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 (<i>Institute of Cancer Resear...

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Main Authors: Yordanka Gluhcheva, Irena Pashkunova-Martic, Martin Schaier, Ivelin Vladov, Silviya Stoykova, Emilia Petrova, Ekaterina Pavlova, Peter Dorkov, Thomas H. Helbich, Bernhard Keppler, Juliana Ivanova
Format: Article
Language:English
Published: MDPI AG 2022-04-01
Series:International Journal of Molecular Sciences
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Online Access:https://www.mdpi.com/1422-0067/23/8/4368
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author Yordanka Gluhcheva
Irena Pashkunova-Martic
Martin Schaier
Ivelin Vladov
Silviya Stoykova
Emilia Petrova
Ekaterina Pavlova
Peter Dorkov
Thomas H. Helbich
Bernhard Keppler
Juliana Ivanova
author_facet Yordanka Gluhcheva
Irena Pashkunova-Martic
Martin Schaier
Ivelin Vladov
Silviya Stoykova
Emilia Petrova
Ekaterina Pavlova
Peter Dorkov
Thomas H. Helbich
Bernhard Keppler
Juliana Ivanova
author_sort Yordanka Gluhcheva
collection DOAJ
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 (<i>Institute of Cancer Research</i> (<i>ICR</i>)) 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<sub>3</sub>)<sub>2</sub>) 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 doaj.art-1d4cdbc812984de78ae9e2334863b8652023-11-30T21:16:15ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-04-01238436810.3390/ijms23084368Comparative Effects of Deferiprone and Salinomycin on Lead-Induced Disturbance in the Homeostasis of Intrarenal Essential Elements in MiceYordanka Gluhcheva0Irena Pashkunova-Martic1Martin Schaier2Ivelin Vladov3Silviya Stoykova4Emilia Petrova5Ekaterina Pavlova6Peter Dorkov7Thomas H. Helbich8Bernhard Keppler9Juliana Ivanova10Institute of Experimental Morphology, Pathology and Anthropology with Museum, Bulgarian Academy of Sciences, Acad. Georgi Bonchev Street, Bl. 25, 1113 Sofia, BulgariaDepartment of Biomedical Imaging and Image-Guided Therapy, Division of Molecular and Structural Preclinical Imaging, Medical University of Vienna and General Hospital of Vienna, 18–20 Waehringer Guertel, 1090 Vienna, AustriaInstitute of Analytical Chemistry, University of Vienna, 38 Waehringer Strasse, 1090 Vienna, AustriaInstitute of Experimental Morphology, Pathology and Anthropology with Museum, Bulgarian Academy of Sciences, Acad. Georgi Bonchev Street, Bl. 25, 1113 Sofia, BulgariaFaculty of Chemistry and Pharmacy, Sofia University “St. Kliment Ohridski”, 1 J. Bourchier Blvd., 1164 Sofia, BulgariaInstitute of Experimental Morphology, Pathology and Anthropology with Museum, Bulgarian Academy of Sciences, Acad. Georgi Bonchev Street, Bl. 25, 1113 Sofia, BulgariaInstitute of Experimental Morphology, Pathology and Anthropology with Museum, Bulgarian Academy of Sciences, Acad. Georgi Bonchev Street, Bl. 25, 1113 Sofia, BulgariaChemistry Department, Research and Development, BIOVET JSC, 39 Peter Rakov Street, 4550 Peshtera, BulgariaDepartment of Biomedical Imaging and Image-Guided Therapy, Division of Molecular and Structural Preclinical Imaging, Medical University of Vienna and General Hospital of Vienna, 18–20 Waehringer Guertel, 1090 Vienna, AustriaInstitute of Inorganic Chemistry, University of Vienna, 42 Waehringer Strasse, 1090 Vienna, AustriaFaculty of Medicine, Sofia University “St. Kliment Ohridski”, 1 Kozjak Street, 1407 Sofia, BulgariaLead (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 (<i>Institute of Cancer Research</i> (<i>ICR</i>)) 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<sub>3</sub>)<sub>2</sub>) 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.https://www.mdpi.com/1422-0067/23/8/4368deferipronesalinomycinleadessential elementskidneys
spellingShingle Yordanka Gluhcheva
Irena Pashkunova-Martic
Martin Schaier
Ivelin Vladov
Silviya Stoykova
Emilia Petrova
Ekaterina Pavlova
Peter Dorkov
Thomas H. Helbich
Bernhard Keppler
Juliana Ivanova
Comparative Effects of Deferiprone and Salinomycin on Lead-Induced Disturbance in the Homeostasis of Intrarenal Essential Elements in Mice
International Journal of Molecular Sciences
deferiprone
salinomycin
lead
essential elements
kidneys
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 deferiprone
salinomycin
lead
essential elements
kidneys
url https://www.mdpi.com/1422-0067/23/8/4368
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