title: Apocynin improves erectile function in diabetic rats through regulation of NADPH oxidase expression.
abstract: BACKGROUND
  Diabetes is a risk factor for erectile dysfunction (ED). The proposed mechanisms responsible for diabetic ED are associated with an increase in reactive oxygen species (ROS) production, overactivity of RhoA/ROCK signaling pathway and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, as seen in experimental models of diabetic rats.
  
  
  OBJECTIVE
  The aim of this study was to investigate whether NADPH oxidase inhibitor apocynin can ameliorate Streptozotocin (STZ)-induced diabetes-related ED by reducing the ROS production and inhibiting the activity of RhoA/ROCK signaling pathway.
  
  
  METHODS
  The diabetic rats were treated with and without the NADPH oxidase inhibitor apocynin.
  
  
  METHODS
  Erectile responses were evaluated by determining mean arterial blood pressure (MAP) and intracavernosal pressure (ICP) with electrical stimulation of the cavernous nerve. Levels of mRNA expression were measured by real-time polymerase chain reaction (RT-PCR). Levels of protein expression were examined by Western Blot. ROS production was measured by dihydroethidium (DHE) staining and thiobarbituric acid reactive substances assay.
  
  
  RESULTS
  The ratio of Maximum ICP-to-MAP (MaxICP/MAP) was significantly decreased in diabetic ED rats, compared to that of age-matched control rats (P < 0.05). Apocynin improved erectile function of diabetic rats (P < 0.05). Expression levels of RhoA (cytosol), nNOS and eNOS were reduced, compared to those of control rats (P < 0.05). Apocynin significantly elevated their expression levels in diabetic rats (P < 0.05). Expression levels of ROCK1, RhoA (membrane fraction), p-MYPT1 and NADPH oxidase subunits p47(phox) and p67(phox) were increased in diabetic rats when compared to those of control rats (P < 0.05), and it was observed that apocynin significantly reduced their expression levels in diabetic rats (P < 0.05). ROS production was increased in diabetic rats when compared to that of control rats (P < 0.05), the effect of apocynin was a reduction in the ROS production in diabetic rats (P < 0.05).
  
  
  CONCLUSIONS
  NADPH oxidase inhibitor apocynin can ameliorate diabetes-related ED by reducing the ROS production and inhibiting the activity of RhoA/ROCK signaling pathway.
authors.affiliation: Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Mingchao
authors.initials: M
authors.lastname: Li
authors.forename: Li
authors.initials: L
authors.lastname: Zhuan
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.forename: Ke
authors.initials: K
authors.lastname: Rao
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
authors.forename: Weihe
authors.initials: W
authors.lastname: Quan
authors.forename: Jihong
authors.initials: J
authors.lastname: Liu
authors.forename: Zhangqun
authors.initials: Z
authors.lastname: Ye
mesh_terms: D000098:Acetophenones / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure; D003921:Diabetes Mellitus, Experimental; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D008297:Male; D019255:NADPH Oxidases / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I / Q000235:genetics / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism; D010410:Penile Erection / Q000187:drug effects*; D010413:Penis / Q000294:innervation / Q000378:metabolism; D054645:Protein Phosphatase 1 / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D054460:rho-Associated Kinases / Q000235:genetics / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D000098:Acetophenones; D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D017392:Thiobarbituric Acid Reactive Substances; C056165:acetovanillone; D052248:Nitric Oxide Synthase Type I; D052250:Nitric Oxide Synthase Type III; D019255:NADPH Oxidases; D054460:rho-Associated Kinases; C499850:Ppp1r12a protein, rat; D054645:Protein Phosphatase 1; D020742:rhoA GTP-Binding Protein