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Comparative Effects of Deferiprone and Salinomycin on Lead-Induced Disturbance in the Homeostasis of Intrarenal Essential Elements in Mice

Lead (Pb) exposure induces severe nephrotoxic effects in humans and animals. Herein, we compare the effects of two chelating agents, salinomycin and deferiprone, on Pb-induced renal alterations in mice and in the homeostasis of essential elements. Adult male mice (Institute of Cancer Research (ICR))...

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Autores principales: Gluhcheva, Yordanka, Pashkunova-Martic, Irena, Schaier, Martin, Vladov, Ivelin, Stoykova, Silviya, Petrova, Emilia, Pavlova, Ekaterina, Dorkov, Peter, Helbich, Thomas H., Keppler, Bernhard, Ivanova, Juliana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9027580/
https://www.ncbi.nlm.nih.gov/pubmed/35457186
http://dx.doi.org/10.3390/ijms23084368
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author Gluhcheva, Yordanka
Pashkunova-Martic, Irena
Schaier, Martin
Vladov, Ivelin
Stoykova, Silviya
Petrova, Emilia
Pavlova, Ekaterina
Dorkov, Peter
Helbich, Thomas H.
Keppler, Bernhard
Ivanova, Juliana
author_facet Gluhcheva, Yordanka
Pashkunova-Martic, Irena
Schaier, Martin
Vladov, Ivelin
Stoykova, Silviya
Petrova, Emilia
Pavlova, Ekaterina
Dorkov, Peter
Helbich, Thomas H.
Keppler, Bernhard
Ivanova, Juliana
author_sort Gluhcheva, Yordanka
collection PubMed
description Lead (Pb) exposure induces severe nephrotoxic effects in humans and animals. Herein, we compare the effects of two chelating agents, salinomycin and deferiprone, on Pb-induced renal alterations in mice and in the homeostasis of essential elements. Adult male mice (Institute of Cancer Research (ICR)) were randomized into four groups: control (Ctrl)—untreated mice administered distilled water for 28 days; Pb-exposed group (Pb)—mice administered orally an average daily dose of 80 mg/kg body weight (BW) lead (II) nitrate (Pb(NO(3))(2)) during the first two weeks of the experimental protocol followed by the administration of distilled water for another two weeks; salinomycin-treated (Pb + Sal) group—Pb-exposed mice, administered an average daily dose of 16 mg/kg BW salinomycin for two weeks; deferiprone-treated (Pb + Def) group—Pb-exposed mice, administered an average daily dose of 20 mg/kg BW deferiprone for 14 days. The exposure of mice to Pb induced significant accumulation of the toxic metal in the kidneys and elicited inflammation with leukocyte infiltrations near the glomerulus. Biochemical analysis of the sera revealed that Pb significantly altered the renal function markers. Pb-induced renal toxicity was accompanied by a significant decrease in the endogenous renal concentrations of phosphorous (P), calcium (Ca), copper (Cu) and selenium (Se). In contrast to deferiprone, salinomycin significantly improved renal morphology in Pb-treated mice and decreased the Pb content by 13.62% compared to the Pb-exposed group. There was also a mild decrease in the renal endogenous concentration of magnesium (Mg) and elevation of the renal concentration of iron (Fe) in the salinomycin-treated group compared to controls. Overall, the results demonstrated that salinomycin is a more effective chelating agent for the treatment of Pb-induced alterations in renal morphology compared to deferiprone.
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spelling pubmed-90275802022-04-23 Comparative Effects of Deferiprone and Salinomycin on Lead-Induced Disturbance in the Homeostasis of Intrarenal Essential Elements in Mice Gluhcheva, Yordanka Pashkunova-Martic, Irena Schaier, Martin Vladov, Ivelin Stoykova, Silviya Petrova, Emilia Pavlova, Ekaterina Dorkov, Peter Helbich, Thomas H. Keppler, Bernhard Ivanova, Juliana Int J Mol Sci Article Lead (Pb) exposure induces severe nephrotoxic effects in humans and animals. Herein, we compare the effects of two chelating agents, salinomycin and deferiprone, on Pb-induced renal alterations in mice and in the homeostasis of essential elements. Adult male mice (Institute of Cancer Research (ICR)) were randomized into four groups: control (Ctrl)—untreated mice administered distilled water for 28 days; Pb-exposed group (Pb)—mice administered orally an average daily dose of 80 mg/kg body weight (BW) lead (II) nitrate (Pb(NO(3))(2)) during the first two weeks of the experimental protocol followed by the administration of distilled water for another two weeks; salinomycin-treated (Pb + Sal) group—Pb-exposed mice, administered an average daily dose of 16 mg/kg BW salinomycin for two weeks; deferiprone-treated (Pb + Def) group—Pb-exposed mice, administered an average daily dose of 20 mg/kg BW deferiprone for 14 days. The exposure of mice to Pb induced significant accumulation of the toxic metal in the kidneys and elicited inflammation with leukocyte infiltrations near the glomerulus. Biochemical analysis of the sera revealed that Pb significantly altered the renal function markers. Pb-induced renal toxicity was accompanied by a significant decrease in the endogenous renal concentrations of phosphorous (P), calcium (Ca), copper (Cu) and selenium (Se). In contrast to deferiprone, salinomycin significantly improved renal morphology in Pb-treated mice and decreased the Pb content by 13.62% compared to the Pb-exposed group. There was also a mild decrease in the renal endogenous concentration of magnesium (Mg) and elevation of the renal concentration of iron (Fe) in the salinomycin-treated group compared to controls. Overall, the results demonstrated that salinomycin is a more effective chelating agent for the treatment of Pb-induced alterations in renal morphology compared to deferiprone. MDPI 2022-04-15 /pmc/articles/PMC9027580/ /pubmed/35457186 http://dx.doi.org/10.3390/ijms23084368 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Gluhcheva, Yordanka
Pashkunova-Martic, Irena
Schaier, Martin
Vladov, Ivelin
Stoykova, Silviya
Petrova, Emilia
Pavlova, Ekaterina
Dorkov, Peter
Helbich, Thomas H.
Keppler, Bernhard
Ivanova, Juliana
Comparative Effects of Deferiprone and Salinomycin on Lead-Induced Disturbance in the Homeostasis of Intrarenal Essential Elements in Mice
title Comparative Effects of Deferiprone and Salinomycin on Lead-Induced Disturbance in the Homeostasis of Intrarenal Essential Elements in Mice
title_full Comparative Effects of Deferiprone and Salinomycin on Lead-Induced Disturbance in the Homeostasis of Intrarenal Essential Elements in Mice
title_fullStr Comparative Effects of Deferiprone and Salinomycin on Lead-Induced Disturbance in the Homeostasis of Intrarenal Essential Elements in Mice
title_full_unstemmed Comparative Effects of Deferiprone and Salinomycin on Lead-Induced Disturbance in the Homeostasis of Intrarenal Essential Elements in Mice
title_short Comparative Effects of Deferiprone and Salinomycin on Lead-Induced Disturbance in the Homeostasis of Intrarenal Essential Elements in Mice
title_sort comparative effects of deferiprone and salinomycin on lead-induced disturbance in the homeostasis of intrarenal essential elements in mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9027580/
https://www.ncbi.nlm.nih.gov/pubmed/35457186
http://dx.doi.org/10.3390/ijms23084368
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