The potential role of advanced glycation end product and iNOS in chronic renal failure-related testicular dysfunction. An experimental study.
OBJECTIVE
To investigate the impact of advanced glycation end products (AGEs) and inducible nitric oxide synthase (iNOS) in chronic renal failure (CRF)-associated testicular dysfunction in an experimental model. In additionally, we examined whether different peritoneal dialysis (PD) fluids could contribute to the elevation in AGE level and iNOS expression in the testes.


METHODS
Adult male Wistar rats, 10 and 12 weeks of age and weighing 200-330 g, were divided into 5 groups. Group 1 served as the control group. In group 2, CRF was induced and a peritoneal catheter was implanted, but the dialysis procedure was not performed until the end of the study. In group 3, CRF was induced and PD was performed with dialysis fluids containing 1.36% glucose and icodextrin. In group 4, CRF rats received dialysis fluids containing 3.86% glucose and icodextrin. Finally, an indwelling catheter was implanted and the dialysis procedure was performed using dialysis fluids containing 3.86% glucose and icodextrin (group 5). Chronic PD began 4 weeks after insertion of the catheter. Each morning, this fluid was drained and 20 ml dialysis fluid, containing either 1.36 or 3.86% glucose, was given intraperitoneally for 4 h in unanesthetized animals. Each evening, 20 ml icodextrin was given for 10 h. The dialysis procedure was performed for 8 weeks. The AGE level was determined from the 5-hydroxymethyl-2-furaldehyde (5-HMF) content of penis samples and iNOS expression was assessed by immunohistochemistry.


RESULTS
The elevation of 5-HMF was significant in the testes from groups 2, 3, 4, and 5 when compared with group 1. Furthermore, the differences between groups 2 and 4, 3 and 4, and 4 and 5 were also significant (p < 0.05). Immunohistochemical analysis revealed the presence of iNOS predominantly in the Leydig cells. While iNOS staining was significantly lower in group 1 than in other groups, there were also significant differences between groups 2 and 3, 2 and 4, 2 and 5, 3 and 5, and 4 and 5 (p < 0.05). Finally, a significant statistical correlation was found between the 5-HMF and iNOS levels (r = 0.698, p = 0.001).


CONCLUSIONS
The present study identifies, for the first time, a potential role of AGE and iNOS in experimental CRF-associated testicular dysfunction. In addition, we found that PD fluids containing glucose contribute to this effect. These results may lead to a better understanding of the pathophysiological pathway in CRF-related testicular dysfunction.
Köksal
Ismail Türker
IT
Department of Urology, Akdeniz University, Faculty of Medicine, Antalya, Turkey. koksal@med.akdeniz.edu.tr
Usta
Mustafa Faruk
MF
Akkoyunlu
Gökhan
G
Toptaş
Behiye
B
Gülkesen
Kemal Hakan
KH
Erdogru
Tibet
T
Tuncer
Murat
M
Baykal
Asli
A
Ersoy
Fevzi
F
Demir
Ramazan
R
Baykara
Mehmet
M
D000818:Animals; D005662:Furaldehyde / Q000031:analogs & derivatives* / Q000378:metabolism*; D007124:Immunoenzyme Techniques; D007676:Kidney Failure, Chronic; D008297:Male; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D010530:Peritoneal Dialysis; D051381:Rats; D017208:Rats, Wistar; D018709:Statistics, Nonparametric; D013737:Testis / Q000378:metabolism* / Q000473:pathology
D005662:Furaldehyde; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat