Abstracts

Rationale: Oxidative stress had been implicated in the pathogenesis of diverse neurodegenerative conditions and stroke. We compared the oxidative stress status of women with epilepsy(WWE) using anti epileptic drugs (AED) with that of a control group. Methods: WWE enrolled in the Kerala Registry of Epilepsy and Pregnancy (N=79; mean age 28.3 ± 4.6 years; generalized epilepsy = 39, localization related epilepsy = 40; pregnant state = 14) and healthy women without epilepsy (N=30; mean age 25.8 ± 3.9 years; pregnant state = 10) were recruited as subjects and controls respectively. Informed consent was obtained from all. WWE were taking following AEDs: carbamazepine 29, valproate 27, phenobarbitone 17, phenytoin 9, clobazam 6, other AEDs 11. In the epilepsy group, 32 women had children with malformations and 17 women had abortion or stillbirth. The redox status was evaluated by estimating serum levels of Malondialdehyde (MDA) and Isoprostane (ISP). The activity of antioxidant enzymes superoxide dismutase (SOD), glutathione reductase (GR) catalase, total antioxidant status and glutathione content were determined in the blood by spectrophotometric methods. Results: Compared to non pregnant state, during pregnancy MDA levels (nmol/ml) were significantly elevated for the WWE (5.48 ± 1.34 vs 3.33 ± 0.91) as well as healthy controls (5.29 ± 0.67 vs 2.42 ± 0.51). The SOD levels (mg/l) were significantly lower during pregnancy for the WWE (175.8 ± 27.9 vs 135.04 ± 38.3). GR levels were significantly lower during pregnancy for healthy women (42.71 ± 9.1 vs 29.11 ± 5.7) WWE had higher levels of MDA (3.33 ± 0.91 Vs 2.42 ± 0.52) and Isoprostane (15.9 ± 4.7 Vs 10.77 ± 4.1) compared to controls. Their levels of SOD (175.81 ± 42.61 Vs 146.82 ± 42.64 ) and glutathione (1.55 ± 1.3 Vs 0.98 ± 0.98 mM) were significantly lower than those of controls. The subgroup of WWE who had infants with congenital malformation had higher levels of MDA when compared to controls (3.45 ± 0.86 Vs 2.42 ± 0.51). WWE who had abortion showed higher levels of MDA (3.41 ± 0.70 vs 2.42 ± 0.51), lower levels of SOD ( 141.91 ± 35.12 vs 175.81 ± 42.61) and glutathione (0.49 ± 0.55 vs 1.55 ± 1.3) when compared to controls. Conclusions: Pregnancy increases oxidative stress in WWE and healthy subjects. WWE exposed to AEDs had higher oxidative stress and reduced antioxidant activity. The subgroup of WWE with history of fetal malformations or abortions had higher oxidative stress and reduced antioxidant activity. Excess oxidative stress may be a final common pathway by which AEDs exert teratogenic effects.