title: Probucol Improves Erectile Function by Restoring Endothelial Function and Preventing Cavernous Fibrosis in Streptozotocin-induced Diabetic Rats.
abstract: OBJECTIVE
  To investigate the effects of probucol on erectile function in streptozotocin-induced diabetic rats and explore the underlying mechanisms.
  
  
  METHODS
  A total of thirty 12-week-old Sprague-Dawley male rats received a 1-time intraperitoneal streptozotocin (60 mg/kg) or vehicle injection after a 12-hour fast. Three days later, the streptozotocin-induced diabetic rats were randomly divided into 2 groups and were treated with daily gavage feedings of probucol at doses of 0 and 500 mg/kg for 12 weeks. A positive control group underwent intraperitoneal injection of saline followed by daily gavage of saline solution. Erectile function was assessed by electrical stimulation of the cavernous nerves with real-time intracavernous pressure measurement. After euthanasia, penile tissue was investigated using immunohistochemistry, Western blot, and ELISA to assess the protein arginine-N-methyltransferase 1/dimethylarginine dimethylaminohydrolase/asymmetric dimethylarginine/nitric oxide synthase metabolism pathway. Superoxide dismutase activity and malondialdehyde levels were detected by colorimetry. We also evaluated penile histological changes such as smooth muscle contents and Masson's trichrome stain.
  
  
  RESULTS
  Significant recovery of erectile function was observed in the probucol-treated rats than the untreated diabetic rats. The protein expression of dimethylarginine dimethylaminohydrolase and nitric oxide synthase, cyclic guanosine monophosphate concentrations, and superoxide dismutase activity in cavernous tissue of probucol-treated rats were significantly higher than the untreated diabetic rats. The protein expression of protein arginine-N-methyltransferase 1, asymmetric dimethylarginine concentrations, and malondialdehyde levels in cavernous tissue of probucol-treated rats were significantly lower than the untreated diabetic rats. In addition, probucol treatment markedly augments the cavernous smooth muscle content.
  
  
  CONCLUSIONS
  Probucol treatment improves erectile function by restoring endothelial function and preventing cavernous fibrosis in streptozotocin-induced diabetic rats.
authors.affiliation: Department of Urology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China.
authors.forename: Ke-Qin
authors.initials: KQ
authors.lastname: Zhang
authors.affiliation: Department of Urology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Chen
authors.affiliation: Department of Urology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China.
authors.forename: Ding-Qi
authors.initials: DQ
authors.lastname: Sun
authors.affiliation: Department of Urology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Urology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Li
authors.affiliation: Department of Urology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China. Electronic address: qiangfu68@163.com.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Fu
mesh_terms: D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D003921:Diabetes Mellitus, Experimental / Q000150:complications; D004727:Endothelium / Q000187:drug effects / Q000502:physiology; D007172:Erectile Dysfunction / Q000188:drug therapy* / Q000209:etiology; D005355:Fibrosis / Q000517:prevention & control; D008297:Male; D010410:Penile Erection / Q000187:drug effects; D010413:Penis / Q000473:pathology*; D011341:Probucol / Q000494:pharmacology / Q000627:therapeutic use*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D013311:Streptozocin / Q000008:administration & dosage
chemical_list: D000924:Anticholesteremic Agents; D013311:Streptozocin; D011341:Probucol