The anticonvulsants gabapentin (GBP), carbamazepine (CBZ), lamotrigine (LTG) and oxcarbazepine (OXC) are commonly used in the treatment of epilepsy, but the precise molecular mechanisms of action of these antiepilptic drugs are still largely unknown. Astrocytes provide a vital protective function in the brain. Because astrocytes regulate extracellular glutamate levels, the aim of this investigation was to characterize the effects of in vitro AED exposure on glutamine synthase. Glutamine synthase {GS) is an inducible enzyme present in astrocytes. It is considered to be a marker of astrocyte maturation and is expressed both in vivo and in vitro. GS is a highy regulated protein, very sensitive to oxidative stress. It shows increased expression and activity during maturity after astrocytic differentiation 11 ]. The purpose of this study was to determine the in vitro effects of anliconvulsants GBP, CBZ, LTG and OXC on the enzymatic activity of glutamine synthase in rat astrocytes, when the drugs were added to primary cultures of these cells at increasing dosage (1. 10. 100mg/ml culture medium). The GS activity was lower in the astrocytes treated with the various drugs, compared to the untreated control cultures (0.05 </; < 0.5). The only exception was gabapentin, which did not modify significantly the GS activity of the control (p > 0.5). All drugs, including GBP, when added to cultures pre-treated with LPS (lipopolysaccharides), used as a control stress-inducing molecule, induced a further significant decrease in GS activity, the greatest effect being observed with OXC at 100 ing/ml (/> < 0.01 ). Our experiments indicate that significant changes in GS activity of differentiated ustrocytes occurred after the addition of AEDs at various concentrations. The results suggest thai GBP. CBZ, LTG. and OXC may induce functional modifications in astrocytes which affect some biochemical events in untreated or in LPStreated cells.
Glutamine synthetase activity in rat astrocytes after treatment with gabapentin, carbamazepine, lamotrigine and oxcarbazepine in vitro
CARDILE, Venera;
1999-01-01
Abstract
The anticonvulsants gabapentin (GBP), carbamazepine (CBZ), lamotrigine (LTG) and oxcarbazepine (OXC) are commonly used in the treatment of epilepsy, but the precise molecular mechanisms of action of these antiepilptic drugs are still largely unknown. Astrocytes provide a vital protective function in the brain. Because astrocytes regulate extracellular glutamate levels, the aim of this investigation was to characterize the effects of in vitro AED exposure on glutamine synthase. Glutamine synthase {GS) is an inducible enzyme present in astrocytes. It is considered to be a marker of astrocyte maturation and is expressed both in vivo and in vitro. GS is a highy regulated protein, very sensitive to oxidative stress. It shows increased expression and activity during maturity after astrocytic differentiation 11 ]. The purpose of this study was to determine the in vitro effects of anliconvulsants GBP, CBZ, LTG and OXC on the enzymatic activity of glutamine synthase in rat astrocytes, when the drugs were added to primary cultures of these cells at increasing dosage (1. 10. 100mg/ml culture medium). The GS activity was lower in the astrocytes treated with the various drugs, compared to the untreated control cultures (0.05 0.5). All drugs, including GBP, when added to cultures pre-treated with LPS (lipopolysaccharides), used as a control stress-inducing molecule, induced a further significant decrease in GS activity, the greatest effect being observed with OXC at 100 ing/ml (/> < 0.01 ). Our experiments indicate that significant changes in GS activity of differentiated ustrocytes occurred after the addition of AEDs at various concentrations. The results suggest thai GBP. CBZ, LTG. and OXC may induce functional modifications in astrocytes which affect some biochemical events in untreated or in LPStreated cells.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
