Protective effect of curcumin in cisplatin-induced oxidative injury in rat testis: mitogen-activated protein kinase and nuclear factor-kappa B signaling pathways.
BACKGROUND
The aim of this study was to investigate the cellular/biochemical mechanisms by which cisplatin (CIS) causes testicular toxicity. We evaluated the role of inducible nitric oxide synthase (iNOS) expression, mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-kB) activation in the pathogenesis of testicular damage induced by CIS, and investigated the effects of curcumin (CMN) against CIS-induced testicular injury in rats.


METHODS
Rats were divided into five equal groups: (1) control, (2) CIS, (3) CMN, (4) CIS + CMN and (5) CIS + corn oil. After the treatment, body and testicular weights, and plasma testosterone levels were observed, along with the biochemical, histopathological and immunohistochemical changes in testes.


RESULTS
Testicular weight, plasma testosterone levels, activities of glutathione peroxidase (GSH-Px) and glutathione (GSH) levels significantly decreased, whereas the level of malondialdehyde (MDA) and nitric oxide (NO) significantly increased with CIS compared with the controls. A significant increase in plasma testosterone levels, GSH levels and GSH-Px activity, and a decrease in MDA and NO levels in testicular tissue were observed with CIS + CMN compared with that with CIS alone. There was marked staining for iNOS, MAPK/p38 and NF-kB/p65 expression with CIS compared with the control and CIS + CMN groups. CIS caused irregular seminiferous tubules, reduction of seminiferous epithelial layers, significant maturation arrest and perivascular fibrosis. CMN administration to CIS-treated rats significantly prevented these histopathologic changes.


CONCLUSIONS
MAPK and NF-kB activation have a significant role in CIS-induced testicular toxicity. CMN has a strong potential for use as a therapeutic adjuvant in CIS gonadotoxicity.
Ilbey
Yusuf Ozlem
YO
Department of Urology, Bezm-i Alem Valide Sultan Vakif Gureba Research and Education Hospital, Aksaray, Istanbul, Turkey. ozlemyusufilbey@hotmail.com
Ozbek
Emin
E
Cekmen
Mustafa
M
Simsek
Abdulmuttalip
A
Otunctemur
Alper
A
Somay
Adnan
A
D000818:Animals; D002945:Cisplatin / Q000494:pharmacology / Q000633:toxicity*; D003474:Curcumin / Q000494:pharmacology*; D007150:Immunohistochemistry / Q000379:methods; D020935:MAP Kinase Signaling System; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D013737:Testis / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D013739:Testosterone / Q000378:metabolism
D016328:NF-kappa B; D009569:Nitric Oxide; D013739:Testosterone; D003474:Curcumin; D002945:Cisplatin