BACKGROUND/AIMS: Cyclosporine (CsA)-induced renal injury causes renal tubular acidosis. The current study was performed to evaluate the influence of CsA-induced renal injury on the ammonia transporter family members, Rh B-glycoprotein (Rhbg) and Rh C-glycoprotein (Rhcg). METHODS: Rats were treated daily for 1 or 4 weeks with vehicle (VH) or CsA. Induction of chronic CsA-induced nephropathy was confirmed by demonstrating impaired renal function and characteristic histopathology. Rhbg and Rhcg expression was evaluated with immunoblot, immunohistochemistry, real-time RT-PCR and electron microscopy. RESULTS: CsA treatment for 4 weeks developed mild metabolic acidosis and decreased urinary ammonia excretion. Rhcg mRNA expression was unchanged in both the cortex and outer medulla, but Rhcg protein expression in the CsA group was significantly reduced in the cortex and outer medulla. There were no significant differences in Rhbg mRNA and protein expression between the CsA and VH group. CONCLUSION: Long-term treatment with CsA in rats results in decreased urinary ammonia excretion accompanied by decreased expression of Rhcg; these changes are likely to mediate the CsA-induced defect in ammonium excretion in the collecting duct. (c) 2008 S. Karger AG, Basel.
BACKGROUND/AIMS: Cyclosporine (CsA)-induced renal injury causes renal tubular acidosis. The current study was performed to evaluate the influence of CsA-induced renal injury on the ammonia transporter family members, Rh B-glycoprotein (Rhbg) and Rh C-glycoprotein (Rhcg). METHODS:Rats were treated daily for 1 or 4 weeks with vehicle (VH) or CsA. Induction of chronic CsA-induced nephropathy was confirmed by demonstrating impaired renal function and characteristic histopathology. Rhbg and Rhcg expression was evaluated with immunoblot, immunohistochemistry, real-time RT-PCR and electron microscopy. RESULTS:CsA treatment for 4 weeks developed mild metabolic acidosis and decreased urinary ammonia excretion. Rhcg mRNA expression was unchanged in both the cortex and outer medulla, but Rhcg protein expression in the CsA group was significantly reduced in the cortex and outer medulla. There were no significant differences in Rhbg mRNA and protein expression between the CsA and VH group. CONCLUSION: Long-term treatment with CsA in rats results in decreased urinary ammonia excretion accompanied by decreased expression of Rhcg; these changes are likely to mediate the CsA-induced defect in ammonium excretion in the collecting duct. (c) 2008 S. Karger AG, Basel.
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