Table 2.

Summary of studies on cardiovascular toxicity by whole cells and crude extracts of cyanobacteria and purified cyanotoxins in mammals in vivo

Cyanobacterial cells, extracts and purified cyanotoxins	Mammals	Route	Doses	Duration	Acute/chronic	Cardiovascular effects	References
Microcystis aeruginosa NRC1	Mice	i.p	40, 80, 160 mg cyanobacteria/kg	3.8 h	Acute	Swelling, loss of cross-striation and pigmentation of myocardial fibres	Konst et al. (1965)
M. aeruginosa NRC1	Mice	Oral	3.2, 6.4, 12.8 g cyanobacteria/kg	4 h	Acute	Swelling, loss of cross-striation and pigmentation of myocardial fibres	Konst et al. (1965)
M. aeruginosa NRC1	Guinea pig	i.p	80, 160, 320 mg cyanobacteria/kg	4 h	Acute	Partly coagulated residual blood in the heart and large vessels	Konst et al. (1965)
M. aeruginosa NRC1	Guinea pig	Oral	1.6, 3.2, 6.4, 12.8 g cyanobacteria/kg	12 h	Acute	Partly coagulated residual blood in the heart and large vessels	Konst et al. (1965)
M. aeruginosa NRC1	Rabbit	Oral	1.6, 3.2, 6.4, 12.8 g cyanobacteria /kg	30 h	Acute	Tachycardia, rapid heart action, partly coagulated residual blood in the heart and large vessels, swelling, loss of cross-striation and pigmentation of myocardial fibres	Konst et al. (1965)
M. aeruginosa NRC1	Lamb	Oral	16 g cyanobacteria /kg	19 h	Acute	Accelerated heart action, petechial haemorrhages in coronary fat, swelling, loss of cross-striation and pigmentation of myocardial fibres	Konst et al. (1965)
M. aeruginosa NRC1	Calf	Oral	9.6, 32 g cyanobacteria /kg	28 h	Acute	Accelerated heart action, systolic murmurs	Konst et al. (1965)
M. aeruginosa M228 extract	Jcl:ICR mice (♂)	i.p	10–20 mg dry cells/kg	1 h	Acute	No significant changes of heart weight, contracted abdominal vascular system, decreased R-wave voltage, ST-segment depression, tachycardia development and terminal bradycardia, atrial fibrillation	Oishi and Watanabe (1986)
Cyanobacterial crude extracts	Wistar rats (♂)	i.v	80 µg MC-LReq/kg (1 LD50)	1, 2, 4, 6, 12, 24 h	Acute	Heart: MC-LR and -RR accumulation	Wang et al. (2008)
Crude extracted MCs, mainly -RR and -LR	Rabbits (♂)	i.p	12.5, 50 μg/kg	1, 3, 12, 24, 48 h	Acute	Heart mitochondria: ultra-structural damage, MDA↑, SOD and SDH activities↑, Ca2+-Mg2+-ATPase↓, no significant changes of NADH dehydrogenase or Na+-K+-ATPase	Zhao et al. (2008)
Crude extracted MCs	Wistar rats (♂)	i.v	14, 87 µg MC-LReq/kg (0.16, 1 LD50)	24 h	Acute	Heart rate↓, mean arterial pressure↓, plasma: ALT↑, ALP↑, AST↑, LDH↑, CK↑, cTn I↑; heart: MCs accumulation, micro- and ultra-structural damage, cytosol CAT, GST, SOD and GPX activities↑, cytosol GSH and MDA↑, mitochondrial complex I and III↓, no significant changes of complex II, mitochondrial MDA↑, CAT, GST, SOD and GPX mRNA↑	Qiu et al. (2009)
Crude extracted MCs	Wistar rats (♂)	i.v	14 µg MC-LReq/kg (0.16 LD50)	2, 4, 6 h	Acute	Heart: apoptosis↑, p53, Bax, Bcl-2, caspase-3 and caspase-9 mRNA↑	Qiu (2014)
MC-LR	Fischer 344 rats (♂)	i.v	50, 100 μg/kg	30, 60, 120, 240, 480 min	Acute	Arterial blood pressure↓, heart rate↓, cardiac output↓, stroke volume↓, body temperature↓, O2 consumption↓, CO2 production↓, metabolic rate↓, respiratory exchange ratio↑, no significant changes of relative tidal volume, arterial acid–base balance changes, arterial lactate↑	LeClaire et al. (1995)
MC-LR	Cross-bred, pigs (♀)	i.v	25, 72 μg/kg	45, 90, 150, 210, 300 min	Acute	Mean aortic pressure↓, central venous pressure↓, portal venous pressure↑, hepatic and renal perfusion↓, pO2↑, O2 saturation↑, pCO2↓	Beasley et al. (2000)
MC-LR	Aged ICR mice (♂)	Oral	500 μg/kg/time	1, 6, 7, 12, 13 weeks	Sub-chronic	Heart: MC staining in blood plasma	Ito et al. (2000)
MC-LR	Young ICR mice (♂)	Oral	500 μg/kg/4 weeks	16 weeks	Sub-chronic	Heart: no MC staining	Ito et al. (2000)
MC-LR	Wistar rats (♂)	i.p	10 μg/kg/2 days	8 months	Chronic	Heart: micro-structural damage, loss of cell cross-striations, mononuclear infiltration in the interstitial tissue, cardiomyocytes↑, myofibril volume fraction↓, fibrosis↑, no significant changes of apoptosis	Milutinović et al. (2006)
MC-YR	Wistar rats (♂)	i.p	10 μg/kg/2 days	8 months	Chronic	Heart: micro-structural damage, fibrous proliferation, lymphocyte infiltration, bizarre-shaped nuclei, volume density↓, cardiomyocytes↑, myofibril volume fraction↓, no significant changes of apoptosis	Šuput et al. (2010)
MC-LR	N:NIH-S mice (♂)	i.p	25 μg/kg/2 days	1 month	Sub-chronic	Heart: no obvious DNA fragmentation, no significant changes of BAX, Bcl-2, α-tubulin, CaMKII or MAPK proteins	Lezcano et al. (2012)
MC-LR	KM (Kunming) mice (♂)	i.p	3.125, 6.25, 12.5, 25 μg/kg/day	7 days	Sub-chronic	Heart: no MCs accumulation	Huang et al. (2013)
MC-LR	C57 BL/6 mice (♂)	i.p	20 μg/kg/day	28 days	Sub-chronic	Liver and lung: microvascular permeability, CXCR2 and p-VE-cadherin proteins↑; liver, lung and heart: vascular leakage; serum: TNF-α, IL-1β, IL-6 and IL-8↑	Chen et al. (2018c)
MC-LR	BALB/c mice (♂)	Drinking water	1, 7.5, 15, 30 μg/L	6 months	Chronic	F1 (PD180, ♀♂): no micro-structural changes of heart	Meng et al. (2020)
Cylindrospermopsis raciborskii PHAWT/M	MF1 mice (♂)	Gavage	2.5–8.3 CYN mg/kg	48, 72 h	Acute	Heart: micro-structural damage, subepicardial and myocardial hemorrhages, loss of fiber striation, homogeneous pink staining, pyknotic nuclei	Seawright et al. (1999)
Extract of C. raciborskii AWQC CYP-026 J	Swiss albino mice (♂)	i.p	250, 500, 1000 mg cells/kg	48 h	Acute	Acute heart failure	Bernard et al. (2003)
CYN	ICR mice (♂)	i.p	0.2 mg/kg	l6, 24, 32, 40, 48, 72, 80, 100 h	Acute	Single cell necroses	Terao et al. (1994)
Extract of Anabaena flos-aquae UTEX 2383	Wistar rats (♂)	i.v	1.5, 3, 4.5, 6, 7.5 mg extract/kg	30 min	Acute	Heart rate↑↓, mean arterial blood pressure↑	Dube et al. (1996)
( ±)ATX-a	Sprague Dawley rats (♂)	i.v	10, 30, 100, 300 µg/kg	30 min	Acute	Mean arterial pressure↑, heart rate↓, cardiac index↑, no significant changes of total peripheral resistance index, hindquarter blood flow↑, no significant changes of hindquarter vascular resistance, renal and mesenteric blood flow↓, renal and mesenteric vascular resistance↑, plasma epinephrine↑, no significant changes of plasma norepinephrine	Sirén and Feurstein (1990)
( ±)ATX-a	Sprague Dawley rats (♂)	i.c.v	10, 30, 100, µg/kg	30 min	Acute	Mean arterial pressure↑, heart rate↓, no significant changes of hindquarter blood flow or hindquarter vascular resistance, renal and mesenteric blood flow↓, renal and mesenteric vascular resistance↑	Sirén and Feurstein (1990)
( +)ATX-a	Sprague Dawley rats (♂)	i.v	1, 3, 10, 30, 100, 300 µg/kg	30 min	Acute	Mean arterial pressure↑, heart rate↓, pO2↓, pCO2↑, acidosis	Adeyemo and Sirén (1992)
( ±)ATX-a	Sprague Dawley rats (♂)	i.v	1, 3, 10, 30, 100, 300 µg/kg	30 min	Acute	Mean arterial pressure↑, heart rate↓, pO2↓, pCO2↑, no significant changes in arterial blood acid–base balance	Adeyemo and Sirén (1992)
GNTX	Sprague Dawley rats (♂)	i.v	3.5 µg/kg/min	10 min	Acute	Blood pressure↓, ↑, no significant changes of heart rate	Cook et al. (1990)
STX	Hanky albino guinea pigs	i.p	10 µg/kg	10, 15 min	Acute	Blood pressure↓, incrementally dysfunctional myocardial performance, myocardial failure	Chang et al. (1993)
STX	Hanky albino guinea pigs	i.p	10 µg/kg	11 min	Acute	Blood pressure↓, blood pH↓	Benton et al. (1994)

↑ increased, ↓ decreased, i.c.v. intracerebroventricular, i.p. intraperitoneal, i.v. intravenous, ALP alkaline phosphatase, ALT alanine amino-transferase, AST aspartate amino-transferase, ATX-a anatoxin-a, CAT catalase, CYN cylindrospermopsin, GNTX guanitoxin, GSH glutathione, GPX glutathione peroxidase, GST glutathione S-transferase, LDH lactate dehydrogenase, MC microcystin, MDA malondialdehyde, SOD superoxide dismutase, STX saxitoxin. The weight of the cyanobacterial material refers to dry weight