Table 4.
Summary of studies on cardiovascular toxicity of cyanobacterial cells and extracts containing cyanotoxins and purified cyanotoxins in fish, in vivo
| Cyanobacterial cells, extracts, purified toxins | Fish | Route | Doses | Duration | Acute/chronic | Cardiovascular effects | References |
|---|---|---|---|---|---|---|---|
| Microcystis aeruginosa PCC 7806 | Yearling carp | Oral | 400 µg MC-LReq/kg | 1, 3, 12, 24, 48, 72 h | Acute | Heart: no obvious micro-structural damage, no MC staining | Fischer and Dietrich (2000) |
| Disrupted Microcystis | Tenca (♂) | Oral | About 100, 220, 500, 1100 µg MC-LR/kg | 96 h | Acute | Heart: micro- and ultra-structural damage, loss of myofibrils | Atencio et al. (2008a) |
| Disrupted Microcystis | Nile tilapia (♂) | Oral | About 2400 µg MC-LR/kg | 24 h | Acute | Heart: micro- and ultra-structural damage, myofibrolysis, oedema, microhemorrages | Atencio et al. (2009) |
| Disrupted M. aeruginosa | Nile tilapia (♂) | Oral | About 2400 µg MC-LR/kg | 24, 48, 72 h | Acute | Heart: micro- and ultra-structural damage, myofibrolysis, hemorrhages, edema, lipid accumulation | Prieto et al. (2009) |
| Disrupted Microcystis | Nile tilapia (♂) | Oral | About 2400 µg MC-LR/kg | 24 h | Acute | Heart: micro- and ultra-structural damage | Puerto et al. (2010) |
| Microcystis blooms | Japanese medaka | Immersion | 120–7000 μg MC/L | 1–6 dpf | Acute | Heart rate↓ | Saraf et al. (2018) |
| cultured M. aeruginosa LE-3 | Japanese medaka | Immersion | 690–7838 μg MC/L | 1–6 dpf | Acute | Heart rate↓ | Saraf et al. (2018) |
| MC-LR | Japanese medaka | Immersion | 600–6300 μg/L | 1–6 dpf | Acute | Heart rate↓ | Saraf et al. (2018) |
| M. aeruginosa FACHB-905 | Zebrafish embryos | Immersion | 5, 10, 20 × 105 cells/L (6.7, 11.2, 24.6 µg MC/L) | 1–96 hpf | Acute | Heart rate↓, pericardial edemas | Li et al. (2021) |
| Crude extracts of M. aeruginosa HUB 5.3 | Zebrafish embryos | Immersion | 0.1% dry weight of suspended matter, 40 μg MC/L | Blastula stage up to end of embryonic period | Acute | Blood circulation↓, erythrocytes accumulated in heart and edema | Oberemm et al. (1997) |
| Crude extracts of field M. aeruginosa | Zebrafish embryos | Immersion | 0.1% dry weight of suspended matter, 30 μg MC/L | Blastula stage up to end of embryonic period | Acute | Blood circulation↓, erythrocytes accumulated in heart and edema | Oberemm et al. (1997) |
| Crude extracts of M. aeruginosa HUB 5–2-4 | Zebrafish embryos | Immersion | 0.02%, 0.1 w/v suspended dry matter, 40 μg MC/L | − | Acute | Blood circulation↓, erythrocytes accumulated in heart, hematomas, edema | Oberemm et al. (1999) |
| Crude extracts of field M. aeruginosa | Zebrafish embryos | Immersion | 0.02%, 0.1 w/v suspended dry matter, 30 μg MC/L | − | Acute | Blood circulation↓, erythrocytes accumulated in heart, hematomas, edema | Oberemm et al. (1999) |
| MC-LR | Zebrafish embryos | Immersion | 10 mg/L | 2 h (eleuthero-embryos) | Acute | Heart rate↓, pectoral edema | Oberemm et al. (1999) |
| Extracts of Microcystis PCC 7813 | Newly hatched brown trout alevins (2–7 dpf) | Immersion | 5, 50, 500 μg MC-LReq/L | 1, 2, 3 min, 24, 72 h | Acute | Heart rate↑, stroke volume↑, cardiac output↑ | Best et al. (2001) |
| MC-LR | Newly hatched brown trout alevins (2–7 dpf) | Immersion | 5, 50, 500 μg/L | 1, 2, 3 min, 24, 72 h | Acute | No significant changes of heart rate, stroke volume↑, cardiac output↑ | Best et al. (2001) |
| Extracts of M. aeruginosa KMF | Nile tilapia (♂) | i.p | 725 μg MC-LR/kg | 24 h, 7 days | Acute | Heart: LPO↑, SOD↓ | Pichardo et al. (2008) |
| Extracts of Microcystis spp. bloom | Crucian carp | i.p | 50, 200 MC-LReq/kg | 1, 3, 12, 24, 48 h | Acute | Mean arterial blood pressure↓, heart rate↑, circulating blood volume↓ | Li et al. (2009) |
| Crude extracts of M. aeruginosa bloom | Zebrafish | Immersion | 30 mg biomass/L | 36 h | Acute | Heart: micro-structural damage, edema, dissociation, congestion of blood vessels, cytoplasmic vacuolation, degenerative nuclei of myocardiocytes, DNA laddering, % double-stranded DNA↓ | Shahi et al. (2012) |
| Exudates of M. aeruginosa FACHB-905 | Sinocyclocheilus graham embryos | Immersion | 0.4–4 × 106 cells/mL | 1 hpf-10 dpf | Acute | Swollen pericardium heart dysplasia, protein S100A1↑, myosin light chain↓ | Zi et al. (2018) |
| Extracts of M. aeruginosa RST9501 | Trahira | i.p | 100 μg MC-LR/kg | 24 h | Acute | No significant changes of oxygen uptake, O2 extraction↓, heart rate↑ | Martins et al. (2019) |
| MC-LR | Loach embryos | Immersion | 0–500 μg/L | Post-fertilization, 32-cells, gastrula | Acute | Pericardial edema, tubular heart, bradycardia | Liu et al. (2002) |
| MC-LR | Nile tilapia (♂) | i.p | 500 μg/kg | 7 days | Acute | Heart: micro-structural damage, myopathy, fibrolysis | Atencio et al. (2008b) |
| MC-RR | Nile tilapia (♂) | i.p | 500 μg/kg | 7 days | Acute | Heart: micro-structural damage, myopathy, fibrolysis | Atencio et al. (2008b) |
| MC-LR | Zebrafish embryos | Immersion | 0.2, 0.5, 2, 5 mg/L | 0.5–96 hpf | Acute | Heart rate↓, heart malformations | Li et al. (2011) |
| MC-LR | Nile tilapia | i.p | 100 μg/kg | 48 h | Acute | Metabolic rate↓, critical O2 tension↑, heart rate↓ | Martins et al. (2011) |
| MC-LR | Zebrafish embryos | Immersion | 0.2, 0.5, 2, 5 mg/L | 0.5–96 hpf | Acute | Apoptosis in heart area | Zeng et al. (2014) |
| MC-RR | Zebrafish embryos | Immersion | 0.3, 1, 3 mg/L | 0.5–96 hpf | Acute | Heart rate↓ | Xie et al. (2015) |
| MC-LR | Zebrafish embryos | Immersion | 0.5,1, 2, 4, 6 µM | 0.5–96 hpf | Acute | Heart rate↓, apoptosis in heart area | Qi et al. (2016) |
| MC-LR | Zebrafish (♀♂) | Immersion | 1, 5, 25 μg/L | 60 days | Sub-chronic | F1 (5 dpf): pericardial edema | Wu et al. (2017) |
| MC-LR | Zebrafish embryos | Immersion | 1, 10, 100, 300 μg/L | 4–72 hpf | Acute | Heart rate↓ | Chen et al. (2018b) |
| MC-LR | Transgenic zebrafish (TG flk-1: GFP) embryos | Immersion | 50, 100, 500, 1000 nmol/L | 24–72 hpf | Acute | Caudal vein regions↓, deficiencies of dorsal longitudinal anastomotic vessels, inter-segmental arteries and veins | Wang et al. (2018) |
| MC-LR | Transgenic zebrafish Tg (Flk1:GFP) embryos | Immersion | 0.1, 1 μM | 24–72 hpf | Acute | Vessel: angiodysplasia, damaged vascular structures, suppressed and malformed blood vessels↑, lumen size↓, blood flow area↓, brain hemorrhage | Wang et al. (2019) |
| MC-LR | Transgenic zebrafish Tg (flk-1: EGFP) embryos | Immersion | 100, 1000 nM | 2–24 hpf | Acute | Dorsal aorta: rougher appearance and curved shape, curved PCV and growth inhibition, suppressed MceV, ISV sprouting↓ | Wang et al. (2021b) |
| MC-LR | Transgenic zebrafish Tg (fli1a: NGFP) embryos | Immersion | 100, 1000 nM | 2–72 hpf | Acute | EC migration from CHT↓ | Wang et al. (2021b) |
| MC-LR | Zebrafish (♀♂) | Immersion | 1, 5, 25 μg/L | 45 days | Sub-chronic | F1 (5 dpf): heart rate↓ | Cheng et al. (2017) |
| MC-LR | Zebrafish (♀♂) | Immersion | 0.9, 4.5, 22.5 μg/L | 21 days | Sub-chronic | F1 (5 dpf): heart rate↓ | Zuo et al. (2021) |
| MC-LR | Zebrafish (♂) | Immersion | 5, 20 μg/L | 6 weeks | Sub-chronic | F1 (96 hpf): heart rate↓ | Zhao et al. (2021) |
| NOD | Transgenic zebrafish Tg (flk-1: EGFP) embryos | Immersion | 0.5, 1, 2, 4 μM | 3–24, 48, 72, 96 hpf | Acute | Heart rate↑↓, pericardial edema, area of pericardium area↑, SV-BA distance↑, SV-BA distance/body length↑, DA width↓, DA-DLAV distance↓, ISV↓, SIV area↓, CCV area↑ | Chen et al. (2020b) |
| NOD | Transgenic zebrafish Tg (fli1a: NGFP) embryos | Immersion | 0.5, 1, 2, 4 μM | 3–72 hpf | Acute | EC migration from CHT↓ | Chen et al. (2020b) |
| NOD | Zebrafish embryos | Immersion | 0.5, 1, 2, 4 μM | 3–24, 120 hpf | Acute | Apoptosis in heart↑, vascular development-related genes DLL4 and VEGFC mRNA↑, CDH5 and VEGFA mRNA↓ | Chen et al. (2020b) |
| lyophilized Aphanizomenon ovalisporum LEGE-X001 | Nile tilapia (♂) | Oral | 200 µg CYN/kg | 24 h | Acute | Heart: micro- and ultra-structural damage, myofibrolysis, edema, hemorrhage | Gutiérrez-Praena et al. (2014) |
| CYN | Nile tilapia (♂) | Oral | 200 µg/kg | 24 h | Acute | Heart: micro- and ultra-structural damage, myofibrolysis, edema, hemorrhage | Gutiérrez-Praena et al. (2014) |
| Aphanizomenon ovalisporum LEGE-X001 | Nile tilapia (♂) | Immersion | 10 µg CYN/L and 0.46 µg deoxy-CYN/L, 100 µg CYN/L and 4.6 µg deoxy-CYN/L | 7, 14 days | Sub-chronic | Heart: micro- and ultra-structural damage, myofibrolysis, edema | Guzmán-Guillén et al. (2015) |
| lyophilized Aphanizomenon ovalisporum LEGE-X001 | Nile tilapia (♂) | Oral | 400 µg CYN/kg | 24 h | Acute | Heart: micro- and ultra-structural damage, myofibrolysis, loss of myofibrils, edema and hemorrhage, no significant changes of cardiac fibers diameter or capillaries diameter | Guzmán-Guillén et al. (2017) |
| CYN | Nile tilapia (♂) | Oral | 400 µg/kg | 24 h | Acute | Heart: micro- and ultra-structural damage, myofibrolysis, loss of myofibrils, edema and hemorrhage, no significant changes of cardiac fibers diameter or capillaries diameter | Guzmán-Guillén et al. (2017) |
| Oscillatoria sp. FACHB-528 | Zebrafish embryos | Immersion | 5, 10, 20 × 105 cells/L (8.5, 17.1, 35.1 µg CYN/L) | 1–96 hpf | Acute | No significant changes of heart rate | Li et al. (2021) |
| CYN | Nile tilapia (♂) | Gavage | 200 µg/kg | 24 h, 5d | Acute | Heart: micro- and ultra-structural damage, myofibrolysis, edema | Gutiérrez-Praena et al. (2012a) |
| CYN | Nile tilapia (♂) | i.p | 200 µg/kg | 24 h, 5d | Acute | Heart: micro- and ultra-structural damage, myofibrolysis, edema | Gutiérrez-Praena et al. (2012a) |
| CYN | Nile tilapia (♂) | gavage | 200, 400 µg/kg | 24 h | Acute | Heart: micro- and ultra-structural damage, fibrolysis | Puerto et al. (2014) |
| CYN | Nile tilapia (♂) | oral | 400 µg/kg | 24 h | Acute | Heart: myofibrolysis, edema, cardiac fibers diameter↓, capillaries diameter↑ | Guzmán-Guillén et al. (2016) |
| CYN | Transgenic zebrafish Tg (flk-1: EGFP) embryos | Immersion | 2, 20, 200, 2000 nM (0.9, 9, 90, 900 μg/L) | 48, 72 hpf | Acute | Damaged blood vessels in head, trunk and caudal tail region, deformed PCeV, CtA and PHS, incomplete and irregular development of ISV and DLAV, CCV area↑, ventral diameter↑, abnormal blood vessels↑, CCV remolding delay rate↑ | Wang et al. (2020a) |
| CYN | Zebrafish embryos | Immersion | 2, 20, 200, 2000 nM | 2–48, 72, 96 hpf | Acute | Area of pericardial edema↑, SV-BA distance↑, heart beat↓ | Wang et al. (2020b) |
| CYN | Transgenic zebrafish Tg (flk-1: EGFP) embryos | Immersion | 2, 20, 200, 2000 nM | 24–72 hpf | Acute | Blood vessels in brain↓, missing PCeV and PHS, deformity of DLV, CtA, PCeV and PHS | Wang et al. (2020b) |
| ATX-a | Zebrafish embryos | Immersion | 400 μg/L | Pec-fin stage (55 hpf), protruding-mouth stage (80 hpf) | Acute | Heart rate↓↑ | Oberemm et al. (1999) |
| STX | Transgenic zebrafish Tg (flk-1: EGFP) embryos | Immersion | 0.05, 0.1 μM | 3–24, 48, 72, 96 hpf | Acute | Cardiac rate↓, pericardial edema, DA width↑, DA-DLAV distance↓, ISV↓, ISV length↓, SIV area↓, CCV area↑ | Chen et al. (2020a) |
| STX | Zebrafish embryos | Immersion | 0.05, 0.1 μM | 3–24 hpf | Acute | DLL4 and VEGFC mRNA↑, no significant changes of CDH5 mRNA, VEGFA mRNA↓ | Chen et al. (2020a) |
↑ increased, ↓ decreased, dpf day(s) post-fertilization, hpf hour(s) post-fertilization, i.p. intraperitoneal, ATX-a anatoxin-a, CCV common cardinal vein, CHT caudal hematopoietic tissue, CtA central artery, CYN cylindrospermopsin, DA dorsal aorta, DLAV dorsal longitudinal anastomotic vessel, DLV dorsal longitudinal vein, EC endothelial cell, ISV inter-segmental vessel, LPO lipid peroxidation, MceV mid-cerebral veins, NOD nodularin, PCV posterior cardinal vein, PCeV posterior cerebral vein, PHS primary head sinus, SIV sub-intestinal vessels, SOD superoxide dismutase, STX saxitoxin, SV-BA sinus venosus–bulbus arteriosus