PHENYTOIN-MEDIATED OXIDATIVE STRESS IN SERUM OF FEMALE EPILEPTICS - APOSSIBLE PATHOGENESIS IN THE FETAL HYDANTOIN SYNDROME

1 The concentration of serum malondialdehyde (MDA) was measured as the index of lipid peroxidation in female epileptics with phenytoin (PHT) monotherapy. Sera from 20 female epileptics with PHT monotherapy, 12 female epileptics without anticonvulsant therapy and 20 female healthy controls were sampled. The levels of serum copper (S-Cu), serum zinc (S-Zn), copper/zinc superoxide dismutase (CuZn-SOD), and reduced gluta thione (GSH) were analyzed as interactive factors of the oxidative str ess. 2 For the female epileptics with PHF monotherapy, serum MDA conce ntration (2.6 +/- 0.7 mu M vs control 1.8 +/- 0.6 mu M, P < 0.05), CuZ n-SOD activity (178.2 +/- 63.5 U/dL vs control 97.1 +/- 36.4 U/dL, P < 0.01), and S-Cu content (126.2 +/- 36.1 mu g/dL vs control 98.4 +/- 1 6.7 mu g/dL, P < 0.05) were significantly increased, but GSH level (27 .5 +/- 6.8 mu M vs control 32.2 +/- 5.7 mu M, P < 0.05) was significan tly decreased. The level of serum MDA was associated with elevation of CuZn-SOD activity (r=0.54, P < 0.05) and S-Cu content (r=0.44, P < 0. 05) in all the samples collected from epileptics and controls. However , there were no significant differences in all the above parameters be tween the female epileptics without anticonvulsant therapy and healthy controls. 3 These results indicated that oxidative stress was enhance d in the female epileptics with PHT-monotherapy. Apart from the reacti ve PHT intermediate, the abnormal metabolism of S-Cu, CuZn-SOD, and GS H was highly involved in the PHT-mediated toxicity. Supplement of GSH, modification of CuZn-SOD enzyme activity and reduction of the absorpt ion of copper may prevent the incidence of fetal hydantoin syndrome du ring pregnancy.