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Table 4 Overview of other (non-MC, non-CYN) cyanobacterial metabolites’ 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

Compound Experimental model Assays performed, endpoint Exposure conditions, concentration ranges Affected tissue(s) Main results References
In vivo
Cyanobacterial LPS Mouse (C57BL, female) Mortality 0.025–1.5 mg bacterial LPS (i.p.), co-injection of 750–850 µg CyP Whole organism Protection against LPS-induced septic shock after 8 h (25 ng LPS; 58% survival, D-galactosamine-sensitized mice) and after 24–40 h (1.5 mg, 80% survival, non-sensitized mice) [159]
“Limnothrixin” (from Limnothrix AC0243) Mouse (Balb/C, male) Histology 300 µL known toxin-free biomass extract (i.p.; extract 1: 180 mg dw/mL, extract 2: 195 mg dw/mL), 3–24 h Gastrointestinal tract, small intestine (duodenum) Loss of single cells/cell sheets in the duodenum; serum-colored mucoidal material in the gastrointestinal tract 3–10 h p.i. [194]
Cylindrospermopsis raciborskii biomass extract without detectable levels of CYN, MCs or saxitoxins Mouse (Charles River, male) Histology 1337–1572 mg dw/kg bw (i.p.), 8–24 h Intestines, immune system (mucosa-associated lymphoid tissue) Enlarged Peyer’s patches [195]
In vitro
Aeruginosins n.a. (biochemical) In vitro inhibitory assays (biochemical) n.a. n.a. Serine protease inhibition, IC50 = 0.03 − > 100 µg/mL [186]
Anabaenolysin A Human (primary erythrocytes) Hemoglobin release (necrosis) 0.38–3 µM Abl A; 1 h Blood EC50 (necrosis) ≈ 0.8 µM [191]
Cyanobacterial LPS Human (primary monocytes) ELISA, RT-PCR, FACS analysis 0.1–20 µg/mL cyanobacterial LPS + 1–10 µg/mL bacterial LPS; 0–16 h Blood (dendritic cells), innate immune system 20-fold excess of CyP compared to LPS completely inhibited cytokine production [159]
Cyanobacterial LPS Various Pyrogenicity (LAL test, PyroGene rFC assay), leukocyte activation (chemiluminescence) Cyanobacterial LPS extracts from M. aeruginosa-dominated bloom biomass (11 naturally occurring blooms) Immune system 10.2–78.3×104 EU/mg LPS (LAL test); 0.91–18.96×104 EU/mg LPS (PyroGene assay); leukocyte activation observed [157]
Cylindrospermopsin- containing biomass extracts n.a. Skin sensitization Human health risk assessment, literature review Skin, immune system Skin sensitization occurred in a cylindrospermopsin-independent manner, implying other irritating agents in the bloom biomass [176]
Cyanobacterial biomass (Spirulina platensis) hot water extract Human (blood, male volunteers) Cytokine production and responsiveness, natural killer cell cytolytic activity 50 mL extract/volunteer/day, 1–8 weeks Whole organism, blood Internalization of uncharacterized Spirulina components via GIT; prestimulation of monocytes. Targets: monocytes (additive effect on TLR-mediated cytokine production) and natural killer (NK) cells (upregulation of cytolysis and IFN; critically affected by IL-18 levels) [196]
Cyanopeptolin CP1020 Danio rerio (whole embryo) Transcriptomics 0.1–1 mg/L CP1020, 96 h Whole embryo Pathways altered ≥ 2-fold: DNA damage recognition and repair, circadian rhythm, response to light [189]
Puwainaphycin F, minutissamides A and C Human (CaCo-2 cells) ELISA Non-cytotoxic concentrations of PUWF, MIN A, MIN C; 24 h Intestine (colon) Increased secretion of IL-8, altered expression of tight junction protein [193]
Puwainaphycins F/G Mouse (YAC-1 cells), human (HeLa cells) MTT assay, intracellular Ca2+ concentration 1–10 µM PUW, 10 min–10 h Lymphoma, cervical cancer EC50 (necrosis) 2.2 µM [192]
  1. Abl A: anabaenolysin A, CyP: Cyanobacterial LPS-like compound; EC50: half-maximal effective concentration; ELISA: enzyme-linked immunosorbent assay; GIT: gastrointestinal tract; IC50: median inhibitory concentration; IFNγ: Interferon γ; IL: interleukin; LAL: Limulus amebocyte lysate; LOAEL/NOAEL: lowest/no-observed adverse effects level; LPS: lipopolysaccharide; MIN: minutissamide; PUW: puwainaphycin; n.a.: not applicable, TLR: toll-like receptor