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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Oxford University Press
2022-02-01
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| Series: | Sexual Medicine |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2050116121001355 |
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| 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 |
| collection | DOAJ |
| 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 2022;10:100455. |
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| institution | Directory Open Access Journal |
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| spelling | doaj.art-288fc032c5c945c9aee31c19a0d4e9af2023-09-02T18:23:34ZengOxford University PressSexual Medicine2050-11612022-02-01101100455Tetrathiomolybdate Partially Alleviates Erectile Dysfunction of Type 1 Diabetic Rats Through Affecting Ceruloplasmin/eNOS and Inhibiting Corporal Fibrosis and Systemic InflammationYinghao Yin, MS0Jingxuan Peng, MS1Jun Zhou, MS2Hanfei Chen, MS3Dongyi Peng, PhD4Dongjie Li, PhD5Yu Gan, PhD6Guangming Yin, PhD7Yuxin Tang, PhD8Department of Urology, The Third Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Urology, The Third Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Urology, The Third Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Urology, The Third Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Urology, The Third Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China; Institute of Clinical Pharmacology, Central South University; Hunan Key Laboratory of Pharmacogenetics, Changsha, China; Xiangya International Medical Center, Department of Geriatric Urology, Xiangya Hospital, Central South University, Changsha, China; National Clinical Research Center for Geriatric Disorders, Changsha, ChinaDepartment of Urology, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Urology, The Third Xiangya Hospital, Central South University, Changsha, China; Corresponding Author: Guangming Yin, PhD, Department of Urology, The Third Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Urology, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, China; Guangdong Provincial Key Laboratory of Biomedical Imaging, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, China; Corresponding Author: Yuxin Tang, PhD, Department of Urology, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, China, Guangdong Provincial Key Laboratory of Biomedical Imaging, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, ChinaIntroduction: 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 2022;10:100455.http://www.sciencedirect.com/science/article/pii/S2050116121001355TetrathiomolybdateDiabetes MellitusErectile DysfunctionCeruloplasmineNOS |
| spellingShingle | 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 Sexual Medicine Tetrathiomolybdate Diabetes Mellitus Erectile Dysfunction Ceruloplasmin eNOS |
| title | 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_short | 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 |
| topic | Tetrathiomolybdate Diabetes Mellitus Erectile Dysfunction Ceruloplasmin eNOS |
| url | http://www.sciencedirect.com/science/article/pii/S2050116121001355 |
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