Tetrathiomolybdate Partially Alleviates Erectile Dysfunction of Type 1 Diabetic Rats Through Affecting Ceruloplasmin/eNOS and Inhibiting Corporal Fibrosis and Systemic Inflammation

Introduction: Patients with erectile dysfunction induced by diabetes mellitus (DMED) show a poor effect rate for oral phosphodiesterase type 5 inhibitors (PDE5is). Therefore, the new therapeutic strategy is necessary in patients with DMED. Aim: To investigate whether Tetrathiomolybdate (TM) suppleme...

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Autores principales: Yinghao Yin, MS, Jingxuan Peng, MS, Jun Zhou, MS, Hanfei Chen, MS, Dongyi Peng, PhD, Dongjie Li, PhD, Yu Gan, PhD, Guangming Yin, PhD, Yuxin Tang, PhD
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Publicado: Elsevier 2022
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spelling oai:doaj.org-article:288fc032c5c945c9aee31c19a0d4e9af2021-11-24T04:28:18ZTetrathiomolybdate Partially Alleviates Erectile Dysfunction of Type 1 Diabetic Rats Through Affecting Ceruloplasmin/eNOS and Inhibiting Corporal Fibrosis and Systemic Inflammation2050-116110.1016/j.esxm.2021.100455https://doaj.org/article/288fc032c5c945c9aee31c19a0d4e9af2022-02-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2050116121001355https://doaj.org/toc/2050-1161Introduction: Patients with erectile dysfunction induced by diabetes mellitus (DMED) show a poor effect rate for oral phosphodiesterase type 5 inhibitors (PDE5is). Therefore, the new therapeutic strategy is necessary in patients with DMED. Aim: To investigate whether Tetrathiomolybdate (TM) supplementation could ameliorate DMED by activation of eNOS. Methods: Twenty-four diabetic rats were induced by intraperitoneal injection of streptozotocin (STZ) and the other 6 normal rats constituted the control group. Eight weeks later, the erectile function of rats was assessed with an apomorphine test. Only some rats with DMED were treated with TM orally every day for 4 weeks; the other rats remained in the same condition for 4 weeks. After 1 week washout, the erectile function of rats in each group was evaluated. Then, the serum concentration of IL-6 and histologic changes of corpus cavernosum were measured. Main Outcome Measure: Erectile function was measured after DMED rats treated with TM. The cavernosum level of Ceruloplasmin (Cp), eNOS, endothelial cell content, corporal fibrosis, apoptosis rate and the serum level of IL-6 were also assayed. Results: Erectile function in the DMED group was significantly impaired compared with the control group and was partly, but significantly, improved in the DMED+TM group. The DMED group showed upregulation of Cp and inhibition of eNOS, but the inhibition was partly reversed in the DMED+TM group. The DMED group showed serious corporal fibrosis. However, TM supplementation partly increased the ratio of smooth muscle to collagen, decreased the ratio of apoptosis. What's more, gavage administration of TM profoundly decreased the serum level of IL-6 in DMED rats. Conclusion: TM supplementation inhibits endothelial dysfunction, corporal fibrosis, and systemic inflammation, ultimately leading to partial improvement of DMED in rats.Yin Y, Peng J, Zhou J, et al., Tetrathiomolybdate Partially Alleviates Erectile Dysfunction of Type 1 Diabetic Rats Through Affecting Ceruloplasmin/eNOS and Inhibiting Corporal Fibrosis and Systemic Inflammation. Sex Med 2021;XX:XXXXXX.Yinghao Yin, MSJingxuan Peng, MSJun Zhou, MSHanfei Chen, MSDongyi Peng, PhDDongjie Li, PhDYu Gan, PhDGuangming Yin, PhDYuxin Tang, PhDElsevierarticleTetrathiomolybdateDiabetes MellitusErectile DysfunctionCeruloplasmineNOSMedicineROther systems of medicineRZ201-999ENSexual Medicine, Vol 10, Iss 1, Pp 100455- (2022)
institution DOAJ
collection DOAJ
language EN
topic Tetrathiomolybdate
Diabetes Mellitus
Erectile Dysfunction
Ceruloplasmin
eNOS
Medicine
R
Other systems of medicine
RZ201-999
spellingShingle Tetrathiomolybdate
Diabetes Mellitus
Erectile Dysfunction
Ceruloplasmin
eNOS
Medicine
R
Other systems of medicine
RZ201-999
Yinghao Yin, MS
Jingxuan Peng, MS
Jun Zhou, MS
Hanfei Chen, MS
Dongyi Peng, PhD
Dongjie Li, PhD
Yu Gan, PhD
Guangming Yin, PhD
Yuxin Tang, PhD
Tetrathiomolybdate Partially Alleviates Erectile Dysfunction of Type 1 Diabetic Rats Through Affecting Ceruloplasmin/eNOS and Inhibiting Corporal Fibrosis and Systemic Inflammation
description Introduction: Patients with erectile dysfunction induced by diabetes mellitus (DMED) show a poor effect rate for oral phosphodiesterase type 5 inhibitors (PDE5is). Therefore, the new therapeutic strategy is necessary in patients with DMED. Aim: To investigate whether Tetrathiomolybdate (TM) supplementation could ameliorate DMED by activation of eNOS. Methods: Twenty-four diabetic rats were induced by intraperitoneal injection of streptozotocin (STZ) and the other 6 normal rats constituted the control group. Eight weeks later, the erectile function of rats was assessed with an apomorphine test. Only some rats with DMED were treated with TM orally every day for 4 weeks; the other rats remained in the same condition for 4 weeks. After 1 week washout, the erectile function of rats in each group was evaluated. Then, the serum concentration of IL-6 and histologic changes of corpus cavernosum were measured. Main Outcome Measure: Erectile function was measured after DMED rats treated with TM. The cavernosum level of Ceruloplasmin (Cp), eNOS, endothelial cell content, corporal fibrosis, apoptosis rate and the serum level of IL-6 were also assayed. Results: Erectile function in the DMED group was significantly impaired compared with the control group and was partly, but significantly, improved in the DMED+TM group. The DMED group showed upregulation of Cp and inhibition of eNOS, but the inhibition was partly reversed in the DMED+TM group. The DMED group showed serious corporal fibrosis. However, TM supplementation partly increased the ratio of smooth muscle to collagen, decreased the ratio of apoptosis. What's more, gavage administration of TM profoundly decreased the serum level of IL-6 in DMED rats. Conclusion: TM supplementation inhibits endothelial dysfunction, corporal fibrosis, and systemic inflammation, ultimately leading to partial improvement of DMED in rats.Yin Y, Peng J, Zhou J, et al., Tetrathiomolybdate Partially Alleviates Erectile Dysfunction of Type 1 Diabetic Rats Through Affecting Ceruloplasmin/eNOS and Inhibiting Corporal Fibrosis and Systemic Inflammation. Sex Med 2021;XX:XXXXXX.
format article
author Yinghao Yin, MS
Jingxuan Peng, MS
Jun Zhou, MS
Hanfei Chen, MS
Dongyi Peng, PhD
Dongjie Li, PhD
Yu Gan, PhD
Guangming Yin, PhD
Yuxin Tang, PhD
author_facet Yinghao Yin, MS
Jingxuan Peng, MS
Jun Zhou, MS
Hanfei Chen, MS
Dongyi Peng, PhD
Dongjie Li, PhD
Yu Gan, PhD
Guangming Yin, PhD
Yuxin Tang, PhD
author_sort Yinghao Yin, MS
title Tetrathiomolybdate Partially Alleviates Erectile Dysfunction of Type 1 Diabetic Rats Through Affecting Ceruloplasmin/eNOS and Inhibiting Corporal Fibrosis and Systemic Inflammation
title_short Tetrathiomolybdate Partially Alleviates Erectile Dysfunction of Type 1 Diabetic Rats Through Affecting Ceruloplasmin/eNOS and Inhibiting Corporal Fibrosis and Systemic Inflammation
title_full Tetrathiomolybdate Partially Alleviates Erectile Dysfunction of Type 1 Diabetic Rats Through Affecting Ceruloplasmin/eNOS and Inhibiting Corporal Fibrosis and Systemic Inflammation
title_fullStr Tetrathiomolybdate Partially Alleviates Erectile Dysfunction of Type 1 Diabetic Rats Through Affecting Ceruloplasmin/eNOS and Inhibiting Corporal Fibrosis and Systemic Inflammation
title_full_unstemmed Tetrathiomolybdate Partially Alleviates Erectile Dysfunction of Type 1 Diabetic Rats Through Affecting Ceruloplasmin/eNOS and Inhibiting Corporal Fibrosis and Systemic Inflammation
title_sort tetrathiomolybdate partially alleviates erectile dysfunction of type 1 diabetic rats through affecting ceruloplasmin/enos and inhibiting corporal fibrosis and systemic inflammation
publisher Elsevier
publishDate 2022
url https://doaj.org/article/288fc032c5c945c9aee31c19a0d4e9af
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