Repaglinide inhibits cyclosporine A-induced renal tubular toxicity by affecting apoptosis and Bax and Bcl-2 expression

Authors: Jin LI, Hui LI, QI XIONG LI, Ying XUE

Abstract: Background/aim: Repaglinide (RG) is a prandial glucose regulator used for the treatment of type 2 diabetes. Our recent study showed that RG plays an important role in cyclosporine A (CsA)-induced nephrotoxicity through its antioxidant properties. However, it is not known whether or not RG has any protective effect on CsA-induced renal tubular toxicity by affecting apoptosis and expression of apoptosis-associated protein. The purpose of this study was to investigate the effects of RG on CsA-induced renal tubule apoptosis and Bax and Bcl-2 protein expression in rats. Materials and methods: Forty male Sprague Dawley rats weighing 250-300 g were randomly divided into four groups: administrations of olive oil (control, per os (PO)), CsA (30 mg/kg in olive oil, subcutaneous (SC)), and RG (0.2 or 0.4 mg/kg, PO) plus CsA (30 mg/kg in olive oil, SC) every day for 15 days. Results: Our results showed that SC administration of CsA (30 mg/kg) to rats produced marked injury and apoptosis, elevation of Bax protein expression, and inhibition of Bcl-2 protein expression in the kidneys, which were reversed significantly by oral administration of RG (0.2 or 0.4 mg/kg). Conclusion: The findings of our study indicate that RG may play an important role in protecting the kidneys through inhibiting apoptosis, Bax, and Bcl-2 protein expression.

Keywords: Repaglinide, cyclosporine A, apoptosis, Bax and Bcl-2 expression, renal, rat

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