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Exposure to the Harmful Algal Bloom (HAB) Toxin Microcystin-LR (MC-LR) Prolongs and Increases Severity of Dextran Sulfate Sodium (DSS)-Induced Colitis

1
Department of Medicine, The University of Toledo College of Medicine and Life Sciences, Toledo, OH 43614, USA
2
Department of Pathology, The University of Toledo College of Medicine and Life Sciences, Toledo, OH 43614, USA
3
Department of Medical Microbiology and Immunology, The University of Toledo College of Medicine and Life Sciences, Toledo, OH 43614, USA
*
Authors to whom correspondence should be addressed.
Toxins 2019, 11(6), 371; https://doi.org/10.3390/toxins11060371
Received: 31 May 2019 / Revised: 20 June 2019 / Accepted: 22 June 2019 / Published: 25 June 2019
(This article belongs to the Special Issue Freshwater Algal Toxins: Monitoring and Toxicity Profile)
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Abstract

Inflammatory Bowel Disease (IBD) represents a collection of gastrointestinal disorders resulting from genetic and environmental factors. Microcystin-leucine arginine (MC-LR) is a toxin produced by cyanobacteria during algal blooms and demonstrates bioaccumulation in the intestinal tract following ingestion. Little is known about the impact of MC-LR ingestion in individuals with IBD. In this study, we sought to investigate MC-LR’s effects in a dextran sulfate sodium (DSS)-induced colitis model. Mice were separated into four groups: (a) water only (control), (b) DSS followed by water (DSS), (c) water followed by MC-LR (MC-LR), and (d) DSS followed by MC-LR (DSS + MC-LR). DSS resulted in weight loss, splenomegaly, and severe colitis marked by transmural acute inflammation, ulceration, shortened colon length, and bloody stools. DSS + MC-LR mice experienced prolonged weight loss and bloody stools, increased ulceration of colonic mucosa, and shorter colon length as compared with DSS mice. DSS + MC-LR also resulted in greater increases in pro-inflammatory transcripts within colonic tissue (TNF-α, IL-1β, CD40, MCP-1) and the pro-fibrotic marker, PAI-1, as compared to DSS-only ingestion. These findings demonstrate that MC-LR exposure not only prolongs, but also worsens the severity of pre-existing colitis, strengthening evidence of MC-LR as an under-recognized environmental toxin in vulnerable populations, such as those with IBD. View Full-Text
Keywords: inflammatory bowel disease; dextran sulfate sodium; colitis; microcystin; colon inflammatory bowel disease; dextran sulfate sodium; colitis; microcystin; colon
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Su, R.C.; Blomquist, T.M.; Kleinhenz, A.L.; Khalaf, F.K.; Dube, P.; Lad, A.; Breidenbach, J.D.; Mohammed, C.J.; Zhang, S.; Baum, C.E.; Malhotra, D.; Kennedy, D.J.; Haller, S.T. Exposure to the Harmful Algal Bloom (HAB) Toxin Microcystin-LR (MC-LR) Prolongs and Increases Severity of Dextran Sulfate Sodium (DSS)-Induced Colitis. Toxins 2019, 11, 371.

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