Protective effect of cyclosporine A in the treatment of severe hydronephrosis in a rabbit renal pelvic perfusion model

Abstract

Background/aim: Cyclosporine A (CsA), a traditional immunosuppressive compound, has been reported to specifically prevent ischemia reperfusion tissue injury via apoptosis pathway. This study aimed to explore the renoprotective effects of CsA on the kidneys ofrabbits undergoing renal pelvic perfusion.Materials and methods: A total of 30 rabbits were randomly assigned into a control group (n = 6) and an experimental group (n = 24).The experimental group underwent a surgical procedure that induced severe hydronephrosis and was then stochastically divided into 4groups (S1, S1’, S2, and S2’), consisting of 6 rabbits each. Groups S1 and S1’ were perfused with 20 mmHg of fluid, while groups S2 andS2’ were perfused with 60 mmHg of fluid. Administration to groups S1’ and S2’ was done intravenously, with CsA once a day for 1 weekbefore perfusion. In the control group, after severe hydronephrosis was induced, a sham operation was performed in a second laparotomy. Acute kidney damage was evaluated using hematoxylin and eosin staining, in addition to analyzing the mitochondrial ultrastructureand mitochondrial membrane potential (MMP). The cytochrome C (CytC) and neutrophil gelatinase-associated lipocalin (NGAL)expression were examined immunohistochemically using Western blotting and reverse transcription-polymerase chain reaction.Results: It was found that the renal histopathological damage was ameliorated, mitochondrial vacuolization was lower, MMP was higher, and the CytC and NGAL contents were decreased after drug intervention (groups S1’ and S2’) when compared to the experimentalgroups (S1 and S2). Furthermore, there was no difference between drug intervention groups S1’ and S2’.Conclusion: These results suggest that CsA can attenuate renal damage from severe hydronephrosis induced by renal pelvic perfusionin rabbits. It plays a protective role in the acute kidney injury process, possibly through increased MMP and mitochondrial changes.