Cylindrospermopsin

Cylindrospermopsin, a cyanotoxin, is a polycyclic uracil derivative containing guanidine and sulfate groups, which can inhibit protein synthesis and covalently modify DNA or RNA. Cylindrospermopsin induces hepatocellular hypertrophy, renal cellular hypertrophy, intracellular reactive oxygen species (ROS), DNA strand breaks, mitochondrial hyperpolarisation, ultrastructural damage, and altered gene expression in liver, kidney, and intestinal cells. Cylindrospermopsin can be used in research including hepatocellular carcinoma and water quality testing^[1][2][3][4]. In Vitro:Cylindrospermopsin induces micronucleus formation and whole chromosome loss in transformed human lymphoblastoid cells in vitro, indicating mutagenicity^[2].
Cylindrospermopsin (0.3-40 μg/mL; 24-48 h) induces concentration- and time-dependent cytotoxicity in Caco-2 cells, with MTS reduction being the most sensitive endpoint (EC₅₀ of 2.5 μg/mL at 24 h and 0.6 μg/mL at 48 h)^[3].
Cylindrospermopsin (0.625-2.5 μg/mL; 24 h) modulates oxidative stress markers in Caco-2 cells, increasing ROS at 1.25 μg/mL and GCS activity and GSH content at 2.5 μg/mL after 24 h exposure^[3].
Cylindrospermopsin (0.625-2.5 μg/mL; 24-48 h) induces ultrastructural morphological alterations in Caco-2 cells at both 0.625 μg/mL and 2.5 μg/mL after 24 h and 48 h exposure, including nucleolar segregation, mitochondrial damage, and lipid degeneration^[3].
Cylindrospermopsin (0.05-0.5 μg/mL; up to 5 h) induces dose- and time-dependent intracellular ROS formation in HepG2 cells, with a ~5-fold increase at 0.5 μg/mL after 5 h of exposure^[4].
Cylindrospermopsin (0.125-0.5 μg/mL; 4, 12, 24 h) induces non-oxidative DNA strand breaks in HepG2 cells at 0.25 and 0.5 μg/mL after 12 and 24 h of exposure, with no oxidative DNA damage detected^[4].
Cylindrospermopsin (0.125-0.5 μg/mL; 12, 24 h) does not induce apoptosis or increase cell death in HepG2 cells at concentrations up to 0.5 μg/mL after 12 or 24 h of exposure^[4].
Cylindrospermopsin (0.25-0.5 μg/mL; 12, 24 h) induces mitochondrial membrane hyperpolarization in HepG2 cells at 0.25 and 0.5 μg/mL after 12 h, and at 0.5 μg/mL after 24 h of exposure^[4]. In Vivo:Cylindrospermopsin (75-300 μg/kg/d; p.o.; daily; 90 days) induces dose-dependent hepatic and renal toxicity in CD-1 mice, with males more sensitive to renal end points, and no observed adverse effect level identifiable at any tested dose^[1].
Cylindrospermopsin (500-1500 mg/kg; p.o.; 1-3 doses separated by 2 weeks) shows potential tumour initiation activity in mice, with a relative risk of 6.2 for neoplastic processes^[2].