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AGE-Breaker ALT-711 Plus Insulin Could Restore Erectile Function in Streptozocin-Induced Type 1 Diabetic Rats.
J Sex Med. 2014 Jun;11(6):1452-62. doi: 10.1111/jsm.12533
Wang L, Tian W, Uwais Z, Li G, Li H, Guan R, Gao Z, Xin Z
Abstract:
.....ALT-711, an AGE cross-link breaker, has the therapeutic potential for ED but has been less intensively investigated. The aim of this study was to investigate the effects of an AGEs breaker 3-phenacyl-4,5-dimethylthiazolium chloride (ALT-711) plus insulin on erectile function in streptozocin (STZ)-induced type 1 diabetic rats. Fifty 8-week-old Sprague-Dawley rats were randomly distributed into five groups: normal control (C), diabetic (D), insulin-treated diabetic (D + I), ALT-711-treated diabetic (D + ALT-711) and insulin plus ALT-711-treated diabetic (D + I + ALT-711) rats. Diabetes was induced by a single intraperitoneal injection of STZ. Eight weeks after induction of diabetes, ALT-711 was administered by intraperitoneal injection. Two to six units of intermediate-acting insulin were utilized to achieve normal levels of glycemic control. After treatment for 6 weeks, erectile function was determined via measurement of intracavernous pressures (ICPs) following electrostimulation of the cavernous nerve. The deposition of AGEs, expression of RAGEs, superoxide dismutase activity, and lipid peroxidation were measured. We also evaluated penile histological changes such as smooth muscle contents, endothelial cells contents, and apoptotic activity. The main outcome measures were the ratio of ICP/mean arterial pressure (MAP), penile endothelial cells, smooth muscle cells, neuronal nitric oxide synthase, AGE and RAGE expression, malondialdehyde concentration, SOD activity, and apoptosis index.
Diabetic rats demonstrated significantly reduced ICP/MAP ratio, penile endothelial cells, smooth muscles cells, increased AGEs and RAGE expression, and increased apoptosis. Insulin and ALT-711 monotherapy partially restored erectile function and histological changes. However, the combination therapy group showed erectile parameters and components similar to those in C. ALT-711-treated group demonstrated less deposition of AGEs and lower expression of RAGE than those in insulin-treated group
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Diabetic rats demonstrated significantly reduced ICP/MAP ratio, penile endothelial cells, smooth muscles cells, increased AGEs and RAGE expression, and increased apoptosis. Insulin and ALT-711 monotherapy partially restored erectile function and histological changes. However, the combination therapy group showed erectile parameters and components similar to those in C. ALT-711-treated group demonstrated less deposition of AGEs and lower expression of RAGE than those in insulin-treated group
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PMID: 24766706
Tags: AGEs, ALT-711, erectile dysfunction, rats