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Impact of Microcystin-LR on Liver Function Varies by Dose and Sex in Mice

Microcystin (MC) exposure is an increasing concern because more geographical locations are covered with cyanobacterial blooms as eutrophication and bloom-favoring environmental factors become more prevalent worldwide. Acute MC exposure has been linked to gastrointestinal distress, liver toxicity, an...

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Autores principales: Mrdjen, Igor, Morse, Mark A., Ruch, Randall J., Knobloch, Thomas J., Choudhary, Shambhunath, Weghorst, Christopher M., Lee, Jiyoung
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6266648/
https://www.ncbi.nlm.nih.gov/pubmed/30373283
http://dx.doi.org/10.3390/toxins10110435
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author Mrdjen, Igor
Morse, Mark A.
Ruch, Randall J.
Knobloch, Thomas J.
Choudhary, Shambhunath
Weghorst, Christopher M.
Lee, Jiyoung
author_facet Mrdjen, Igor
Morse, Mark A.
Ruch, Randall J.
Knobloch, Thomas J.
Choudhary, Shambhunath
Weghorst, Christopher M.
Lee, Jiyoung
author_sort Mrdjen, Igor
collection PubMed
description Microcystin (MC) exposure is an increasing concern because more geographical locations are covered with cyanobacterial blooms as eutrophication and bloom-favoring environmental factors become more prevalent worldwide. Acute MC exposure has been linked to gastrointestinal distress, liver toxicity, and death in extreme circumstances. The goal of this study was to provide an accurate and comprehensive description of MC-LRs impacts on liver pathology, clinical chemistry, and gap junction intercellular communication (GJIC) in CD-1 male and female mice. Mice were exposed to 0, 3000, and 5000/4000 µg/kg/day MC-LR, daily for 7 days, and were necropsied on Day 8. Blood samples for clinical chemistry analysis were processed to serum, while liver sections were fixed for histopathology or evaluated for GJIC using fluorescent cut-load dye. Results show a dose-dependent relationship with MC-LR exposure and hepatocellular hypertrophy, degradation, and necrosis. Clinical chemistry parameters alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin, and cholesterol increased significantly in MC-LR exposed mice. Clinical chemistry parameter analysis showed significantly increased susceptibility to MC-LR in females compared to males. Changes in GJIC were not noted, but localization of hepatotoxicity near the central veins and midlobular areas was seen. Future toxicity studies involving MCs should consider response differences across sexes, differing MC congeners, and combinatorial exposures involving other cyanotoxins.
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spelling pubmed-62666482018-12-07 Impact of Microcystin-LR on Liver Function Varies by Dose and Sex in Mice Mrdjen, Igor Morse, Mark A. Ruch, Randall J. Knobloch, Thomas J. Choudhary, Shambhunath Weghorst, Christopher M. Lee, Jiyoung Toxins (Basel) Article Microcystin (MC) exposure is an increasing concern because more geographical locations are covered with cyanobacterial blooms as eutrophication and bloom-favoring environmental factors become more prevalent worldwide. Acute MC exposure has been linked to gastrointestinal distress, liver toxicity, and death in extreme circumstances. The goal of this study was to provide an accurate and comprehensive description of MC-LRs impacts on liver pathology, clinical chemistry, and gap junction intercellular communication (GJIC) in CD-1 male and female mice. Mice were exposed to 0, 3000, and 5000/4000 µg/kg/day MC-LR, daily for 7 days, and were necropsied on Day 8. Blood samples for clinical chemistry analysis were processed to serum, while liver sections were fixed for histopathology or evaluated for GJIC using fluorescent cut-load dye. Results show a dose-dependent relationship with MC-LR exposure and hepatocellular hypertrophy, degradation, and necrosis. Clinical chemistry parameters alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin, and cholesterol increased significantly in MC-LR exposed mice. Clinical chemistry parameter analysis showed significantly increased susceptibility to MC-LR in females compared to males. Changes in GJIC were not noted, but localization of hepatotoxicity near the central veins and midlobular areas was seen. Future toxicity studies involving MCs should consider response differences across sexes, differing MC congeners, and combinatorial exposures involving other cyanotoxins. MDPI 2018-10-28 /pmc/articles/PMC6266648/ /pubmed/30373283 http://dx.doi.org/10.3390/toxins10110435 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Mrdjen, Igor
Morse, Mark A.
Ruch, Randall J.
Knobloch, Thomas J.
Choudhary, Shambhunath
Weghorst, Christopher M.
Lee, Jiyoung
Impact of Microcystin-LR on Liver Function Varies by Dose and Sex in Mice
title Impact of Microcystin-LR on Liver Function Varies by Dose and Sex in Mice
title_full Impact of Microcystin-LR on Liver Function Varies by Dose and Sex in Mice
title_fullStr Impact of Microcystin-LR on Liver Function Varies by Dose and Sex in Mice
title_full_unstemmed Impact of Microcystin-LR on Liver Function Varies by Dose and Sex in Mice
title_short Impact of Microcystin-LR on Liver Function Varies by Dose and Sex in Mice
title_sort impact of microcystin-lr on liver function varies by dose and sex in mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6266648/
https://www.ncbi.nlm.nih.gov/pubmed/30373283
http://dx.doi.org/10.3390/toxins10110435
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