expressed in TGR. Compared to the WTR group, the WTDM group showed a lower erectile response, overactivated OS and apoptosis, inhibited PI3K/AKT/eNOS pathway, and aggravated cavernous fibrosis. However, hKLK1 in the TGDM group could improve these pathological changes induced by DM, while its protective effects could be weakened by HOE140 in the TGDMH group. In the coculture system, hKLK1 could induce CSMC relaxation through activating PI3K/eNOS/cGMP signaling and inhibiting calcium ion influx under physiological condition. It could also resist the increased reactive oxygen species, apoptosis level, and reduced cGMP level in CSMC under high-glucose condition. Conclusions. hKLK1 preserves erectile function of DM rats through its antitissue excessive OS, apoptosis, and fibrosis effects, as well as activation of the PI3K/AKT/eNOS/cGMP pathway in the penis. Moreover, hKLK1 promotes relaxation and prevents high glucose-induced injuries of CSMC mediated by EC-CSMC crosstalk.

2008 ◽  
Vol 13 (2) ◽  
pp. 84-89 ◽  
Author(s):  
Na-Ri Yi ◽  
Kyoung-Chun Seo ◽  
Ji-Myung Choi ◽  
Eun-Ju Cho ◽  
Young-Ok Song ◽  
...  

2016 ◽  
Vol 22 (4) ◽  
pp. 499-505 ◽  
Author(s):  
Hui Yan ◽  
Yongmei Li ◽  
Yali Yang ◽  
Zaijun Zhang ◽  
Gaoxiao Zhang ◽  
...  

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Watcharaporn Preedapirom ◽  
Kanokwan Changwichit ◽  
Piyarat Srisawang ◽  
Kornkanok Ingkaninan ◽  
Pornnarin Taepavarapruk

This study investigated the effect of Eulophia macrobulbon (EM) extract on sexual performance in aged-related erectile dysfunction (ED) rats. The ethanol EM extract at the doses of 15, 150, and 450 and sildenafil citrate at the dose of 5 mg/kg body weight (BW) were administered orally to the aged male rats once daily for 21 days. Mating parameters and intracavernosal pressure (ICP) were measured to evaluate their sexual and erection functions. Numbers of sperm and sperm motility as well as the diameter of seminiferous tubules were observed. The serum testosterone and 3’,5’-cyclic guanosine monophosphate (cGMP) concentration in the rat penile tissue were analyzed. The results showed the significant increased sexual motivation, copulatory performance, and ICP of aged rats treated with sildenafil citrate and all doses of EM extract as compared to control aged rats. Moreover, their serum testosterone levels were slightly increased and significant increase in penile cGMP concentration was observed in these aged rats treated with sildenafil citrate and EM extract. The results suggest that treatment with EM could inhibit activity of PDE5 in penile tissue resulting in the increased cGMP level and bring to the improvement of erectile function and sexual performance.


2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Kaifeng Li ◽  
Mengen Zhai ◽  
Liqing Jiang ◽  
Fan Song ◽  
Bin Zhang ◽  
...  

Hyperglycemia-induced oxidative stress and fibrosis play a crucial role in the development of diabetic cardiomyopathy (DCM). Tetrahydrocurcumin (THC), a major bioactive metabolite of natural antioxidant curcumin, is reported to exert even more effective antioxidative and superior antifibrotic properties as well as anti-inflammatory and antidiabetic abilities. This study was designed to investigate the potential protective effects of THC on experimental DCM and its underlying mechanisms, pointing to the role of high glucose-induced oxidative stress and interrelated fibrosis. In STZ-induced diabetic mice, oral administration of THC (120 mg/kg/d) for 12 weeks significantly improved the cardiac function and ameliorated myocardial fibrosis and cardiac hypertrophy, accompanied by reduced reactive oxygen species (ROS) generation. Mechanically, THC administration remarkably increased the expression of the SIRT1 signaling pathway both in vitro and in vivo, further evidenced by decreased downstream molecule Ac-SOD2 and enhanced deacetylated production SOD2, which finally strengthened antioxidative stress capacity proven by repaired activities of SOD and GSH-Px and reduced MDA production. Additionally, THC treatment accomplished its antifibrotic effect by depressing the ROS-induced TGFβ1/Smad3 signaling pathway followed by reduced expression of cardiac fibrotic markers α-SMA, collagen I, and collagen III. Collectively, these finds demonstrated the therapeutic potential of THC treatment to alleviate DCM mainly by attenuating hyperglycemia-induced oxidative stress and fibrosis via activating the SIRT1 pathway.


Molecules ◽  
2017 ◽  
Vol 22 (10) ◽  
pp. 1654 ◽  
Author(s):  
Bolajoko Ogunyinka ◽  
Babatunji Oyinloye ◽  
Foluso Osunsanmi ◽  
Andrew Opoku ◽  
Abidemi Kappo

2021 ◽  
Author(s):  
Mohammad Sheibani ◽  
Hedyeh Faghir-Ghanesefat ◽  
Yaser Azizi ◽  
Tahmineh Mokhtari ◽  
Hasan Yousefi‐Manesh ◽  
...  

The clinical use of doxorubicin as a potent chemotherapeutic agent is limited due to its dose-dependent cardiotoxicity. Oxidative stress and inflammatory pathways have a pivotal role in doxorubicin-induced cardiotoxicity. Sumatriptan, a 5-hydroxytryptamine (5-HT)1B/1D agonist that is mainly used to relieve migraine pain, has suggested exerting protective effects in numerous pathological conditions through antiinflammatory properties. The aim of the present study was to investigate the effects of sumatriptan on doxorubicin-induced cardiotoxicity and the contribution of anti-inflammation and antioxidative responses. Cardiotoxicity was induced by the administration of doxorubicin three times a week (2.5 mg/kg i.p) for two consecutive weeks on male rats. The animals were divided into four groups, including Control, Sumatriptan (0.1 mg/kg) received group, doxorubicin received group, and Doxorubicin+Sumatriptan (0.1 mg/kg) received group. Sumatriptan was administered 30 min before every injection of doxorubicin. On the last day of the second week, the body weight, mortality rate, electrocardiogram (ECG) and histopathological changes, cardiac inotropic study, and biochemical factors were evaluated. The loss of body weight, mortality rate, ECG parameters, reduction of papillary muscle contractility force as well as histopathological scores following administration of doxorubicin indicated severe cardiac damage. However, treatment with sumatriptan inhibited the functional and structural impairment induced by doxorubicin. In addition, sumatriptan could significantly reduce cardiac tissue levels of malondialdehyde (MDA) and tumor necrosis factor-alpha (TNF-α), which were increased in the doxorubicin-treated rats. This study illustrated the protective effects of sumatriptan on decreasing doxorubicin-induced cardiac toxicity and mortality rate in part through inhibition of inflammatory and oxidative stress pathways.


Reproduction ◽  
2020 ◽  
Vol 160 (6) ◽  
pp. 863-872 ◽  
Author(s):  
Joseph Bagi Suleiman ◽  
Victor Udo Nna ◽  
Zaida Zakaria ◽  
Zaidatul Akmal Othman ◽  
Ainul Bahiyah Abu Bakar ◽  
...  

Obesity and its accompanying complications predispose to abnormal testicular glucose metabolism, penile erectile dysfunction and subfertility. This study examined the potentials of orlistat in attenuating erectile dysfunction and fertility decline in high-fat diet (HFD)-induced obesity in male rats. Eighteen adult male Sprague–Dawley rats whose weights were between 250 and 300 g were divided into three groups (n = 6/group) namely: normal control (NC), HFD and HFD + orlistat (10 mg/kg body weight/day co-administered for 12 weeks) (HFD+O). During the 11th and 12th week, mating behaviour and fertility parameters were evaluated, and parameters of glucose metabolism were assessed at the end of the 12th week. Orlistat increased testicular mRNA levels of glucose transporters (Glut1 and Glut3), monocarboxylate transporters (Mct2 and Mct4) and lactate dehydrogenase type C (Ldhc), decreased intratesticular lactate and glucose levels, and LDH activity in obese rats. Furthermore, orlistat increased superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and glutathione reductase (GR) activities, and total antioxidant capacity (TAC), but decreased malondialdehyde level in the penis of obese rats. Similarly, orlistat improved penile cGMP level, sexual behaviour and fertility outcome in obese rats. Penile cGMP level correlated positively with total mounts and intromissions but correlated negatively with mount/intromission ratio. Orlistat improves fertility potential in obese state by targeting testicular lactate metabolism, penile oxidative stress and sexual behaviour in rats. Therefore, orlistat shows a promising protective effect and may preserve the fertility potential of obese men.


2020 ◽  
Vol 10 ◽  
Author(s):  
Batool Shakiba ◽  
Azam Moghani ◽  
Marzieh Kafami ◽  
Mahmoud Hosseini ◽  
Masoud Hosseinzadeh ◽  
...  

Background & Objective: Barley is widely used as a major staple of human food and animal feed. Several antioxidant phenols are found in barely, which have scavenging properties. The present study aimed to assess the protective effects of barley seed against the oxidative damage of brain tissues in a scopolamine-induced memory impairment model. Materials and Methods: In total, 32 male albino rats (mean weight: 250±10 g) were divided into four groups of saline (control), scopolamine, barley seed (100 mg/kg) with scopolamine, and barley seed alone. The spatial memory function was assessed using the Morris water maze. Results: Compared to the scopolamine group, barley seed could decrease the escape latency time in the treated rats, while the time spent and distance traveled in the target quadrant on the probe trial increased. Moreover, barley seed could increase the malondialdehyde concentration in the hippocampus and cortical tissues, while the thiol content was observed to decrease. Conclusion: According to the results, the use of dietary barley seed could improve the memory function in dementia associated with increased oxidative stress.


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