Characterization of Microcystin-Induced Dualistic Toxic Effects on Primary Rat Hepatocytes.

Microcystins (MCs) comprise a group of widely characterized cyclic heptapeptides able to induce a series of liver injuries, including acute liver failure and primary liver cancer. Although the dualistic effects of MCs have been postulated, the specific action mode according to the exposure dosage of MCs remains unknown. In the present study, primarily cultured rat hepatocytes were used to systematically investigate hepatotoxic characteristics of MC-LR (one of the most abundant and toxic MCs variants). Results showed that the dualistic toxicity of MC-LR on hepatocytes is dose dependent. Specifically, MC-LR at a high dose (>10-8 mol/L) induced a significant reduction in cell viability, whereas low-dose MC-LR (<10-8 mol/L) was observed to promote cell proliferation. Oxidative stress measurements showed that reactive oxygen species (ROS) levels undergo a massive and rapid increase in high-dose MC-LR-treated hepatocytes and a mild and slow increase in low-dose MC-LR-treated hepatocytes. These in vitro data suggest that MC-LR is able to exert dualistic toxic effects on hepatocytes through the "two-faced" character of ROS, which causes cell death or even necrosis at high concentrations and promotes cell proliferation exclusively at low or transient concentrations.