title: Argirein alleviates corpus cavernosum dysfunction by suppressing pro-inflammatory factors p66Shc and ER stress chaperone Bip in diabetic rats.
abstract: OBJECTIVE
  The aim was to investigate whether argirein, which releases rhein and L-arginine after medication, could improve erectile dysfunction (ED) in diabetic rats through normalising the abnormalities of nitric oxide synthase (NOS), p66Shc and immunoglobulin heavy-chain binding protein (Bip), in the corpus cavernosum (CC).
  
  
  METHODS
  SD rats were randomly divided into six groups. Except for the control group, rats were injected with streptozotocin (STZ) (60 mg/kg, i.p.) once. During weeks 5-8 following STZ injection, except for STZ-injected untreated rats, others were treated with aminoguanidine (AMG; 100 mg/kg/day, i.g.), or argirein at three doses (50, 100 and 200 mg/kg/day, i.g.). The vascular activity and biomarkers of the cavernosum were examined.
  
  
  RESULTS
  Constrictive and dilative activity was abnormal in the CC, associated with decreased nitric oxide (NO) in serum in the diabetic (DM) group. Increased expression of p66Shc, Bip and inducible nitric oxide synthase (iNOS) and decreased endothelial nitric oxide synthase (eNOS) in the CC were significant in DM rats. Argirein and AMG improved these abnormities significantly.
  
  
  CONCLUSIONS
  We concluded that vascular activity of the cavernosal tissue was impaired due to upregulated p66Shc and Bip in the diabetic CC. Argirein alleviates the vascular dysfunction of the CC by suppressing these upregulated pro-inflammatory proteins caused by diabetic lesions.
authors.affiliation: China Pharmaceutical University, Nanjing, China.
authors.forename: Yu-Si
authors.initials: YS
authors.lastname: Cheng
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Cong
authors.forename: De-Zai
authors.initials: DZ
authors.lastname: Dai
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yin
authors.initials: Y
authors.lastname: Dai
mesh_terms: D000818:Animals; D000880:Anthraquinones / Q000008:administration & dosage / Q000627:therapeutic use*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000627:therapeutic use*; D001120:Arginine / Q000008:administration & dosage / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D003925:Diabetic Angiopathies / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D007172:Erectile Dysfunction / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D005786:Gene Expression Regulation / Q000187:drug effects; D006146:Guanidines / Q000627:therapeutic use; D006360:Heat-Shock Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D008297:Male; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D010413:Penis / Q000098:blood supply / Q000187:drug effects / Q000503:physiopathology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D055765:Shc Signaling Adaptor Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects; D000091342:Endoplasmic Reticulum Chaperone BiP
chemical_list: D000880:Anthraquinones; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001120:Arginine; D015415:Biomarkers; D004338:Drug Combinations; D004791:Enzyme Inhibitors; D006146:Guanidines; D006360:Heat-Shock Proteins; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D055765:Shc Signaling Adaptor Proteins; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; C051684:GRP78 protein, rat; D000091342:Endoplasmic Reticulum Chaperone BiP; C528035:Shc1 protein, rat; C576350:argirein; C496318:Nos2 protein, rat; C496316:Nos3 protein, rat; C004479:pimagedine