Table 4.

Summary of nephrotoxicity of microcystins in mammalian studies in vitro.

Test Organism/System	Toxicant	Concentration/Dose	Time Point	Toxic Effects	References
Rat kidney epithelial cells (ATCC 1571)	MC-LR	13.3 μM	24 h	Apoptosis↑, ultrastructural damage	Khan et al. [96]
Rat NRK cell	MC-LR	10, 100, 1000 nM	4, 6, 7, 8 h	Bax↑	Chen et al. [97]
Isolated rat kidney	MC-LR	1 μg/L	2 h	Urine flow↑, perfusion pressure↑, glomerular filtration rate↑, sodium tubule transport fraction↓, microstructural damage	Nobre et al. [98]
Vero-E6 cell	MC-LR, cyanobacterial crude extracts	1.4–175 nM	24, 48, 72 h	Cell viability↓	Dias et al. [99]
Vero-E6 cell	MC-LR, cyanobacterial crude extracts	5, 50, 500, 5000 nM	24 h	Cell proliferation↑, P38↑, JNK↑, ERK1/2 activity↑	Dias et al. [40]
Vero-E6 cell	MC-LR	1.3, 2.5, 5, 10, 20, 30, 40, 50, 75, 100, 150 μM	24, 48, 72 h	Cell viability↓, autophagy, apoptosis, necrosis, ultrastructural damage	Alverca et al. [100]
Vero-E6 cell	MC-LR	6, 12, 25, 50 μM	24 h	Cell viability↓, autophagy, cytoskeleton disruption↑	Menezes et al. [101]
HEK293	MC-LR, MC-RR, MC-LW, MC- LF	0.01, 0.1, 1, 10, 100, 1000 nM	4 h	Cell viability↓, phosphatase activity↓, modulation of Oatps expression	Fischer et al. [54]
HEK293	MC-LR	2, 10 μM	24 h	Ceramide↑, PP2A activity↑, cytoskeleton disruption↑	Li et al. [102]
HEK293	MC-LR	10 μM	24 h	PP2A activity↓, alteration of c-myc expression	Fan et al. [41]