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Open AccessArticle

Cylindrospermopsin-Microcystin-LR Combinations May Induce Genotoxic and Histopathological Damage in Rats

1
Area of Toxicology, Faculty of Pharmacy, University of Sevilla, Profesor García González n2, 41012 Sevilla, Spain
2
University of Agricultural Sciences and Veterinary Medicine Cluj-Napoca, Calea Mănăștur 3-5, 400372 Cluj-Napoca, Romania
3
Department of Pharmacology, Toxicology and Legal and Forensic Medicine, Faculty of Veterinary Medicine, University of Córdoba, Campus de Rabanales, 14014 Córdoba, Spain
4
Animal Pathology Department. Faculty of Veterinary Medicine, University of Córdoba, Campus Universitario de Rabanales s/n, 14014 Cordoba, Spain
5
Instituto Maimonides de Investigación Biomédica de Córdoba (IMIBIC)-Hospital Universitario Reina Sofía de Córdoba-Universidad de Córdoba, Avenida Menendez Pidal s/n, 14006 Cordoba, Spain
*
Author to whom correspondence should be addressed.
Toxins 2020, 12(6), 348; https://doi.org/10.3390/toxins12060348
Received: 8 April 2020 / Revised: 21 May 2020 / Accepted: 23 May 2020 / Published: 26 May 2020
(This article belongs to the Special Issue Freshwater Algal Toxins: Monitoring and Toxicity Profile)
Cylindrospermopsin (CYN) and microcystins (MC) are cyanotoxins that can occur simultaneously in contaminated water and food. CYN/MC-LR mixtures previously investigated in vitro showed an induction of micronucleus (MN) formation only in the presence of the metabolic fraction S9. When this is the case, the European Food Safety Authority recommends a follow up to in vivo testing. Thus, rats were orally exposed to 7.5 + 75, 23.7 + 237, and 75 + 750 μg CYN/MC-LR/kg body weight (b.w.). The MN test in bone marrow was performed, and the standard and modified comet assays were carried out to measure DNA strand breaks or oxidative DNA damage in stomach, liver, and blood cells. The results revealed an increase in MN formation in bone marrow, at all the assayed doses. However, no DNA strand breaks nor oxidative DNA damage were induced, as shown in the comet assays. The histopathological study indicated alterations only in the highest dose group. Liver was the target organ showing fatty degeneration and necrotic hepatocytes in centrilobular areas, as well as a light mononuclear inflammatory periportal infiltrate. Additionally, the stomach had flaking epithelium and mild necrosis of epithelial cells. Therefore, the combined exposure to cyanotoxins may induce genotoxic and histopathological damage in vivo. View Full-Text
Keywords: in vivo; genotoxicity; cylindrospermopsin; microcystin-LR; micronucleus; comet assay; enzyme-modified comet assay; rats in vivo; genotoxicity; cylindrospermopsin; microcystin-LR; micronucleus; comet assay; enzyme-modified comet assay; rats
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Díez-Quijada, L.; Medrano-Padial, C.; Llana-Ruiz-Cabello, M.; Cătunescu, G.M.; Moyano, R.; Risalde, M.A.; Cameán, A.M.; Jos, Á. Cylindrospermopsin-Microcystin-LR Combinations May Induce Genotoxic and Histopathological Damage in Rats. Toxins 2020, 12, 348.

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