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

Abstract

Introduction 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]. However, minimally invasive surgery in the kidney may not be minimally invasive within the kidney itself. 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]. In addition, there is a certain degree of hy-dronephrosis in patients with upper urinary tract stones. A previous study demonstrated that a 60 mmHg renal pelvic perfusion substantially aggravated kidney damage in a rabbit model of hydronephrosis via mitochondrial injury [6]. Nevertheless, effective protection for hydronephrotic kidneys after renal pelvic perfusion has not yet been studied. Cyclosporine A (CsA), known as an immunosuppressive compound, has been traditionally used to prevent and treat transplant rejection [7]. Recently, CsA has been thought to specifically prevent mitochondrial permeability transition pore (mPTP) opening and attenuate cell apoptosis by exerting cardioprotective effects in a reperfusion injury model [8]. Moreover, previous studies have shown that CsA protects against tissue ischemia-reperfusion injury in the brain [9], lung [10], and kidney [11] in vivo. However, whether CsA affects renal pelvic perfusion-in-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 of rabbits 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 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 ...

Galectin‑1 alleviates myocardial ischemia‑reperfusion injury by reducing the inflammation and apoptosis of cardiomyocytes

“…IL-6 acts directly on cardiomyocytes to induce myocardial inhibition by altering the function of the sarcoplasmic reticulum and reducing the concentration of calcium ions in the cell cytoplasm (44). IL-6 has also been previously revealed to serve an important regulatory role in myocardial apoptosis in a rat model of MIRI (35). Therefore, the anti-inflammatory and anti-apoptotic effects of Gal-1 significantly alleviated MIRI in rats in the current study.…”

“…Other studies using MIRI rabbit models confirmed that apoptosis did not occur after reperfusion for 4 h following myocardial ischemia for 5 min (33,34). Additionally, no myocardial apoptosis was detected after 30 min of ischemia (35). However, after ischemia for 30 min and reperfusion for 4 h, cardiomyocytes exhibited marked apoptosis, suggesting that cardiomyocyte apoptosis is not only dependent on reperfusion injury, but also on the length of ischemia.…”