Swelling and damage of glial cells by lactacidosis and glutamate: effect of alpha-trinositol.
The therapeutical efficacy of alpha-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 alpha-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. Alpha-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 alpha-trinositol was added or not.
Staub
F
F
Department of Neurosurgery, University of Cologne, Köln, Germany.
Peters
J
J
Plesnila
N
N
Chang
R C
RC
Baethmann
A
A
D000140:Acidosis, Lactic / Q000503:physiopathology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D048429:Cell Size / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005910:Glioma; D018698:Glutamic Acid / Q000494:pharmacology*; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D007295:Inositol Phosphates / Q000494:pharmacology*; D009457:Neuroglia / Q000187:drug effects / Q000473:pathology*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000473:pathology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007295:Inositol Phosphates; D018698:Glutamic Acid; D015544:Inositol 1,4,5-Trisphosphate; C059368:atrinositol