Mitigating effect of paxilline against injury produced by Cd2+ in rat pheochromocytoma PC12 and ascites hepatoma AS-30D cells

On two rat cell lines, pheochromocytoma PC12 and ascites hepatoma AS-30D, and on rat liver mitochondria we studied action of paxilline (lipophilic mycotoxin from fungus Penicillium paxilli which is blocker of large-conductance potassium channels) against harmful effects of Cd(II) - one of the most dangerous toxic metals and environmental pollutants. We investigated an influence of paxilline on cell viability and mitochondrial function in the presence and in the absence of Cd2+. As found, paxilline protected partially from the Cd2+-induced cytotoxicity, namely taken in concentration of 1 μM it decreased the Cd2+-induced cell necrosis in average by 10–14 or 13–23% for AS-30D and PC12 cells, respectively. Nevertheless, paxilline did not affect the Cd2+-induced apoptosis of AS-30D cells. The alleviating concentration of paxilline reduced an intracellular production of reactive oxygen species (ROS) in PC12 cells intoxicated by Cd2+ and enhanced the ROS production in control AS-30D cells; however, it weakly affected mitochondrial membrane potential of the cells in the absence and in the presence of Cd2+. The ameliorative concentration of paxilline decreased the maximal respiration rates of control cells of both types after short-term (3–5 h) treatment with it while the rates reached their control levels after long-term (24–48 h) incubation with the drug. Paxilline was not protective against the Cd2+-induced membrane permeability and respiration rate changes in isolated rat liver mitochondria. As result, the mitochondrial electron transport chain was concluded to contribute in the mitigating effect of paxilline against the Cd2+-produced cell injury. •Paxilline attenuated Cd2+-produced toxic effects.•Paxilline decreased Cd2+-induced necrosis of both AS-30D and PC12 cells.•Paxilline reduced ROS formation in PC12 cells treated by Cd2+ and enhanced it in untreated AS-30D cells.•Paxilline produced reversible decline of mitoETC activity that was the early cellular effect of the drug.•mitoETC was proposed to contribute in the protective action of paxilline.