Upregulated NADPH oxidase contributes to diabetic testicular complication and is relieved by strontium fructose 1,6-diphosphate.
Diabetes is frequently associated with declining sexual function resulting from oxidative damage. NADPH oxidase is a major resource of reactive oxygen species (ROS) in the testes and is likely related to an activated endothelin-1 (ET-1) system. An activation of NADPH oxidase-ET-1 pathway was hypothesized in diabetic testopathy. We verified the hypothesis and tested if strontium fructose 1,6-diphosphate (FDP-Sr) could relieve these changes in diabetic testis as compared to testosterone propionate (TP) and sildenafil. Diabetes was produced in male Sprague-Dawley rats 8 weeks after a single injection of streptozotocin (STZ), and interventions with testosterone propionate (TP), sildenafil and FDP-Sr were conducted in the last 4 weeks. Blood glucose, testosterone, follicle stimulating hormone (FSH) , luteinizing hormone (LH) and expressions of NADPH oxidase subunits and the ET system were measured. Decreased insulin, FSH, LH and testosterone in serum were found associating with testicular oxidative stress in STZ-injected rats. Additionally, over-expressions of NADPH oxidase p22, p47, p67 subunits and the ET pathway were significant in the diabetic testis relative to normal and were completely abolished by FDP-Sr. Both TP and sildenafil were not beneficial to diabetic testopathy except serum androgen raised by TP. Activated NADPH oxidase and ET system are significant contributing to testis injury and are responded to FDP-Sr only, against both TP and sildenafil, by restoring the testis function and the hypothalamus-pituitary-testis axis. It is due to its extra-energy supply and an antioxidant activity of FDP-Sr.
Xu
M
M
Research Division of Pharmacology, China Pharmaceutical University, Nanjing, China.
Dai
D Z
DZ
Zhang
Q
Q
Cheng
Y S
YS
Dai
Y
Y
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000150:complications*; D019332:Endothelin-1 / Q000032:analysis; D005640:Follicle Stimulating Hormone / Q000097:blood; D005635:Fructosediphosphates / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D019255:NADPH Oxidases / Q000096:biosynthesis*; D018384:Oxidative Stress / Q000187:drug effects; D010879:Piperazines / Q000627:therapeutic use; D011687:Purines / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000627:therapeutic use; D013733:Testicular Diseases / Q000188:drug therapy* / Q000201:enzymology*; D013737:Testis / Q000201:enzymology / Q000503:physiopathology; D013739:Testosterone / Q000097:blood; D043343:Testosterone Propionate / Q000627:therapeutic use
D019332:Endothelin-1; D005635:Fructosediphosphates; D007328:Insulin; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D013739:Testosterone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D000068677:Sildenafil Citrate; D019255:NADPH Oxidases; C029063:fructose-1,6-diphosphate; D043343:Testosterone Propionate