Hepatic ultrastructural changes induced by the toxin microcystin-LR (MCLR) in mice

Microcystin-LR (MCLR) is a cyclic heptapeptide produced by the blue-green algae Microcystis aeruginosa. It is highly toxic and causes death in rodents due to hypovolemic shock with associated intrahepatic hemorrhage. The molecular mechanism of toxicity is unknown. In order to provide additional information regarding the toxicity of MCLR, the ultrastructural changes present in livers of mice following the administration of 100 micrograms MCLR/kg intraperitoneally, (i.p.) were examined. Time-dependent changes were observed. Disruption of cell to cell contact occurred with infiltration of erythrocytes 60 min after MCLR treatment. Hepatocyte distortion, mitochondrial aggregation, and the prominent accumulation of large areas of endoplasmic reticulum were observed. No detectable hepatic changes in sinusoidal endothelial cells were present. The results suggest that MCLR preferentially affects hepatocytes, although the observations do not preclude the involvement of hepatic vasculature in the toxicity of MCLR.