Journal Article
Exposure to the Harmful Algal Bloom (HAB) Toxin Microcystin-LR (MC-LR) Prolongs and Increases Severity of Dextran Sulfate Sodium (DSS)-Induced Colitis
Su, RC; Blomquist, TM; Kleinhenz, AL; Khalaf, FK; Dube, P; Lad, A; Breidenbach, JD; Mohammed, CJ; Zhang, S; Baum, CE; Malhotra, D; Kennedy, DJ; Haller, ST
Toxins
ISSN: 2072-6651
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.
Colitis; Colon; Dextran sulfate sodium; Inflammatory bowel disease; Microcystin; CD40 antigen; dextran sulfate; interleukin 1beta; leucine; microcystin; microcystin LR; monocyte chemotactic protein 1; mucin; tumor necrosis factor; CD40 antigen; cytokine; dextran sulfate; microcystin; microcystin LR; algal bloom; animal experiment; animal model; animal tissue; Article; ascending colon; body weight; body weight loss; colon mucosa; colon tissue; colon ulcer; controlled study; cytokine production; descending colon; dextran sulfate sodium-induced colitis; disease exacerbation; disease severity; goblet cell; histopathology; inflammatory bowel disease; innate immunity; male; mouse; nonhuman; occult blood; practice guideline; rectum hemorrhage; spleen weight; splenomegaly; algal bloom; animal; C57BL mouse; colitis; colon; drug effect; gene expression; genetics; metabolism; pathology; severity of illness index; spleen; Animals; CD40 Antigens; Colitis; Colon; Cytokines; Dextran Sulfate; Gene Expression; Harmful Algal Bloom; Male; Mice, Inbred C57BL; Microcystins; Severity of Illness Index; Spleen