Critical role of reactive oxygen species formation in microcystin-induced cytoskeleton disruption in primary cultured hepatocytes

Cyanobacteria (blue-green algae) -contaminated water is a worldwide public health problem. Microcystins are a group of liver-specific toxins generated by cyanobacteria. It is generally believed that the protein phosphorylatio n that leads to the disruption of intermediate filaments plays an important role in microcystin-induced hepatotoxicity. However, the mechanisms that c ontribute to the microcystin-induced alterations of microtubules and microf ilaments are not fully understood. In the present study, the effects of mic rocystin-LR (M-LR), the most common microcystin, were examined on the organ ization of cellular microtubules and microfilaments in primary cultured rat hepatocytes, Our results indicate that M-LR initiated reactive oxygen spec ies (ROS) formation followed by altering the cytoskeleton structures, which eventually led to significant LDH leakage. These effects were completely p revented by TEMPOL, a superoxide dismutase mimic, and also partially preven ted by desferoxamine, These findings provide further evidence that ROS form ation, especially superoxide radical, plays a crucial role in M-LR-induced disruption of cytoskeleton organization and consequent hepatotoxicity.