Swelling and damage of glial cells by lactacidosis and glutamate: Effect of α-trinositol

Abstract

The therapeutical efficacy of α-trinositol (D-myo-inositol-1,2,6- trisphosphate), an isomer of the intracellular messenger IP3, was analyzed on cytotoxic swelling and damage of glial cells in vitro from lactacidosis or glutamate. C6 glioma cells suspended in a physiological medium were either exposed to pH 5.0 by administration of lactic acid, or to 1 mM glutamate. Cell swelling and viability were quantified by flow cytometry. Lactacidosis of pH 5.0 led to an increase in cell volume to 139.7 ± 1.3% within 20 min whereas α-trinositol was reducing the swelling response by approximately 25% (P < 0.01). In addition, at pH 5.0 the fraction of viable cells was lowered from 94.3 ± 0.2% (control) to only 53.8 ± 3.1% after 60 min. α-Trinositol was found to protect also cell viability; at 60 min of lactacidosis 70.2 ± 1.6% of the cells still were viable (P < 0.01). The addition of glutamate (1 mM) to the cell suspension led to a steady increase in cell size, reaching 110% of control at 120 min, irrespectively of whether α-trinositol was added or not.