Effects of Valproate, Carbamazepine, and Levetiracetam on the Antioxidant and Oxidant Systems in Epileptic Patients and Their Clinical Importance

Varoğlu, Asuman Orhan; Yıldırım, Abdülkadir; Aygül, Recep; Gündoğdu, Ömer Lütfi; Şahin, Yusuf

doi:10.1097/wnf.0b013e3181d1e133

Cited by 53 publications

(41 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Lower TAC [86] and GSH [98] in plasma, and GPX and CAT in erythrocytes were also observed [92]. In accordance with its pro-oxidative action, decreased SOD [92] and increased 8-OHdG [96] and nitrite/nitrate in erythrocytes were also observed. However, there are also studies which do not confirm CBZ pro-oxidative action [83, 86, 91, 95] and even studies with anti-oxidative action [88, 93, 99].…”

Section: Antiepileptic Drug Therapy and Oxidative Stressmentioning

confidence: 91%

“…Erythrocyte GPX [91, 92], GR [93] and serum Se [94], uric acid and albumin [80], which are considered endogenous enzymatic and non-enzymatic antioxidant molecules, were found to be reduced in children and adults treated with VPA. Furthermore, in studies in patients with epilepsy, treated with VPA, increased levels of oxidative macromolecular damage markers, such as MDA [76, 86, 90, 91] and 15F-2t-isoP [95], which are markers of enhanced lipid peroxidation and increased levels of 8-OHdG [90, 96], which is a marker of nucleic acid damage, were observed. Similarly, enhanced lipid peroxidation [80] and decreased SOD and GPX [92] was seen in studies with phenobarbital.…”

Section: Antiepileptic Drug Therapy and Oxidative Stressmentioning

confidence: 99%

See 1 more Smart Citation

The Role of Reactive Species in Epileptogenesis and Influence of Antiepileptic Drug Therapy on Oxidative Stress

Martinc

Grabnar²,

Vovk³

2012

Current Neuropharmacology

View full text Add to dashboard Cite

Epilepsy is considered one of the most common neurological disorders. The focus of this review is the acquired form of epilepsy, with the development process consisting of three major phases, the acute injury phase, the latency epileptogenesis phase, and the phase of spontaneous recurrent seizures. Nowadays, an increasing attention is paid to the possible interrelationship between oxidative stress resulting in disturbance of physiological signalling roles of calcium and free radicals in neuronal cells and mitochondrial dysfunction, cell damage, and epilepsy. The positive stimulation of mitochondrial calcium signals by reactive oxygen species and increased reactive oxygen species generation resulting from increased mitochondrial calcium can lead to a positive feedback loop. We propose that calcium can pose both, physiological and pathological effects of mitochondrial function, which can lead in neuronal cell death and consequent epileptic seizures. Various antiepileptic drugs may impair the endogenous antioxidative ability to prevent oxidative stress. Therefore, some antiepileptic drugs, especially from the older generation, may trigger oxygen-dependent tissue injury. The prooxidative effects of these antiepileptic drugs might lead to enhancement of seizure activity, resulting in loss of their efficacy or apparent functional tolerance and undesired adverse effects. Additionally, various reactive metabolites of antiepileptic drugs are capable of covalent binding to macromolecules which may lead to deterioration of the epileptic seizures and systemic toxicity. Since neuronal loss seems to be one of the major neurobiological abnormalities in the epileptic brain, the ability of antioxidants to attenuate seizure generation and the accompanying changes in oxidative burden, further support an important role of antioxidants as having a putative antiepileptic potential.

show abstract

Section: Antiepileptic Drug Therapy and Oxidative Stressmentioning

confidence: 91%

Section: Antiepileptic Drug Therapy and Oxidative Stressmentioning

confidence: 99%

The Role of Reactive Species in Epileptogenesis and Influence of Antiepileptic Drug Therapy on Oxidative Stress

Martinc

Grabnar²,

Vovk³

2012

Current Neuropharmacology

View full text Add to dashboard Cite

show abstract

“…Studies on the effect of AEDs on prooxidative/antioxidant balance in patients with epilepsy have, so far, mainly focused on valproic acid and carbamazepine treatments and their effect on the lipid peroxidation process and antioxidant defense mechanisms (1,11,22,23). Interestingly, the extent of protein oxidative damage has not been evaluated, while DNA oxidative damage has only been examined in children receiving valproic acid therapy and recently, in one study, on adult patients receiving valproic acid, carbamazepine and levetiracetam (16,24). Furthermore, data on lamotrigine effects on oxidative stress in patients with epilepsy are scarce.…”

Section: Introductionmentioning

confidence: 99%

Antiepileptic Drugs Affect Protein, Lipid and DNA Oxidative Damage and Antioxidant Defense in Patients with Epilepsy

Ercegovac¹,

Jović²,

Simić³

et al. 2013

Journal of Medical Biochemistry

View full text Add to dashboard Cite

List of abbreviations: AEDs -antiepileptic drugs, 8 -epi-PGF 2a -urinary isoprostanes, GPX -glutathione peroxidase, ILAE -International League Against Epilepsy, 8-OHdG -8-hydroxy-2'-deoxyguanosine, P-SH -protein thiol groups, RCD -reactive carbonyl derivatives, ROS -reactive oxygen species, SOD -superoxide dismutase. SummaryBackground: To get more insight into the effects of the most widely used antiepileptic drugs (AEDs) on the pro oxi dant/ antioxidant balance in epi lep sy, a comparative analysis of the byproducts of oxidative damage and antioxidant de fense mechanisms was performed in patients with epilepsy treated with la mo trigine, carbamazepine and valproic acid. Methods: Byproducts of oxidative damage to proteins (reactive carbonyl derivatives, RCD and protein thiol groups, P-SH), lipids (urinary isoprostanes, 8 -epi-PGF 2a ) and DNA (urinary 8-hydroxy-2'-deoxyguanosine, 8-OHdG), as well as the activities of antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPX) were measured in 60 patients with newly diagnosed seizure (at illness onset and after 6 months of treatment with lamotrigine, carbamazepine or valproic acid) and in 20 healthy controls. Results: In patients with epilepsy, RCD, urinary 8-epi-PGF 2a and 8 -OHdG, together with SOD and GPX activities were significantly increased, while P-SH were only slightly decreased. After 6 months of treatment with AEDs, a decrease was observed in RCD, urinary 8-epi-PGF 2a and 8-

show abstract

“…*P \ 0.05 the oxidative stress system of epilepsy patients [31][32][33], leading to increased risk of atherosclerosis in children and adults who are taking antiepileptic treatment [14,15]. In epileptic children who are treated with AEDs, there is an increase in the oxidative modification of low-density lipoprotein cholesterol (LDL-C), an important factor responsible for atherosclerosis [34,35]. Varoglu et al (2010) reported significantly lower serum paraoxonase and ARE activities of PON1, an antioxidant enzyme with three activities of paraoxonase (PON1), ARE, and dyazoxonase that can destroy active lipids in mildly oxidized LDL-C (ox-LDL) and, thus, prevent the induction of inflammatory response [36].…”

Section: Discussionmentioning

confidence: 99%

The Effects of Levetiracetam on Cerebrospinal Fluid and Plasma NPY and GAL, and on the Components of Stress Response System, hs-CRP, and S100B Protein in Serum of Patients with Refractory Epilepsy

Chen

Tan

et al. 2015

Cell Biochem Biophys

View full text Add to dashboard Cite

Our objective is to explore the effects of levetiracetam on the levels of neuropeptides, serum activity and concentrations of oxidative stress and inflammatory response proteins, and levels of brain injury marker in patients with refractory epilepsy. Seventy-two patients with refractory epilepsy received levetiracetam treatment. Neuropeptides galanin (GAL) and neuropeptide Y (NPY) in plasma and cerebrospinal fluid (CSF) were detected using double-antibody sandwich immunoassay and radioimmunoassay, respectively. Enzyme-linked immunosorbent assay was used to detect serum activity of paraoxonase (PON1) and serum concentrations of oxidized low-density lipoprotein (ox-LDL) and S100B. Arylesterase (ARE) activity was measured by colorimetric assay, and immune scatter turbidimetry was used to detect a high-sensitivity C-reactive protein (hs-CRP). After treatment, NPY and GAL in plasma and CSF of the patients were significantly decreased as compared to concentrations before treatment (P < 0.05). Levetiracetam reduced serum activities of PON1 and ARE (P < 0.05) and led to markedly increased serum levels of ox-LDL (P < 0.05). Serum concentrations of hs-CRP and S100B protein were significantly lower after levetiracetam administrations than before treatment (P < 0.05). Levetiracetam treatment had a clear beneficial effect on the overall quality of life (QOL) scores of the patients, as indicated by significantly improved cognitive functioning, behavior problems, emotional conditioning, physical condition, social functioning, self-assessed life quality score, self-assessed health score, and the total QOL score (P < 0.05). Levetiracetam can improve life quality of patients with refractory epilepsy, decrease NPY and GAL in plasma and cerebrospinal fluid, serum PON1 and ARE activities, and serum levels of ox-LDL, hs-CRP, and S100B. Levetiracetam therefore may be considered a drug of choice for treating refractory epilepsy.

show abstract

Effects of Valproate, Carbamazepine, and Levetiracetam on the Antioxidant and Oxidant Systems in Epileptic Patients and Their Clinical Importance

Cited by 53 publications

References 13 publications

The Role of Reactive Species in Epileptogenesis and Influence of Antiepileptic Drug Therapy on Oxidative Stress

The Role of Reactive Species in Epileptogenesis and Influence of Antiepileptic Drug Therapy on Oxidative Stress

Antiepileptic Drugs Affect Protein, Lipid and DNA Oxidative Damage and Antioxidant Defense in Patients with Epilepsy

The Effects of Levetiracetam on Cerebrospinal Fluid and Plasma NPY and GAL, and on the Components of Stress Response System, hs-CRP, and S100B Protein in Serum of Patients with Refractory Epilepsy

Contact Info

Product

Resources

About