Effects of Salinomycin and Deferiprone on Lead-Induced Changes in the Mouse Brain

Author:

Petrova Emilia1ORCID,Gluhcheva Yordanka1,Pavlova Ekaterina1ORCID,Vladov Ivelin1ORCID,Dorkov Peter2,Schaier Martin3,Pashkunova-Martic Irena4ORCID,Helbich Thomas H.4ORCID,Keppler Bernhard5,Ivanova Juliana6ORCID

Affiliation:

1. Institute of Experimental Morphology, Pathology and Anthropology with Museum, Bulgarian Academy of Sciences, Acad. Georgi Bonchev Str., Bl. 25, 1113 Sofia, Bulgaria

2. Chemistry Department, Research and Development, BIOVET JSC, 39 Peter Rakov Street, 4550 Peshtera, Bulgaria

3. Institute of Analytical Chemistry, University of Vienna, 38 Waehringer Strasse, 1090 Vienna, Austria

4. Department 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, Austria

5. Institute of Inorganic Chemistry, University of Vienna, 42 Waehringer Strasse, 1090 Vienna, Austria

6. Faculty of Medicine, Sofia University “St. Kliment Ohridski”, Kozjak Str. 1, 1407 Sofia, Bulgaria

Abstract

Lead (Pb) is a highly toxic heavy metal that has deleterious effects on the central nervous system. This study aimed to investigate the effects of salinomycin (Sal) and deferiprone (DFP) on brain morphology and on the content of some essential elements in Pb-exposed mice. Adult male Institute of Cancer Research (ICR) mice were exposed to a daily dose of 80 mg/kg body weight ( b.w.) Pb(II) nitrate for 14 days and subsequently treated with Sal (16 mg/kg b.w.) or DFP (19 mg/kg b.w.) for another 14 days. At the end of the experimental protocol, the brains were processed for histological and inductively coupled plasma mass spectrometry (ICP-MS) analyses. Pb exposure resulted in a 50-fold increase in Pb concentration, compared with controls. Magnesium (Mg) and phosphorus (P) were also significantly increased by 22.22% and 17.92%, respectively. The histological analysis of Pb-exposed mice revealed brain pathological changes with features of neuronal necrosis. Brain Pb level remained significantly elevated in Sal- and DFP-administered groups (37-fold and 50-fold, respectively), compared with untreated controls. Treatment with Sal significantly reduced Mg and P concentrations by 22.56% and 18.38%, respectively, compared with the Pb-exposed group. Administration of Sal and DFP ameliorated brain injury in Pb-exposed mice and improved histological features. The results suggest the potential application of Sal and DFP for treatment of Pb-induced neurotoxicity.

Funder

Bulgarian National Science Fund

Austrian Federal Ministry of Education, Science and Research

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

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