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Chemoprotective effect of a nuclear factor-kappaB inhibitor, pyrrolidine dithiocarbamate, against cisplatin-induced testicular damage in rats.
J Androl. 2009 Sep-Oct; 30(5):505-14.JA

Abstract

The objective of this study was to evaluate inducible nitric oxide synthase (iNOS) and nuclear factor-kappaB inhibitor (NF-kappaB) expression and the potential chemoprotective effects of an NF-kappaB inhibitor, pyrrolidine dithiocarbamate (PDTC), against cisplatin-induced testicular damage in rats. Rats were divided into 4 equal groups: group 1, control; group 2, injected with cisplatin (CIS) for 5 days (7 mg/kg/day intraperitoneally [IP]); group 3, injected with PDTC alone; group 4, injected with CIS plus PDTC (100 mg/kg IP). Body and testicular weights, plasma testosterone levels, and histopathologic structure of the testicular tissue were determined. The iNOS and NF-kappaB activity were evaluated immunohistochemically by staining p65 to define NF-kappaB 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 weights, plasma testosterone levels, activity of GSH-Px, and GSH levels were all significantly decreased, whereas the levels of MDA and NO were significantly increased in rats of the CIS group. PDTC treatment increased plasma testosterone levels. A significant increase in GSH levels and GSH-Px activity and a decrease in MDA and NO levels in testicular tissue were observed in the CIS + PDTC group. Immunohistochemically, there was a marked staining for iNOS and NF-kappaB/p65 expression in rats injected with CIS compared with the control (P < .001). CIS caused irregular seminiferous tubules, reduction of seminiferous epithelial layers, significant arrest of maturation, and perivascular fibrosis. Moreover, PDTC administration to CIS-treated rats significantly prevented these histopathologic chances, as well. CIS induces iNOS expression through activation of NF-kappaB/p65, and CIS-induced testicular toxicity may be prevented by PDTC, which is a selective NF-kappaB inhibitor.

Authors+Show Affiliations

Department of Urology, Bezm-i Alem Valide Sultan Vakif Gureba Research and Education Hospital, Istanbul, Turkey. ozlemyusufilbey@hotmail.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

19234314

Citation

Ilbey, Yusuf Ozlem, et al. "Chemoprotective Effect of a Nuclear factor-kappaB Inhibitor, Pyrrolidine Dithiocarbamate, Against Cisplatin-induced Testicular Damage in Rats." Journal of Andrology, vol. 30, no. 5, 2009, pp. 505-14.
Ilbey YO, Ozbek E, Simsek A, et al. Chemoprotective effect of a nuclear factor-kappaB inhibitor, pyrrolidine dithiocarbamate, against cisplatin-induced testicular damage in rats. J Androl. 2009;30(5):505-14.
Ilbey, Y. O., Ozbek, E., Simsek, A., Cekmen, M., Otunctemur, A., & Somay, A. (2009). Chemoprotective effect of a nuclear factor-kappaB inhibitor, pyrrolidine dithiocarbamate, against cisplatin-induced testicular damage in rats. Journal of Andrology, 30(5), 505-14. https://doi.org/10.2164/jandrol.108.006270
Ilbey YO, et al. Chemoprotective Effect of a Nuclear factor-kappaB Inhibitor, Pyrrolidine Dithiocarbamate, Against Cisplatin-induced Testicular Damage in Rats. J Androl. 2009 Sep-Oct;30(5):505-14. PubMed PMID: 19234314.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Chemoprotective effect of a nuclear factor-kappaB inhibitor, pyrrolidine dithiocarbamate, against cisplatin-induced testicular damage in rats. AU - Ilbey,Yusuf Ozlem, AU - Ozbek,Emin, AU - Simsek,Abdulmuttalip, AU - Cekmen,Mustafa, AU - Otunctemur,Alper, AU - Somay,Adnan, Y1 - 2009/02/19/ PY - 2009/2/24/entrez PY - 2009/2/24/pubmed PY - 2009/10/27/medline SP - 505 EP - 14 JF - Journal of andrology JO - J Androl VL - 30 IS - 5 N2 - The objective of this study was to evaluate inducible nitric oxide synthase (iNOS) and nuclear factor-kappaB inhibitor (NF-kappaB) expression and the potential chemoprotective effects of an NF-kappaB inhibitor, pyrrolidine dithiocarbamate (PDTC), against cisplatin-induced testicular damage in rats. Rats were divided into 4 equal groups: group 1, control; group 2, injected with cisplatin (CIS) for 5 days (7 mg/kg/day intraperitoneally [IP]); group 3, injected with PDTC alone; group 4, injected with CIS plus PDTC (100 mg/kg IP). Body and testicular weights, plasma testosterone levels, and histopathologic structure of the testicular tissue were determined. The iNOS and NF-kappaB activity were evaluated immunohistochemically by staining p65 to define NF-kappaB 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 weights, plasma testosterone levels, activity of GSH-Px, and GSH levels were all significantly decreased, whereas the levels of MDA and NO were significantly increased in rats of the CIS group. PDTC treatment increased plasma testosterone levels. A significant increase in GSH levels and GSH-Px activity and a decrease in MDA and NO levels in testicular tissue were observed in the CIS + PDTC group. Immunohistochemically, there was a marked staining for iNOS and NF-kappaB/p65 expression in rats injected with CIS compared with the control (P < .001). CIS caused irregular seminiferous tubules, reduction of seminiferous epithelial layers, significant arrest of maturation, and perivascular fibrosis. Moreover, PDTC administration to CIS-treated rats significantly prevented these histopathologic chances, as well. CIS induces iNOS expression through activation of NF-kappaB/p65, and CIS-induced testicular toxicity may be prevented by PDTC, which is a selective NF-kappaB inhibitor. SN - 1939-4640 UR - https://www.unboundmedicine.com/medline/citation/19234314/Chemoprotective_effect_of_a_nuclear_factor_kappaB_inhibitor_pyrrolidine_dithiocarbamate_against_cisplatin_induced_testicular_damage_in_rats_ DB - PRIME DP - Unbound Medicine ER -