Stimulation of lipid peroxidation increases the intracellular calcium content of isolated hepatocytes

Lipid peroxidation induced in isolated rat hepatocytes by FeCl₃ (0.1 mM) was associated with an increase in the cytosolic free Ca²⁺ and in the ionophore-mobilizable Ca²⁺ content o both mitochondrial and extramitochondrial (endoplasmic reticular) pools. Ca²⁺ accumulation was completely prevented by the antioxidants promethazine and vitamin E succinate and was not linked to the inhibition of plasma membrane (Ca²⁺+Mg²⁺)-ATPase and Ca²⁺ transport or to the depletion of intracellular ATP content. Moreover, preincubation of the hepatocytes with the Ca²⁺ channel blockers verapamil and nifedipine inhibited the elevation of cytosolic Ca²⁺, as well as the ion accumulation without interfering with the stimulation of lipid peroxidation by iron. These results suggest that peroxidative alterations of the hepatocyte plasma membranes might perturb the functions of verapamil- and nifedipine-sensitive Ca²⁺ channels resulting in a net influx of Ca²⁺, which is subsequently sequestrated in the intracellular compartments.