scholarly journals The Effectiveness of N-acetylcysteine in Alleviating Kidney Dysfunction in Ifosfamide-treated Rats

2020 ◽  
Vol 13 (1) ◽  
pp. 21-31
Author(s):  
Lukasz Dobrek ◽  
Klaudia Nalik-Iwaniak ◽  
Zbigniew Arent

Background: Renal damage and dysfunction are possible complications of pharmacotherapy with ifosfamide (IF), which also manifests urotoxic properties. A routine drug used to reduce the risk of IF-induced cystitis is mesna. Compounds with effect expected to be similar to mesna include N-acetylcysteine (NAC). Objective: The objective of the paper was histopathological verification of the uroprotective effect of NAC and assessment of whether this effect is accompanied by a potential nephroprotective effect. Methods: The experiment was conducted on 3 groups: 1 – control, sham-treated rats, 2 – animals treated with 5 times the IF dose administered i.p. (50 mg/kg b.w.) and 3 – rats treated with 5 times the IF dose administered i.p. + NAC administered p.o. (200 mg/kg b.w.). The renal function was evaluated analysing classical and new protein parameters (cystatin C - CysC, kidney injury molecule-1 – KIM-1 and nephrin - NPH) in blood and urine. Furthermore, histopathological analysis of bladders and kidneys was carried out. Results: Treatment with IF resulted in the development of cystitis, with no significant histopathological disturbances in the kidneys, and caused an increase in concentration and 24-hour excretion of CysC, KIM-1 NPH in the urine. Additional NAC administration caused a reduction of the said biochemical disturbances as well as improvement of the histopathological image of the urinary bladders. Conclusion: The IF therapy caused cystitis and kidney dysfunction of functional tubulopathy and early glomerulopathy character. Additional administration of NAC entailed improvement in the urinary bladder morphology and renal function. NAC is, thus, a compound exerting both uro- and nephroprotective effects.

2020 ◽  
Vol 14 (3) ◽  
pp. 150-162
Author(s):  
Lukasz Dobrek ◽  
Klaudia Nalik-Iwaniak ◽  
Kinga Fic ◽  
Zbigniew Arent

<b><i>Introduction</i></b>: Urotoxicity is a characteristic attribute of cy-clophosphamide and ifosfamide. Acetylcysteine is perceived as a uroprotective and possible nephroprotective compound. The purpose of the study was to assess the effect of acetylcysteine treatment on the morphology of the kidneys and the urinary bladder, and renal function in rats with cystitis induced by cyclophosphamide or ifosfamide. <b><i>Methods</i></b>: Cystitis was induced in rats belonging to groups 2 and 3, as well as 4 and 5, by five administrations of cyclophosphamide (75 mg/kg) or ifosfamide (80 mg/kg) respectively. Additionally, groups 3 and 5 received acetylcysteine (200 mg/kg). Group 1 was “sham treated” as a control. Upon conclusion of the experiment, the animals were euthanized and their kidneys and urinary bladders were collected for histopathological analysis. The assessment of renal function was based on classic nitrogen blood parameters (urea, creatinine, and uric acid), as well as proteinuria and cystatin C (CysC) and kidney injury molecule-1 (KIM-1) urinary concentrations, and their 24-hour elimination with urine. <b><i>Results</i></b>: Reduction of blood urea nitrogen and uric acid, and urinary pH with a significant increase of CysC and KIM-1 urinary concentrations, and their 24-hour elimination with urine were observed in groups 2 and 4. The acetylcysteine treatment did not cause a significant change of blood parameters, but significantly decreased 24-hour elimination of CysC and KIM-1 with urine, and accounted for alleviation of the histopathological abnormalities of urinary bladders, with no significant effects on the structure of the kidneys. <b><i>Conclusions</i></b>: Acetylcysteine used in the experimental model of cyclophosphamide- and ifosfamide-induced cystitis had a uroprotective effect and also reduced renal dysfunction, which suggests its potential use as a nephroprotective compound in cyclophosphamide/ifosfamide therapy.


2021 ◽  
Vol 75 (2) ◽  
pp. 138-142
Author(s):  
Vladimír Teplan

Accurate measurement of renal function in serious liver disease is very important not only for the estimation of renal damage (chronic kidney disease – CKD), safe drug management, prediction of illness follow-up, intensive methods including hemodialysis, hemodiafiltration or hemoperfusion, but also for the indication of liver transplantation. All methods of renal function measurement using serum creatinine for the estimation of glomerular filtration rate (GFR) are not accurate: they overestimate the value of GFR; the worse the liver damage is, the higher the level of overestimation; predominantly due to decreased endogenous creatinine production (creatinine generation rate – CGR). Using of cystatin C for GFR in liver disease is mainly promising in acute kidney injury (AKI), but obtained results have not been defi nitive yet and need more relevant data from diff erent methods of GFR estimation.


2016 ◽  
Vol 11 (2) ◽  
pp. 98 ◽  
Author(s):  
Michela Faggioni ◽  
◽  
Roxana Mehran ◽  

Contrast-induced acute kidney injury (CI-AKI) is characterised by a rapid deterioration of renal function within a few days of parenteral administration of contrast media (CM) in the absence of alternative causes. CI-AKI is the most common form of iatrogenic kidney dysfunction with an estimated prevalence of 12 % in patients undergoing percutaneous coronary intervention. Although usually selfresolving, in patients with pre-existing chronic kidney disease (CKD) or concomitant risk factors for renal damage, CI-AKI is associated with increased short- and long-term morbidity and mortality. Therefore, risk stratification based on clinical and peri-procedural characteristics is crucial in selecting patients at risk of CI-AKI who would benefit the most from implementation of preventive measures.


2018 ◽  
Vol 2 ◽  
pp. 239784731880507 ◽  
Author(s):  
Placido Rojas-Franco ◽  
Margarita Franco-Colín ◽  
María Estela Meléndez Camargo ◽  
María Mirian Estévez Carmona ◽  
María del Rocío Elizabeth Ortíz-Butrón ◽  
...  

Arthrospira maxima ( Spirulina) is considered a nutraceutical or functional food because it provides health benefits and it is used as nephroprotector because it contains nucleophilic compounds as phycobiliproteins and phycocyanin that prevent oxidative stress and cellular damage process. Also, it is known that inorganic mercury is bioaccumulated and exerted kidney toxicity. Despite the nephroprotective effect of Spirulina and its components, there is not enough information about the effect of them on renal function as well as the apoptosis process inhibition. This work aimed to investigate whether phycobiliproteins and phycocyanin of Spirulina can improve HgCl2-related glomerular and tubular renal dysfunction as well as the Bax, Bcl2, and effectors caspases alterations. Male mice were administrated with Spirulina, phycobiliproteins or phycocyanin 30 min before 5 mg/Kg HgCl2 administration. The nutraceuticals were administrated for the next 5 days. Then, the mice were euthanized. The renal function, caspases 3 and 9 activities, as well as Bax and Bcl2 expression were evaluated. Spirulina and its components prevent HgCl2-related apoptosis induction and glomerular dysfunction. We concluded that phycobiliproteins and phycocyanin of Spirulina reduce glomerular damage but not the tubular dysfunction in a mercury-related acute kidney injury.


2013 ◽  
Vol 35 ◽  
pp. 567-572 ◽  
Author(s):  
Sanja Simic Ogrizovic ◽  
Suzana Bojic ◽  
Gordana Basta-Jovanovic ◽  
Sanja Radojevic ◽  
Jelena Pavlovic ◽  
...  

Objectives. Retrospective study was designed to examine the importance of tissue kidney injury molecule-1 (KIM-1) expression in predicting kidney function in sixty patients (27 males) aged 34.15 ± 12.23 years with different kidney diseases over three years after kidney biopsy.Materials and Methods. Tissue KIM-1 expression was determined immunohistochemically and KIM-1 staining was scored semiquantitatively, as well as tubulointerstitialis (TIN), inflammation, atrophy, and fibrosis. Kidney function (MDRD formula) and proteinuria/day were evaluated at the time of biopsy (GFR0) and 6, 12, 24, and 36 months later.Results. Significantly positive correlations between tissue KIM-1 expression and age (r=0.313), TIN inflammation (r=0.456), fibrosis (r=0.317), and proteinuria at 6 months (r=0.394) as well as negative correlations with GFR0 (r=−0.572), GFR6 (r=−0.442), GFR24 (r=−0.398), and GFR36 (r=−0.412) were found. Meanwhile, TIN inflammation was the best predictor of all measured kidney functions during three years, while tissue KIM-1 expression (P=0.016) was a predictor only at 6 months after biopsy.Conclusion. Tissue KIM-1 expression significantly predicts kidney function solely at 6 months after biopsy, when the effects of immune and nonimmune treatments are the strongest.


2020 ◽  
Vol 21 (15) ◽  
pp. 5490 ◽  
Author(s):  
Satoshi Washino ◽  
Keiko Hosohata ◽  
Tomoaki Miyagawa

Partial or complete obstruction of the urinary tract is a common and challenging urological condition caused by a variety of conditions, including ureteral calculi, ureteral pelvic junction obstruction, ureteral stricture, and malignant ureteral obstruction. The condition, which may develop in patients of any age, induces tubular and interstitial injury followed by inflammatory cell infiltration and interstitial fibrosis, eventually impairing renal function. The serum creatinine level is commonly used to evaluate global renal function but is not sensitive to early changes in the glomerular filtration rate and unilateral renal damage. Biomarkers of acute kidney injury are useful for the early detection and monitoring of kidney injury induced by upper urinary tract obstruction. These markers include levels of neutrophil gelatinase-associated lipocalin (NGAL), monocyte chemotactic protein-1, kidney injury molecule 1, N-acetyl-b-D-glucosaminidase, and vanin-1 in the urine and serum NGAL and cystatin C concentrations. This review summarizes the pathophysiology of kidney injury caused by upper urinary tract obstruction, the roles played by emerging biomarkers of obstructive nephropathy, the mechanisms involved, and the clinical utility and limitations of the biomarkers.


2006 ◽  
Vol 291 (2) ◽  
pp. F456-F464 ◽  
Author(s):  
Mirjan M. van Timmeren ◽  
Stephan J. L. Bakker ◽  
Vishal S. Vaidya ◽  
Veronique Bailly ◽  
Theo A. Schuurs ◽  
...  

Kim-1, a recently discovered membrane protein, is undetectable in normal kidneys but markedly induced in proximal tubules after ischemic and toxic injury. The function of Kim-1 is unclear, but it is implicated in damage/repair processes. The Kim-1 ectodomain is cleaved by metalloproteinases and detectable in urine. We studied Kim-1 in a nontoxic, nonischemic, model of tubulointerstitial damage caused by acute proteinuria. Uninephrectomized (NX) rats received daily (ip) injections of 2 g BSA (NX+BSA, n = 12) or saline (NX, n = 6) for 3 wk. Kidneys were stained for various damage markers by immunohistochemistry (IHC). Kim-1 mRNA (RT-PCR, in situ hybridization), protein (IHC, Western blotting), and urinary Kim-1 (Luminex) were determined. Spatial relations between Kim-1 and other damage markers were studied by double labeling IHC. NX+BSA rats developed massive proteinuria (1,217 ± 313 vs. 18 ± 2 mg/day in NX, P < 0.001) and significant renal damage. Kim-1 mRNA was upregulated eightfold in NX+BSA (ratio Kim-1/β-actin, 4.08 ± 2.56 vs. 0.52 ± 0.64 in NX, P < 0.001) and localized to damaged tubules. Kim-1 protein expression was markedly induced in NX+BSA (2.46 ± 1.19 vs. 0.39 ± 0.10% staining/field in NX, P < 0.001). Urinary Kim-1 was significantly elevated in NX+BSA (921 ± 592 vs. 87 ± 164 pg/ml in NX, P < 0.001) and correlated with tissue Kim-1 expression ( r = 0.66, P =0.02). Kim-1 protein was found at the apical membrane of dilated nephrons. Kim-1 expression was limited to areas with inflammation (MØ), fibrosis (α-smooth muscle actin), and tubular damage (osteopontin), and only occasionally with tubular dedifferentiation (vimentin). These results implicate involvement of Kim-1 in the pathogenesis of proteinuria-induced renal damage/repair. Urinary Kim-1 levels may serve as a marker of proteinuria-induced renal damage.


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