Glycine affects valproate hepatotoxicity.

Abstract

Valproate is a widely used anticonvulsant drug. Valproate is linked to hepatotoxicity which is rare but potentially lethal. The pathomechanism is not yet completely understood. Previous studies have shown a protective effect of glycine on this toxicity in rat hepatocytes (Vance et al., 1994). In the present study we investigated the hepatoxicity of 1-4 mM valproate in combination with glycine through absorption of neutral red from human hepatoma cells (Hep G2) in monolayer cell culture. Cell toxicity was measured by enzyme release with standard photometric test kits. In addition, a histomorphological evaluation was performed. A significant increase in the IC50 value of valproate cytotoxicity after addition of 12 mmol/l glycine was found. The average release of mitochondrial glutamate dehydrogenase as indicator of cell membrane damage decreased after addition of glycine. Cells treated with valproate in combination with 12 mmol/l glycine showed less histomorphological deformation of the nucleus and improved cell adherence. In conclusion a hepatoprotective effect of glycine on valproate-induced toxicity is also given in human hepatocytes. A nonspecific hepatoprotective effect of glycine can be assumed at least in vitro.