title: TNF-α, erectile dysfunction, and NADPH oxidase-mediated ROS generation in corpus cavernosum in high-fat diet/streptozotocin-induced diabetic rats.
abstract: BACKGROUND
  Patients with diabetes-associated erectile dysfunction (ED) are characterized by an increase in circulating tumor necrosis factor-alpha (TNF-α). However, no study has indicated whether and how TNF-α plays a role in the pathogenesis of ED associated with diabetes.
  
  
  OBJECTIVE
  We examined the effects and potential mechanism of infliximab (INF), a chimeric monoclonal antibody to TNF-α, on reactive oxygen species (ROS) generation in corpus cavernosum and ED in diabetic rats.
  
  
  METHODS
  Four groups of male rats were used: age-matched normal controls; diabetic rats induced by a high-fat diet (HFD) combined with a single streptozotocin (STZ) injection (35 mg/kg body weight, intraperitoneal [i.p.]); nondiabetic rats receiving INF (5 mg/kg body weight/week, i.p.), and diabetic rats receiving INF. Erectile function was assessed with electrical stimulation of the cavernous nerve after 8 weeks. The blood and penile tissues were harvested for plasma biochemical determinations, serum TNF-α measurement, penile ROS detection, and molecular assays of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits, endothelial nitric oxide synthase (eNOS), phospho-eNOS, and neural nitric oxide synthase (nNOS) in the penis.
  
  
  METHODS
  The effect of INF on HFD/STZ-induced diabetic ED and NADPH oxidase-mediated ROS generation was studied in diabetic corpus cavernosum.
  
  
  RESULTS
  Untreated diabetic rats displayed significantly decreased erectile parameters, and increased plasma TNF-α levels, penile ROS production, p47(phox) and gp91(phox) expression compared with nondiabetic controls. INF neutralized TNF-α and significantly reduced ED in diabetic rats, in which marked decreases in p47(phox) and gp91(phox) expression and ROS generation in corpus cavernosum were noted. The ratio of phospho-eNOS to eNOS and expression of nNOS in the penis were significantly increased in INF-treated vs. untreated diabetic rats.
  
  
  CONCLUSIONS
  Increased TNF-α expression associated with diabetes contributes to ED by promoting NAPDH oxidase-mediated ROS generation in corpus cavernosum. INF protects against diabetic ED by neutralizing TNF-α.
authors.affiliation: Department of Physiology, Shantou University Medical College, Shantou, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Long
authors.forename: Guihua
authors.initials: G
authors.lastname: Liu
authors.forename: Yong
authors.initials: Y
authors.lastname: Wang
authors.forename: Yuanbin
authors.initials: Y
authors.lastname: Chen
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Danian
authors.initials: D
authors.lastname: Qin
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015153:Blotting, Western; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*; D004041:Dietary Fats / Q000009:adverse effects*; D007172:Erectile Dysfunction / Q000209:etiology / Q000503:physiopathology*; D005455:Fluorescent Antibody Technique; D000069285:Infliximab; D008297:Male; D019255:NADPH Oxidases / Q000378:metabolism*; D010410:Penile Erection / Q000187:drug effects / Q000502:physiology; D010413:Penis / Q000737:chemistry / Q000378:metabolism / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000032:analysis*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis*
chemical_list: D000911:Antibodies, Monoclonal; D004041:Dietary Fats; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D019255:NADPH Oxidases