The experimental model of nephrotic syndrome induced by Doxorubicin in rodents: an update

Pereira, Wagner de Fátima; Brito-Melo, Gustavo Eustáquio Alvim; Almeida, Cayo; Moreira, Lázaro Lopes; Cordeiro, Cleiton Willian; Carvalho, Thiago Guimarães Rosa; Mateo, Elvis Cueva; Silva, Ana Cristina Simões e

doi:10.1007/s00011-015-0813-1

Cited by 39 publications

(31 citation statements)

References 106 publications

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“…Moreover, there was a marked reduction of total nephrin most likely due to the loss of podocytes. This finding has been reported for ADR earlier [23], and is supported by our observation that podocyte numbers are strongly reduced in ADR at day 7. It should be kept in mind that an impaired perfusion with the magnetic particles due to advanced damage of the glomerular tuft could lead to a biased quantification of glomerular proteins.…”

Section: Discussionsupporting

confidence: 93%

A novel in vivo method to quantify slit diaphragm protein abundance in murine proteinuric kidney disease

et al. 2017

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Injury of the glomerular filter causes proteinuria by disrupting the sensitive interplay of the glomerular protein network. To date, studies of the expression and trafficking of glomerular proteins have been mostly limited to in vitro or histologic studies. Here, we report a novel in vivo biotinylation assay that allows the quantification of surface expression of glomerular proteins in mice. Kidneys were perfused in situ with biotin before harvest. Afterwards glomeruli were isolated and lyzed. The protein of interest was separated by immunoprecipitation and the amount of surface-expressed protein was quantified by Western blot analysis with streptavidin staining. As proof-of-concept, we examined the presence of nephrin in the slit diaphragm in two well-established murine models of proteinuric kidney disease: nephrotoxic nephritis and adriamycin nephropathy. In proteinuric animals, significantly less nephrin was detected in the slit diaphragm. When proteinuria decreased once again during the course of disease, the amount of surface nephrin returned to the baseline. Our present results suggest that our assay is a valuable tool to study the glomerular filter in proteinuric kidney diseases. Note that the assay is not limited to proteins expressed in the slit diaphragm, and all surface proteins that are accessible to biotin perfusion and immunoprecipitation qualify for this analysis.

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Section: Discussionsupporting

confidence: 93%

A novel in vivo method to quantify slit diaphragm protein abundance in murine proteinuric kidney disease

et al. 2017

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“…We should take into account that, in rats and mice, doxorubicin is very rapidly removed from the plasma after injection and deposited in tissues, especially in the kidney [ 38 ]. It is well known that a single and low dose of doxorubicin is sufficient to produce kidney tissue accumulation and histological pattern of focal segmental glomerulosclerosis (see, for review, [ 39 , 40 ]). Furthermore, the early presence of macrophages in renal tissue and the association of this finding with renal damage have been well characterized in doxorubicin-induced nephropathy [ 41 – 43 ].…”

Section: Discussionmentioning

confidence: 99%

Increased Migratory and Activation Cell Markers of Peripheral Blood Lymphocytes in an Experimental Model of Nephrotic Syndrome

Pereira

Brito-Melo

Carneiro

et al. 2015

Mediators of Inflammation

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The present study aimed to evaluate the expression of CD80 and CD18 in subpopulations of peripheral blood leukocytes and oxidative kidney damage in rats with nephrotic syndrome (NS) induced by doxorubicin (Dox) in comparison to control animals at different time points. Male adult Wistar rats were submitted to 24-hour urine and blood collection for biochemical and immunological analysis at 7, 14, 21, and 28 days after Dox injection. After euthanasia, the kidneys were removed for histological analysis and the evaluation of oxidative stress. The phenotypic characterization of leukocytes was performed using flow cytometry. Dox-injected animals exhibited increased CD18 expression in cytotoxic T lymphocytes, NK cells, and monocytes and high CD80 expression in monocytes. Kidney oxidative damage was positively correlated with CD80 expression in monocytes and serum levels of creatinine. These results suggest that phagocytic and cytotoxic cells are preferentially recruited to the tissue injury site, which may contribute to kidney dysfunction in this animal model of NS. The blockade of integrin and costimulatory molecules may provide new therapeutic opportunities for NS.

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“…The ADR-induced nephropathy model is a classical nephropathy animal model ( 16 , 30 ). In the present study, 2 weeks following ADR injection, the ADR group presented with minimal change in disease according to the electron microscopy results ( Fig.…”

Section: Resultsmentioning

confidence: 99%

“…The experimental animals were fasted in a metabolic cage to assess 24-h urine excretion. A 24-h urine excretion value of >100 mg ( 15 ) and foot process effacement of renal tissues detected by electron microscopy ( 16 ) indicated the successful establishment of the NS model. After 2 weeks, the rats from the two groups were sampled every 4 h over 24 h (3 rats/group at each time point, with a total of 18 normal rats and 18 NS rats).…”

Section: Methodsmentioning

confidence: 99%

An impaired hepatic clock system effects lipid metabolism in rats with nephropathy

et al. 2018

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Hyperlipidemia is a key clinical feature in patients with nephrotic syndrome (NS) that is associated with the incidence of cardiovascular events. Recent studies have suggested that the disorders of triglycerides, gluconeogenesis and liver glucose metabolism are associated with the abnormal transcription of clock genes. However, changes to the circadian rhythm of blood lipids in NS require further exploration, and the effects of NS on the hepatic clock system remain to be elucidated. In the present study, the impaired diurnal rhythm of the hepatic core clock genes (BMAL1, CLOCK, CRY1, CRY2, PER1 and PER2) significantly induced circadian rhythm abnormalities in liver-specific clock-controlled genes (LXR, CYP7A1, SREBP-1, ABCA1, DEC1 and DEC2; all P<0.05), which were significantly associated with the abnormal diurnal rhythms of triglyceride, total cholesterol, aspartate aminotransferase and alanine aminotransferase (all P<0.05) in rats with Adriamycin-induced nephropathy. Furthermore, a protein-protein interaction network was identified. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses based on the human database was conducted to obtain signaling pathway and correlation prediction analyses of overall human clock and clock-controlled gene correlations. Strong correlations of the aforementioned clock genes were detected (avg. local clustering coefficient, 0.849) which suggested significant enrichment in circadian rhythm signaling. The present results indicated that damage to hepatic clock systems may impact blood lipid circadian rhythm disorders in NS, and offer a starting point for understanding the crosstalk between peripheral organs and peripheral clock systems.

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The experimental model of nephrotic syndrome induced by Doxorubicin in rodents: an update

Cited by 39 publications

References 106 publications

A novel in vivo method to quantify slit diaphragm protein abundance in murine proteinuric kidney disease

A novel in vivo method to quantify slit diaphragm protein abundance in murine proteinuric kidney disease

Increased Migratory and Activation Cell Markers of Peripheral Blood Lymphocytes in an Experimental Model of Nephrotic Syndrome

An impaired hepatic clock system effects lipid metabolism in rats with nephropathy

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