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Ameliorative effect of the anticancer agent salinomycin on cadmium-induced hepatotoxicity and renal dysfunction in mice

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Abstract

This study presents experimental data on the effects of the tetraethylammonium salt of salinomycinic acid (Sal) on Cd-induced hepatotoxicity and renal dysfunction in Cd-treated mice compared to those of meso-2,3-dimercaptosuccinic acid (DMSA). Forty 60-day-old male ICR mice were randomized into five groups: control group (untreated mice), Cd group (Cd(II) acetate 20 mg/kg body weight provided orally once per day for 14 days), Cd + DMSA group (exposed to Cd(II) acetate as the Cd-exposed group followed by DMSA 20 mg/kg body weight provided orally once per day for 14 days), and Cd + Sal group (exposed to Cd(II) acetate as the Cd-exposed group followed by Sal 20 mg/kg body weight once per day for 14 days). Cd intoxication of mice induced significant liver and kidney injury and a significant elevation of the concentration of Cd in both organs. Treatment of Cd-exposed mice with DMSA or Sal restored the levels of the renal and hepatic functional markers and significantly decreased the concentration of the toxic metal ion in both organs. Administration of Sal improved Cd-induced alterations of the endogenous levels of the essential metal ions. Histological studies revealed that the antibiotic more effectively ameliorated the Cd effect on the liver morphology compared to DMSA. Taken together, the results confirm that the anticancer agent salinomycin is a promising antidote to Cd poisoning.

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Acknowledgements

The authors are grateful to the Sofia University “St. Kliment Ohridski” Science Fund (grant №5/2016, PI: Juliana Ivanova) and to the European Social Fund and Republic of Bulgaria, Operational Programme “Human Resources Development” 2007-2013 framework, grant № BG051PO001-3.3.06-0048 from 04.10.2012 for the financial support of this study. The authors thank Professor S. Arpadjan for the atomic absorption analysis of the mouse tissues. The authors are grateful to Assoc. Prof. A. Nakov, P. Dorkov (BIOVET Ltd., Bulgaria) for supplying the sodium salinomycin.

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Correspondence to Juliana Ivanova.

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This experimental protocol was approved by the Ethics Committee of the Institute of Experimental Morphology, Pathology and Anthropology with the Museum of the Bulgarian Academy of Science (approval number: 15/03/2016).

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The authors declare that they have no conflict of interest.

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Responsible editor: Philippe Garrigues

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Kamenova, K., Gluhcheva, Y., Vladov, I. et al. Ameliorative effect of the anticancer agent salinomycin on cadmium-induced hepatotoxicity and renal dysfunction in mice. Environ Sci Pollut Res 25, 3616–3627 (2018). https://doi.org/10.1007/s11356-017-0755-y

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  • DOI: https://doi.org/10.1007/s11356-017-0755-y

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