8-hydroxy-2--deoxyguanosine and Epilepsy

The relationship between anti-epileptic usage and oxidative damage has not yet been clearly understood. In our study, we investigated oxidative stress parameters, carnitine levels, liver function tests (LFT) and their relationship in epileptic children treated with valproic acid or levetiracetam.. LFTs, serum free carnitine and oxidative damage markers and their relations with each other were determined in patients who are on valproic acid or levetiracetam treatment at least for 6 months. 25 patients on therapeutic doses of valproic acid, 26 patients on therapeutic doses of levetiracetam and 26 healthy volunteers as controls were included. LFTs, ammonia, carnitine, lipid peroxidation biomarker malondialdehyde (MDA) and a sensitive marker of DNA damage, 8-hydroxy-2-deoxyguanosine (8-OHdG) levels were measured. Results of patients are compared to healthy controls. The data is evaluated with IBM SPSS Statistics 22.0.. Ammonia and MDA levels were elevated in patients using levetiracetam; 8-OHdG levels were elevated in both patient groups. Carnitine levels were significantly low in patients under valproic acid therapy, however they were not found to be correlated with MDA, 8-OHdG or LFTs. MDA showed positive correlation with ammonia and 8-OHdG in the levetiracetam group.. We did not observe hepatotoxicity in patients under therapeutic doses of valproic acid. However, epileptic children under therapeutic doses of levetiracetam showed significantly elevated levels of MDA and 8-OHdG, which is supportive for oxidative damage under levetiracetam therapy. This result was observed for the first time in childhood epilepsies and further studies are needed to understand its mechanism.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Anticonvulsants; Carnitine; Child; Deoxyguanosine; Epilepsy; Female; Humans; Levetiracetam; Lipid Peroxidation; Liver; Liver Function Tests; Male; Malondialdehyde; Retrospective Studies; Thiobarbituric Acid Reactive Substances; Valproic Acid

Excitotoxic stress has been associated with several different neurological disorders, and it is one of the main causes of neuronal degeneration and death. To identify new potential proteins that could represent key factors in excitotoxic stress and to study the relationship between polyamine catabolism and excitotoxic damage, a novel transgenic mouse line overexpressing spermine oxidase enzyme in the neocortex (Dach-SMOX) has been engineered. These transgenic mice are more susceptible to excitotoxic injury and display a higher oxidative stress, highlighted by 8-Oxo-2'-deoxyguanosine increase and activation of defense mechanisms, as demonstrated by the increase of nuclear factor erythroid 2-related factor 2 (Nrf-2) in the nucleus. In Dach-SMOX astrocytes and neurons, an alteration of the phosphorylated and non-phosphorylated subunits of glutamate receptors increases the kainic acid response in these mice. Moreover, a decrease in excitatory amino acid transporters and an increase in the system x

Topics: 8-Hydroxy-2'-Deoxyguanosine; Amino Acid Transport System y+; Animals; Behavior, Animal; Brain; Deoxyguanosine; Epilepsy; Excitatory Amino Acid Transporter 1; Excitatory Amino Acid Transporter 2; Glutamic Acid; Mice, Transgenic; Models, Biological; Neuroglia; Neurotoxins; NF-E2-Related Factor 2; Oxidoreductases Acting on CH-NH Group Donors; Polyamine Oxidase; Protein Subunits; Protein Transport; Receptors, AMPA; Sulfasalazine; Synaptosomes

The aim of our research was to evaluate some biochemical changes in blood during lamotrigine (LTG) monotherapy of adult patients with epilepsy, and to check possible associations between typical selenium status parameters and the frequency of seizures.. The study was performed by examining aspartate aminotransferase (AspAT), alanine aminotransferase (AlaAT), creatinine, ferric reducing ability of plasma (FRAP), serum uric acid (UA), uric-acid-independent FRAP (UAiFRAP), plasma glutathione peroxidase (GPX3), selenoprotein P (SelP), plasma superoxide dismutase (pSOD), 8-hydroxy-2'-deoxyguanosine (8-OHdG) in serum and urine, serum selenium (sSe) and zinc (sZn), in 22 adult patients with epilepsy and 22 healthy controls. Additionally, the levels of LTG were determined in patients.. pSOD activity was higher in the study group (5.32±1.24 U/ml) compared with the controls (4.05±0.92 U/ml, p=0.008). No other statistical difference between patients and controls was found.. Lack of difference in parameters other than SOD, particularly no difference in 8-OHdG concentrations between the patients treated with LTG compared to the control subjects suggests that these patients are at no particular risk of oxidative DNA damage. In patients who are well or moderately well clinically controlled, selenium status parameters (sSe, GPX3, SelP) are not directly connected with the frequency of seizures.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Anticonvulsants; Antioxidants; Case-Control Studies; Deoxyguanosine; Epilepsy; Female; Humans; Lamotrigine; Male; Selenium; Superoxide Dismutase; Triazines; Young Adult

Mixed natural antioxidants can be combined in a prophylactic food against age related disease involving reactive oxygen species. beta-Catechin is an antioxidant drink, having free radical scavenging activities. It contains green tea extract as a main component as well as ascorbic acid, sunflower seed extract, dunaliella carotene and natural vitamin E. In the present study, we examined the effect of beta-catechin on lipid peroxide formation and superoxide dismutase (SOD) activity in aged rat brain and the effect on 8-hydroxy-2'-deoxyguanosine (8-OHdG) in ipsilateral cortex, 30 min after ferric chloride solution was injected into the left cortex of rats. beta-Catechin solution was orally administered to aged rats and normal rats for 1 month. One-month administration of beta-catechin solution increased SOD activity in the mitochondria fraction of striatum and midbrain and decreased thiobarbiturate reactive substance formation in the cortex and cerebellum of aged rats. It also inhibited 8-OHdG formation in the ipsilateral cortex 30 min after injection of ferric chloride solution. These results suggest that beta-catechin is a suitable prophylactic beverage against age-related neurological diseases associated with reactive oxygen species.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aging; Animals; Antioxidants; Brain; Catechin; Cerebellum; Cerebral Cortex; Corpus Striatum; Deoxyguanosine; DNA Damage; Epilepsy; Hippocampus; Hypothalamus; Iron; Lipid Peroxides; Male; Medulla Oblongata; Mesencephalon; Rats; Rats, Wistar; Superoxide Dismutase; Thiobarbituric Acid Reactive Substances

To examine the change of 8-hydroxy-2'deoxyguanosine (8-OHdG) levels, which are used as a marker for oxidative DNA damage, in iron-induced epileptogenic foci of the rat cerebrum.. Male Wistar rats were given a cortical injection of ferric chloride, and their 8-OHdG levels were determined over time. Additional animals were pretreated with the antiepileptic drug zonisamide (ZNS) before the ferric chloride injection, and their 8-OHdG levels were compared with the nonpretreated rats.. Fifteen minutes after ferric chloride solution injection, the level of 8-OHdG increased, reaching a maximum 30 minutes after injection. Sixty minutes after injection, the levels coincided with those of controls. ZNS, in concentrations of 50 and 100 mg/kg body weight, prevented the increase of 8-OHdG levels within the cerebrum 30 minutes after iron solution injection.. These results indicate that the formation of iron-induced epileptogenic foci in rats is related to DNA-damage-induced reactive oxygen species and that the inhibition of 8-OHdG formation by ZNS after iron injection may be due to the drug's antioxidant activity. The data suggest that free radical species known to be formed during iron salts-induced focal epileptogenesis cause damage to isocortical DNA. Furthermore, ZNS appears to inhibit the focal injuring response to DNA that occurs following iron salts-induced acute epileptogenesis.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Anticonvulsants; Brain Chemistry; Cerebral Cortex; Chlorides; Deoxyguanosine; DNA Damage; Epilepsy; Ferric Compounds; Isoxazoles; Male; Oxidative Stress; Rats; Rats, Wistar; Reactive Oxygen Species; Zonisamide

The objective of this study was to determine the role of mitochondrial superoxide radical-mediated oxidative damage in seizure-induced neuronal death. Using aconitase inactivation as an index of superoxide production, we found that systemic administration of kainate in rats increased mitochondrial superoxide production in the hippocampus at times preceding neuronal death. 8-Hydroxy-2-deoxyguanosine, an oxidative lesion of DNA, was also increased in the rat hippocampus following kainate administration. Manganese(III) tetrakis(4-benzoic acid)porphyrin, a catalytic antioxidant, inhibited kainate-induced mitochondrial superoxide production, 8-hydroxy-2-deoxyguanosine formation and neuronal loss in the rat hippocampus. Kainate-induced increases of mitochondrial superoxide production and hippocampal neuronal loss were attenuated in transgenic mice overexpressing mitochondrial superoxide dismutase-2. We propose that these results demonstrate a role for mitochondrial superoxide production in hippocampal pathology produced by kainate seizures.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aconitate Hydratase; Animals; Cell Death; Deoxyguanosine; DNA Damage; Epilepsy; Free Radical Scavengers; Hippocampus; Kainic Acid; Male; Metalloporphyrins; Mitochondria; Neurons; Neuroprotective Agents; Neurotoxins; Oxidative Stress; Rats; Rats, Sprague-Dawley; Seizures; Superoxide Dismutase; Superoxides