Valproic Acid Modulates Superoxide Dismutase, Uric Acid-Independent FRAP and Zinc in Blood of Adult Epileptic Patients

Abstract

We aimed to evaluate changes in antioxidant status in blood during valproate (VPA) monotherapy of adult patients with epilepsy. Antioxidant enzymes [plasma superoxide dismutase (pSOD), erythrocyte superoxide dismutase (eSOD)] and non-enzymatic indices [concentration of trace elements in serum: selenium, copper, zinc (sZn) and uric acid (UA), as well as the ferric reducing ability of plasma (FRAP) and UA-independent FRAP (UAiFRAP)] were evaluated in 21 adult patients with epilepsy and 21 healthy controls. Significant differences between the study group and controls were found for pSOD (p = 0.002) and UAiFRAP (p = 0.003). pSOD was higher, whilst UAiFRAP was lower in patients compared to controls. The activity of eSOD was higher in patients treated with VPA for a longer period (7-14 years) in comparison to controls (p = 0.001) and patients with a short period of VPA treatment (p < 0.001). Patients with uncontrolled epilepsy exhibited higher sZn than seizure-free patients (p = 0.041). Standard diet and moderate use of alcohol and/or nicotine did not exert significant effects on redox balance. We conclude that the antioxidant status of epileptic patients is modified by valproate monotherapy. The frequency of seizures and duration of VPA therapy are associated with changes of oxidative/antioxidative balance. The most sensitive and relevant parameters for antioxidative defence mechanism are pSOD, UAiFRAP and sZn.

Investigation of the Effects of Edaravone on Valproic Acid Induced Tissue Damage in Pancreas

“…Therefore, administration of VPA induced suppressing activity on the immune system and antioxidant enzymes that may contribute to the development of organ toxicity and dysfunction (34). Płonka-Półtorak et al (35) found higher SOD activities in plasma and erythrocyte of patients treated with VPA. Whereas, Vidya and Subramanian (36) found decreased activities of antioxidant enzymes such as SOD, GPx and CAT in the liver and kidney tissues of rats treated with sodium valproate.…”

Copper and Zinc, Biological Role and Significance of Copper/Zinc Imbalance

“…The antioxidant status of epileptic patients was modified by valproate monotherapy. The frequency of seizures and duration of VPA therapy were associated with changes of oxidative/antioxidative balance [224].…”

Trace Elements, Antioxidant Enzymes and Free Carnitine Levels Among Epileptic Patients Treated with Valproate Monotherapy

“…An involvement of lipid peroxidation seems to be probable and the elevated activity of pSOD in some studies may be explained by this induction. Significant effects of duration of VPA therapy, activity of seizures and gender were found on Zn, pSOD, and erythrocyte SOD (eSOD) levels [4,9]. Also in prospective studies [18,19] were reported increased levels of eSOD in epileptic children after implementation of VPA treatment.…”

“…20% [27]. In numerous studies, reduced carnitine levels were found during VPA therapy, especially with prolonged use and with high dosage levels [29]. The mechanism of this may include: 1) the formation of valproylcarnitine, 2) the reduction of tubular reabsorption of carnitine in the kidneys, 3) the inhibition of selected enzymes, which take part in biosynthesis of carnitine, 4) the inhibition of the membrane carnitine transporter and 5) the impairment of recycling of carnitine from long-chain acylcarnitines by the VPA-induced decrease of mitochondrial free Co-A level.…”

“…In numerous studies there was found to be an imbalance in oxidative status of the patient with epilepsy treated with VPA [9].…”