Husnu Alper BAGRİYANİK, Servet KİZİLDAG, Serap CİLAKER MİCİLİ, Mukaddes GUMUSTEKİN, Yasar Aysun MANİSALİGİL, Aslı CELİK

Assessment of Rac1 and β-PAK Expressions in a Mouse Model for Contrast-Induced Nephropathy

Purpose: Radiocontrast-induced nephropathy is an important clinical problem in high-risk patients. The mechanism of cytotoxic effect of radiocontrast media on kidneys is still not fully clarified. Rac1/β-PAK pathway has been shown to play a role in other nephropathies such as diabetic nephropathy. In this study, it was aimed to determine whether Rac1/β-PAK signalling pathway has any role in the development of contrast-induced nephropathy (CIN). Methods: Adult male Balb/C mice were used. A single dose of iohexol was given intraperitoneally. Thirty-two mice were divided into 5 groups including control (Group1, n=4), pretreatment (Group 2, n=7), low dose (2 g iodine/kg) iohexol (Group 3, n=7), medium dose (2.5 g iodine/kg) iohexol (Group 4, n=7) and high dose (3 g iodine/kg) iohexol (Group 5, n=7). The animals were sacrificed 24 hours after iohexol administration. Nephropathy were evaluated by histological and biochemical analysis methods. Expressions of Rac1 and β-PAK were evaluated by immunohistochemical method. Apoptosis was assessed by TUNEL method. Results: It was found that severity of nephropathy, apoptosis and β-PAK expressions significantly increased as iohexol dosage increased. Although Rac1 expression was higher in the iohexol group in comparison to the control and pretreatment groups, its increase did not show a dose-dependent manner. There was no significant difference among the groups in terms of serum creatinine. Serum cystatin C were increased in all groups compared to the control group, but significant increase was observed only in the pretreatment group. Conclusions: Our findings suggest that the Rac1/β-PAK signal transduction pathway may have a role in the contrast-induced nephropathy model.

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