Abstract
Background/aimCyclosporine 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 of rabbits undergoing renal pelvic perfusion.Materials and methodsA 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 4 groups (S1, S1’, S2, and S2’), consisting of 6 rabbits each. Groups S1 and S1’ were perfused with 20 mmHg of fluid, while groups S2 and S2’ were perfused with 60 mmHg of fluid. Administration to groups S1’ and S2’ was done intravenously, with CsA once a day for 1 week before 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 ultrastructure and 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.ResultsIt 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 experimental groups (S1 and S2). Furthermore, there was no difference between drug intervention groups S1’ and S2’.ConclusionThese results suggest that CsA can attenuate renal damage from severe hydronephrosis induced by renal pelvic perfusion in rabbits. It plays a protective role in the acute kidney injury process, possibly through increased MMP and mitochondrial changes.
Highlights
With the development of minimally invasive technology, many types of ureteroscopy and percutaneous nephroscope lithotripsy have become routine procedures in surgical intervention for kidney stones, as they have several advantages, including reduced postsurgical pain, efficient stone clearance, shorter hospitalization time, and reduced scar formation than open surgery [1,2]
It was found that the renal histopathological damage was ameliorated, mitochondrial vacuolization was lower, membrane potential (MMP) was higher, and the cytochrome C (CytC) and neutrophil gelatinase-associated lipocalin (NGAL) contents were decreased after drug intervention when compared to the experimental groups (S1 and S2)
There was no difference between drug intervention groups S1’ and S2’. These results suggest that Cyclosporine A (CsA) can attenuate renal damage from severe hydronephrosis induced by renal pelvic perfusion in rabbits
Summary
With the development of minimally invasive technology, many types of ureteroscopy and percutaneous nephroscope lithotripsy have become routine procedures in surgical intervention for kidney stones, as they have several advantages, including reduced postsurgical pain, efficient stone clearance, shorter hospitalization time, and reduced scar formation than open surgery [1,2]. Endourological operations need sufficient fluid perfusion to clearly flush out kidney stone fragments during these procedures, due to the limitations of the orifices [3]. These procedures can cause high intrapelvic pressure and pyelovenous backflow when the pressure increases to a certain extent, which could reduce renal arterial perfusion and lead to renal ischemic injury [4,5]. CsA has been thought to prevent mitochondrial permeability transition pore (mPTP) opening and attenuate cell apoptosis by exerting cardioprotective effects in a reperfusion injury model [8].
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