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.

Cd(2+)-induced mitochondrial dysfunction-mediated cytotoxicity; Large-conductance potassium channel blocker; Mitochondrial electron transport chain; Paxilline; Protection mechanism(s); Rat liver mitochondria and PC12 and AS-30D cells.