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