Biochemical variables of oxidative cell and tissue damage induced by phenytoin

The aim of our study was to evaluate a model for studying possible preventi ve effects of selective natural and synthetic antioxidants on phenytoin (PH T)-induced biochemical changes in cells (in vitro) and in organs (in vivo). We compared the cytotoxic effect of PHT on HeLa cells using one direct (ce ll number) and four indirect (Lowry MTT, NR, KB) methods. Further the adver se effect of PHT on pregnant Wistar/DV rats was studied using the activity of the lysosomal enzyme N-acetyl-beta -D-glucosaminidnse (NAGA) and the lev el of glutathione (C;SH) in maternal serum, heart and aorta, foetal Liver a nd brain, and in the placenta as markers of tissue damage. in vitro experim ents: PHT caused unbalanced growth accompanied with increased production of proteins in the cells. The activity of lysosomal enzymes and mitochondrial dehydrogenases was increased. The amount of lysosomes in the cells was als o raised. According to its cytotoxic activity, PHT can be classified as a t oxic drug as it caused 53.5% inhibition of cell proliferation in 1mM concen tration. In vivo experiments: On day 20 of gestation, PHT-induced toxic dam age (150 mg/kg) was associated with an increase in NAGA activity in materna l serum and in placenta and foetal liver. The GSH level decreased in matern al aorta, in placenta and in foetal liver. NAGA activity and GSH level in m aternal heart and in foetal brain remained unchanged. The PHT-induced bioch emical changes established in the in vitro and in vivo models used provide the possibility to assess potential preventive effects of antioxidants.