Journal of Andrology Testis Workshop 2009
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Published-Ahead-of-Print February 19, 2009, DOI:10.2164/jandrol.108.006270

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Chemoprotective Effect of a Nuclear Factor-kB Inhibitor, Pyrrolidine Dithiocarbamate, Against Cisplatin-Induced Testicular Damage in Rats

Yusuf Ozlem Ilbey *, Emin Ozbek , Abdulmuttalip Simsek , Mustafa Cekmen , Alper Otunctemur , and Adnan Somay

* To whom correspondence should be addressed. E-mail: ozlemyusufilbey{at}hotmail.com.

Our objective was to evaluate the inducible nitric oxide synthase (iNOS) and NF-kB expression, and the potential chemoprotective effects of a nuclear factor-kB inhibitor (NF-kB), pyrrolidine dithiocarbamate (PDTC), against cisplatin-induced testicular damage in rats. Rats were divided into three equal groups; group 1, control; group 2, injected with cisplatin (CIS) for 5 days (7 mg/kg/day, intraperitoneally [i.p.]); group 3, injected with PDTC alone; group 4, injected with CIS plus PDTC (100 mg/kg, i.p.). Body and testicular weight, plasma testosterone level and histopathologic structure of the testicular tissue were determined. The iNOS and NF-kB activity were evaluated immunohistochemically by staining p65 to define NF-kB activity. Malondialdehyde (MDA), reduced glutathione (GSH) and nitric oxide (NO) levels, and glutathione peroxidase (GSH-Px) activity were assessed in testicular tissue. Body and testicular weight, plasma testosterone level, the activities of GSH-Px, and GSH levels were all significantly decreased, whereas the level of MDA and NO were significantly increased in rats of CIS group. PDTC treatment increased plasma testosterone level. A significant increase in GSH levels and GSP-Px activity, and a decrease of MDA and NO level in testicular tissue, were observed in CIS + PDTC group. Immunohistochemically, there was a marked staining for iNOS and NF-kB/p65 expression in rats injected with CIS compared with the control (p<0.001). CIS caused irregular seminifereous tubules, reduction seminiferous epithelial layers, significant arrest of maturation, and perivascular fibrosis. Moreover, PDTC significantly improved histopathologic chances, as well. Thus, CIS induces iNOS expression through activation of NF-kB/p65, and CIS-induced testicular toxicity may be prevented by PDTC which is a selective NF-kB inhibitor.


Key words: Testis • Pyrrolidine dithiocarbamate • cisplatin • oxidative stress • selective nuclear factor kB • testicular damage






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