TNF-α, Erectile Dysfunction, and NADPH Oxidase-Mediated ROS Generation in Corpus Cavernosum in High-Fat Diet/Streptozotocin-Induced Diabetic Rats
Article first published online: 23 APR 2012
© 2012 International Society for Sexual Medicine
The Journal of Sexual Medicine
Volume 9, Issue 7, pages 1801–1814, July 2012
How to Cite
Long, T., Liu, G., Wang, Y., Chen, Y., Zhang, Y. and Qin, D. (2012), TNF-α, Erectile Dysfunction, and NADPH Oxidase-Mediated ROS Generation in Corpus Cavernosum in High-Fat Diet/Streptozotocin-Induced Diabetic Rats. Journal of Sexual Medicine, 9: 1801–1814. doi: 10.1111/j.1743-6109.2012.02739.x
- Issue published online: 3 JUL 2012
- Article first published online: 23 APR 2012
- Erectile Dysfunction;
- Reactive Oxygen Species;
- Corpus Cavernosum;
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, p47phox and gp91phox expression compared with nondiabetic controls. INF neutralized TNF-α and significantly reduced ED in diabetic rats, in which marked decreases in p47phox and gp91phox 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 2012;9:1818–1831.