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Comparative study on the effects of salinomycin,monensin and meso-2,3-dimercaptosuccinic acid on the concentrations of lead,calcium, copper,iron and zinc in lungs and heart in lead-exposed mice
Affiliation:1. Faculty of Medicine, Sofia University “St. Kliment Ohridski”, 1 Kozjak Street, 1407, Sofia, Bulgaria;2. Faculty of Chemistry and Pharmacy, Sofia University “St. Kliment Ohridski”, 1 James Bourchier Blvd., 1164, Sofia, Bulgaria;3. Institute of Experimental Morphology, Pathology and Anthropology with Museum – BAS, Acad. Georgi Bonchev Str., bl. 25, 1113, Sofia, Bulgaria;4. Chemistry Department, R&D, BIOVET JSC, 39 Peter Rakov Str., 4550, Peshtera, Bulgaria;1. Department of Biochemistry, Yuvaraja''s College, University of Mysore, Mysuru, 570005, Karnataka, India;2. Department of Basic Sciences, Deanship of Preparatory Year and Supporting Studies, Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam, 34212, Saudi Arabia;3. Department of Biotechnology, Yuvaraja''s College, University of Mysore, Mysuru, 570005, Karnataka, India;1. Institute of Earth Sciences, Academia Sinica, Taipei, 11529, Taiwan;2. Department of Pediatrics, Chang Gung Memorial Hospital, Taoyuan, 33305, Taiwan;3. School of Medicine, Chang Gung University, Taoyuan, 33302, Taiwan;1. Department of Psychiatry, Hospital Universitario de Getafe, Carretera de Toledo km.12.5 28905, Getafe, Madrid, Spain;2. Department of Laboratory Medicine, IML, IdiSSC, Hospital Clínico San Carlos, Calle Prof. Martín Lagos s/n, 28040, Madrid, Spain;3. Department of Neurology, Hospital de la Zarzuela, Calle de Pléyades 25, 28023, Madrid, Spain;4. Department of Epidemiology, IdiSSC, Hospital Clínico San Carlos, Calle Prof. Martín Lagos s/n, 28040, Madrid, Spain;5. Department of Public Health, University Francisco de Vitoria, Carretera Pozuelo a Majadahonda, Km 1.800, 28223 Pozuelo de Alarcón, Madrid, Spain;6. Department of Internal Medicine, Department of Medicine, Faculty of Medicine, Universidad Complutense de Madrid, IdiSSC, Hospital Clínico San Carlos, Calle Prof. Martín Lagos s/n, 28040, Madrid, Spain;7. Department of Pediatrics, Department of Public Health, Gynecology and Pediatrics, Faculty of Medicine, Universidad Complutense de Madrid, IdiSSC, Hospital Clínico San Carlos, Calle Prof. Martín Lagos s/n, 28040, Madrid, Spain;1. Laboratorio de Química Analítica para Investigación y Desarrollo (QUIANID), Instituto Interdisciplinario de Ciencias Básicas, Universidad Nacional de Cuyo, CONICET, Facultad de Ciencias Exactas y Naturales, Padre J. Contreras 1300, 5500, Mendoza, Argentina;2. Facultad de Farmacia y Bioquímica, Universidad Juan Agustín Maza, Lateral Sur del Acceso Este 2245, M5519, Guaymallén, Mendoza, Argentina;3. BRIN-USDS SOM Proteomics Facility, University of South Dakota, 414 E Clark St, Vermillion, SD, 57069, USA;4. Comisión Nacional de Energía Atómica, Gerencia Química, CONICET, Av. Gral. Paz 1499, B1650 Villa Maipú, Buenos Aires, Argentina;5. Laboratorio de Oncología, Instituto de Medicina y Biología Experimental de Cuyo (IMBECU-CONICET), Av. Dr. Adrian Ruiz Leal, Mendoza, Argentina
Abstract:Background and aimEnvironmental lead (Pb) exposure damages the lungs and is a risk factor for death from cardiovascular disease. Pb induces toxicity by a mechanism, which involves alteration of the essential elements homeostasis. In this study we compare the effects of salinomycin (Sal), monensin (Mon) and meso-2,3-dimercaptosuccinic acid (DMSA) on the concentrations of lead (Pb), calcium (Ca), copper (Cu), iron (Fe) and zinc (Zn) in the lungs and heart of lead-exposed mice.MethodsSixty days old male ICR mice were divided into five groups: control (Ctrl) – untreated mice obtained distilled water for 28 days; Pb-intoxicated group (Pb) – exposed to 80 mg/kg body weight (BW) Pb(NO3)2 during the first 14 days of the experimental protocol; DMSA-treated (Pb + DMSA) – Pb-exposed mice, subjected to treatment with an average daily dose of 20 mg/kg BW DMSA for two weeks; Monensin-treated (Pb + Mon) – Pb-exposed mice, obtained an average daily dose of 20 mg/kg BW tetraethylammonium salt of monensic acid for 14 days; Pb + Sal - Pb-exposed mice, treated with an average daily dose of 20 mg/kg BW tetraethylammonium salt of salinomycinic acid for two weeks. On the 29th day of the experiment the samples (lungs and heart) were taken for atomic absorption analysis.ResultsThe results revealed that exposure of mice to Pb for 14 days significantly increased the concentration of the toxic metal in both organs and elevated the cardiac concentrations of Ca, Cu and Fe compared to untreated mice. Pb exposure diminished the lung concentrations of Ca and Zn compared to that of untreated controls. DMSA, monensin and salinomycin decreased the concentration of Pb in the lungs and heart. Among the tested chelating agents, only salinomycin restored the cardiac Fe concentration to normal control values.ConclusionThe results demonstrated the potential application of polyether ionophorous antibiotic salinomycin as antidote for treatment of Pb-induced toxicity in the lungs and heart. The possible complexation of the polyether ionophorous antibiotics with Ca(II) and Zn(II), which can diminish the endogenous concentrations of both ions in the lungs should be taken into account.
Keywords:Lead  Essential elements  Chelating agents  Lung  Heart
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