Ochratoxin A induces cytotoxicity, DNA damage and apoptosis in rat hepatocyte primary cell culture at nanomolar concentration

摘要

Ochratoxin A (OTA), a mycotoxin produced by several species of Aspergillus and Penicillum, is widely found as a contaminant of food. OTA exhibits a wide range of toxic activities, including nephro- and hepatotoxicity. Although the mechanisms of its genotoxicity and carcinogenicity have been studied before, many controversial results have been published. In addition, the studies were mostly conducted with kidney cells. Therefore, the present study used a primary culture of Wistar rat hepatocytes incubated with increasing concentrations of OTA (2.0-6.0 nanomolar). OTA treatment showed dose-dependent cytotoxicity and DNA damage. Further, flow cytometric analysis of hepatocytes showed dose-dependent apoptosis, suggesting that OTA-induced hepatotoxicity is, may be partly, mediated by apoptosis. Vascular endothelial growth factor gene, a potent pro-angiogenic in hepatocellular carcinoma and responsible for hepatocyte regeneration, did not show any change with OTA treatment, as analysed by reverse transcription polymerase chain reaction. Thus, the present data indicated OTA-induced rat hepatotoxicity in vitro at nanomolar concentration, which inferred a major possible target other than kidney cells