Beneficial effects of oltipraz, nuclear factor – erythroid – 2 – related factor 2 (Nrf2), on renal damage in unilateral ureteral obstruction rat model

Vol. 44 (6): 1243-1251, November – December, 2018

doi: 10.1590/S1677-5538.IBJU.2018.0232


ORIGINAL ARTICLE

Emre Can Polat 1, Huseyin Besiroglu 2, Levent Ozcan 3, Alper Otunctemur 1, Ahmet Tugrul Eruyar 4, Adnan Somay 5, Nurver Ozbay 5, Mustafa Cekmen 6, Ceyla Eraldemır 7, Emin Ozbek 8
1 Department of Urology, Okmeydani Training and Research Hospital, University of Health Sciences, Istanbul, Turkey; 2 Department of Urology, Catalca Ilyas Cokay State Hospital, Istanbul, Turkey; 3 Department of Urology, Derince Training and Research Hospital, University of Health Sciences, Kocaeli, Turkey; 4 Department of Pathology, Derince Training and Research Hospital, University of Health Sciences, Kocaeli, Turkey; 5 Department of Pathology, Fatih Sultan Mehmet Training and Research Hospital, University of Health Sciences, Istanbul, Turkey; 6 Department of Biochemistry, Istanbul Medeniyet University, Istanbul, Turkey; 7 Department of Biochemistry, Kocaeli University, Kocaeli, Turkey; 8 Department of Urology, Cerrahpasa Medical School, Istanbul University, Istanbul, Turkey

ABSTRACT

Introduction: We investigated whether Oltipraz (OPZ) attenuated renal fibrosis in a unilateral ureteral obstruction (UUO) rat model.

Materials and Methods: We randomly divided 32 rats into four groups, each consisting of eight animals as follows: Rats in group 1 underwent a sham operation and received no treatment. Rats in group 2 underwent a sham operation and received OPZ. Rats in group 3 underwent unilateral ureteral ligation and received no treatment. Group 4 rats were subjected to unilateral ureteral ligation plus OPZ administration. Transforming growth factor beta-1 (TGF-β1), E-cadherin, nitric oxide (NO) and hydroxyproline levels were measured. Histopathological and immunohistochemical examinations were carried out.

Results: TGF-β1, NO and E-cadherin levels in the UUO group were significantly higher than the sham group and these values were significantly different in treated groups compared to the UUO group. In rats treated with UUO + OPZ, despite the presence of mild tubular degeneration and less severe tubular necrosis, glomeruli maintained a better morphology when compared to the UUO group. Expressions of αSMA in immunohistochemistry showed that the staining positivity decreased in the tubules of the OPZ-treated group.

Conclusions: While the precise mechanism of action remains unknown, our results demonstrated that OPZ exerted a protective role in the UUO-mediated renal fibrosis rat model highlighting a promising therapeutic potency of Nrf2-activators for alleviating the detrimental effects of unilateral obstruction in kidneys.

 

Keywords: Oltipraz [Supplementary Concept]; Renal Insufficiency; Ureter

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