Symmetric dimethyl arginine and N-acetyl- β-D-glucosaminidase lysosimyria of proximal renal tubules as a target for nephrotoxicity in patients with rheumatoid arthritis treated with disease modifying antirheumatic drugs.

Spasovski, Dejan; Latifi, Arif; Marina, Nada; Calovski, Jordan; Kafedziska, Irena; Božinovski, Gjorgi; Percinkova, Snežana; Slaninka-Micevska, Maja; Balkanov, Trajan; Dejanova, Beti; Alabakovska, S.; Krstevska-Balkanov, Svetlana; Spasovski, Goce

doi:10.5812/nephropathol.8989

Cited by 6 publications

(6 citation statements)

References 30 publications

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“…After the third methotrexate therapy, albumin concentration in urine was significantly increased pointing to methotrexate-induced damages of glomerules. These changes at the level of microalbuminuria persisting up to the end of the experiment are partially in accordance with earlier findings of Vujić et al [25] and Ferrari et al [26] and Spasovski et al [27].…”

Section: Discussionsupporting

confidence: 93%

Activities of Proximal Tubule Enzymes and Albumin Concentration in Urine of Children Treated With Methotrexate

Vujić¹,

Plavšić

Uletilović

et al. 2015

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In order to study methotrexate nephrotoxicity, the activities of proximal tubule epithelial cell membrane enzymes: alanine aminopeptidase (AAP) and gamma-glutamyltransferase (GGT), as well as of lysosomal N-acetyl-beta-D-glucosaminidase (NAG) and urinary albumin concentrations were determined in 12-h-urine samples of 30 patients with lymphoblastomous leukemia. The patients were i.v. receiving 4 individual methotrexate doses of 2000 mg/m2 every 15 days followed by leucovorin as a protector. Control and methotrexate-treated group, each consisting of 30 examinees, included 4–10 years old children of both sexes. Statistically significant increase of AAP and GGT activities, expressed as U/mmol creatinine was observed after the first two (p 0.05), as well as after the remaining two therapies (p 0.01) in relation to the control. Enzymatic activities of these two enzymes decreased to control value before the second and the third methotrexate application, but they increased again after the third application and remained elevated up to the end of experiments. Significant increase of NAG activity expressed as U/mmol creatinine (p 0.01), as well as urinary albumin levels (mg/mmol creatinine; p 0.01) were registered after the third methotrexate therapy and this elevation of the same statistical significance of the differences remained stable till the end of the therapy. Based on these results it can be concluded that during the time period of two first applications nephrotoxic methotrexate action is reversible and at the level of proximal tubule epithelial cell membranes. During the last two applications impairment is irreversible and at the level of cell organelles and glomerular filtration.

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Section: Discussionsupporting

confidence: 93%

Activities of Proximal Tubule Enzymes and Albumin Concentration in Urine of Children Treated With Methotrexate

Vujić¹,

Plavšić

Uletilović

et al. 2015

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“…Indeed, in proteinuric glomerular diseases, the increased excretion of NAG can occur even in the absence of morphological evidence of tubular cells damage, which probably reflects the increased lysosomal activity of these cells due to the increased uptake of filtered proteins. Therefore, NAG could be considered as an indicator of the functional status of the renal tubules as well as tubular damage . As a consequence, monocytes/macrophages could be infiltrated and cause structural glomerular damage through the release of proteolytic enzymes and oxygen radicals, or via the elaboration of cytokines.…”

Section: Discussionmentioning

confidence: 99%

“…Since the latter is one of the pro‐fibrogenic markers, one cannot neglect the involvement of fibrogenesis in CsA nephropathy. In addition, NAG is one of the enzymes involved in the degradation of one major component of extracellular matrix constituting the tubular structure of the kidney; therefore, the increase in such enzyme activity can add more to the destruction of renal tubules causing more nephrotoxicity …”

Section: Discussionmentioning

confidence: 99%

“…Therefore, NAG could be considered as an indicator of the functional status of the renal tubules as well as tubular damage. 46 As a consequence, monocytes/macrophages could be infiltrated and cause structural glomerular damage through the release of proteolytic enzymes and oxygen radicals, or via the elaboration of cytokines. In this study, it was demonstrated that the increase in urinary NAG, an indicator of renal tubular injury, was significantly and positively correlated with the elevation in the circulating levels of TGF-β.…”

Section: R E T R a C T E Dmentioning

confidence: 99%

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RETRACTED: Role of mesenchymal stem cells versus angiotensin converting enzyme inhibitor in kidney repair

et al. 2017

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“…This drawback is obviated by using chromogenic HEX(NAG) substrates that release dyes with longer wavelength absorption maxima bands. A current commercial colorimetric assay for HEX(NAG) detection uses sodium-3-cresolsulfonphthaleinyl- N -acetyl-β- d -glucosaminide (substrate 1 in Scheme ) and releases the intensely colored dye, meta-cresol purple, which is detected at 580 nm after the assay is stopped by increasing the assay pH to >9 (Figure c). − …”

Section: Assessing Kidney Healthmentioning

confidence: 99%

Advances in Optical Sensors of N-Acetyl-β-d-hexosaminidase (N-Acetyl-β-d-glucosaminidase)

Morsby

Smith

2022

Bioconjugate Chem.

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N-Acetyl-β-d-hexosaminidases (EC 3.2.1.52) are exo-acting glycosyl hydrolases that remove N-acetyl-β-d-glucosamine (Glc-NAc) or N-acetyl-β-d-galactosamine (Gal-NAc) from the nonreducing ends of various biomolecules including oligosaccharides, glycoproteins, and glycolipids. The same enzymes are sometimes called N-acetyl-β-d-glucosaminidases, and this review article employs the shorthand descriptor HEX(NAG) to indicate that the terms HEX or NAG are used interchangeably in the literature. The wide distribution of HEX(NAG) throughout the biosphere and its intracellular location in lysosomes combine to make it an important enzyme in food science, agriculture, cell biology, medical diagnostics, and chemotherapy. For more than 50 years, researchers have employed chromogenic derivatives of N-acetyl-β-d-glucosaminide in basic assays for biomedical research and clinical chemistry. Recent conceptual and synthetic innovations in molecular fluorescence sensors, along with concurrent technical improvements in instrumentation, have produced a growing number of new fluorescent imaging and diagnostics methods. A systematic summary of the recent advances in optical sensors for HEX(NAG) is provided under the following headings: assessing kidney health, detection and treatment of infectious disease, fluorescence imaging of cancer, treatment of lysosomal disorders, and reactive probes for chemical biology. The article concludes with some comments on likely future directions.

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Symmetric dimethyl arginine and N-acetyl- β-D-glucosaminidase lysosimyria of proximal renal tubules as a target for nephrotoxicity in patients with rheumatoid arthritis treated with disease modifying antirheumatic drugs.

Cited by 6 publications

References 30 publications

Activities of Proximal Tubule Enzymes and Albumin Concentration in Urine of Children Treated With Methotrexate

Activities of Proximal Tubule Enzymes and Albumin Concentration in Urine of Children Treated With Methotrexate

RETRACTED: Role of mesenchymal stem cells versus angiotensin converting enzyme inhibitor in kidney repair

Advances in Optical Sensors of N-Acetyl-β-d-hexosaminidase (N-Acetyl-β-d-glucosaminidase)

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