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Table 3 Overview of cylindrospermopsin effects on the gastrointestinal tract and/or the (gut-associated) immune system

From: Effects of cyanobacterial toxins on the human gastrointestinal tract and the mucosal innate immune system

Experimental Model Assays performed, endpoint Exposure conditions, concentration ranges Affected tissue(s) Main results References
In vivo
 Mouse (MF1, male) Histology Cylindrospermopsis raciborskii culture extract containing 0.2% of CYN; 2.5–8.3 mg/kg CYNequiv. (gavage), 2–8 d Esophagus, stomach, small intestine Stomach ulceration, fresh blood in (small) intestinal content [133]
Mouse (Swiss albino) Body and organ weight, urine, serum, hematology analysis, histopathology CYN-containing cyanobacterial extract, 0–657 µg CYN/kg/day (p.o.), 10 weeks; purified CYN, 0–240-µg CYN/kg/day (p.o.), 11 weeks   NOAEL (TDI): 30 µg/kg/day; proposed guideline value for drinking water: 1 µg/L [131]
In vitro
Human (CaCo-2) Cytotoxicity (neutral Red uptake) Cylindrospermopsis raciborskii (CYLI29, CYN/MC-free methanolic extract), C. raciborskii (AWT205; 1.1-mg CYN/g dw; methanolic extract); 0.08–1.25 mg dw/mL, 48 h Intestine (colon) EC50: 0.4 ± 0.1 mg dw/ml (CYLI29), 1.3 ± 0.2 mg dw/ml (AWT205) [143]
Human (CaCo-2) Intestinal permeability, epithelial integrity (trans-epithelial electrical resistance, TEER) 1–10-µM CYN; 3–24 h Intestine (colon) 16.7–20.5% (intestinal permeability, apical-to-basolateral, after 24 h), epithelial integrity not significantly altered [99]
Human (CaCo-2) Protein content (Bradford assay), cell viability (MTS reduction), oxidative stress, intracellular GSH content, ultrastructural alteration 0.72–96.3-µM CYN 24–48 h Intestine (colon) LOEC: 1.44-µM (cell viability, ultrastructural alteration), 3.0 µM (intracellular ROS concentration), 6.0 µM (protein content, GSH content) [142]
Human (CaCo-2, C3A, HepG2, NCI-87, HCT-8, HuTu-80) Cell viability (MTT assay) 0.25–5-µM CYN, 1–7 days Intestine (colon), liver, stomach, small intestine (ileus, duodenum) Cellular sensitivity decreased in cell lines derived from more distal regions of the gastrointestinal tract: gastric > duodenal > ileal > colonic; EC50 = 6.5 ± 3.3 µM (CaCo-2) [144]
Human (CaCo-2) Permeability of pseudoepithelial layer 1.9–48.1-µM CYN, 24–48 h Intestine (colon) Apparent permeability: 3.45 × 10−7 cm/s (absorptive direction), 6.41 × 10−7 cm/s (secretive direction); epithelial permeability (increase): tenfold (absorptive), 0.7-fold (secretive); negligible transcellular passage [141]
Human (primary lymphocytes, whole blood) T-lymphocyte proliferation (thymidine incorporation) 1% biomass extract, 72 h (lymphocytes), 0.24 nM CYN, 72 h (whole blood) Blood, immune system Significant reduction of T-lymphocyte proliferation [138]
Human (primary peripheral blood neutrophils) Oxidative burst capacity (NADPH oxidase-mediated) 0.024–2.4-µM CYN, 1 h Blood/innate immune system (neutrophils) Significantly decreased ROS production at all CYN concentrations tested (LOEC = 0.024-µM CYN) by decreased NADPH oxidase-mediated ROS production in neutrophils; phagocytic activity unaffected [145]
Fish (Cyprinus carpio, isolated phagocytic cells) IL-1b expression (PCR), phagocytosis, oxidative stress 0.12–2.4-µM CYN, 24 h Immune system 32-fold increase in IL-1b expression (2.4 µM, 24 h); diminished phagocytosis (1.2 µM), ROS production increased (0.12 µM; LOEC) [146]
  1. CYN: cylindrospermopsin; EC50: half-maximal effective concentration; GSH: glutathione; IL: interleukin; LOAEL/NOAEL: lowest/no-observed adverse effects level; LOEC/NOEC: lowest/no-observed effect concentration; MC: microcystin; ROS: reactive oxygen species; TDI: tolerated daily intake