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TNF-α, Erectile Dysfunction, and NADPH Oxidase-Mediated ROS Generation in Corpus Cavernosum in High-Fat Diet/Streptozotocin-Induced Diabetic Rats.
MedLine Citation:
PMID:  22524530     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Introduction.  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. Aim.  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. Main Outcome Measures.  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. Long T, Liu G, Wang Y, Chen Y, Zhang Y, and Qin D. TNF-α, erectile dysfunction, and NADPH oxidase-mediated ROS generation in corpus cavernosum in high-fat diet/streptozotocin-induced diabetic rats. J Sex Med **;**:**-**.
Authors:
Ting Long; Guihua Liu; Yong Wang; Yuanbin Chen; Yuanyuan Zhang; Danian Qin
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-4-23
Journal Detail:
Title:  The journal of sexual medicine     Volume:  -     ISSN:  1743-6109     ISO Abbreviation:  -     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-4-24     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101230693     Medline TA:  J Sex Med     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© 2012 International Society for Sexual Medicine.
Affiliation:
Department of Physiology, Shantou University Medical College, Shantou, China Wake Forest Institute for Regenerative Medicine, Wake Forest University Health Sciences, Winston-Salem, NC, USA.
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