dinoprost and Epilepsy

We aimed to investigate the effects of levetiracetam on oxidative stress which is one of the new antiepileptic drugs in epileptic patients.. The study consisted of 21 patients with cryptogenic partial epilepsy. We determined the urinary 15F-2t-isoprostane levels of the 30 patients which is a marker of oxidative stress. Morning urine samples were collected from the patients before beginning LEV and after 3 months treatment. Of these patients 9 were excluded from the study that had seizure history in the last 1 month. Urinary levels of 15-F2t-isoprostane determined by ELISA initially and after 3 months treatment for each patient.. Mean age of the 21 patients was 29.6, of these 11 were females and 10 males. Mean urinary 15F-2t-isoprostane level of the patients was 876 ± 447 ng/mg Cr before the treatment of LEV. After 3 months treatment the mean 15F-2t-isoprostane level of the patients was 1560 ± 630. The patients had significantly higher levels of urinary 15F-2t-isoprostane when compared with initial levels (p = 0.025).. Our results showed the increase of urinary 15F-2t-isoprostane levels in epileptic patients whom were treated with LEV which may indicate that LEV induces the oxidative stress in epileptic patients.

Topics: Adult; Anticonvulsants; Biomarkers; Dinoprost; Epilepsies, Partial; Epilepsy; Female; Humans; Isoprostanes; Levetiracetam; Male; Oxidative Stress; Piracetam

It is still an urgent need to find alternative and effective therapies to combat epileptic seizures. Tacrolimus as a potent immunosuppressant and calcineurin inhibitor is emerging as promising drug to suppress seizures. However, there are few reports applying tacrolimus to epilepsy and providing data for its antiseizure properties. In this study, we investigated the antiseizure effects of 5 and 10 mg/kg doses of tacrolimus treatment priorly to pentylenetetrazol (PTZ) induction of seizures in rats. As an experimental design, we establish two independent rat groups where we observe convulsive seizures following 70 mg/kg PTZ and sub-convulsive seizures detected by electroencephalography (EEG) following 35 mg/kg PTZ. Thereafter, we proceed with biochemical analyses of the brain including assessment of malondialdehyde level as an indicator of lipid peroxidation and detection of superoxide dismutase (SOD) enzyme activity and PGF2α. Tacrolimus pre-treatment dose-dependently resulted in lesser seizure severity according to Racine's scale, delayed start-up latency of the first myoclonic jerk and attenuated the spike percentages detected by EEG in seizure-induced rats. However, only the higher dose of tacrolimus was effective to restore lipid peroxidation. An increase in SOD activity was observed in the PTZ group, mediated by seizure activity per se, however, it was greater in the groups that received treatment with 5 and 10 mg/kg of Tacrolimus. PGF2α bursts following PTZ induction of seizures were reversed by tacrolimus pre-treatment in a dose-dependent manner as well. We report that the well-known immunosuppressant tacrolimus is a promising agent to suppress seizures. Comparative studies are necessary to determine the possible utilization of tacrolimus in clinical cases.

Topics: Animals; Anticonvulsants; Brain; Dinoprost; Disease Models, Animal; Epilepsy; Humans; Immunosuppressive Agents; Oxidative Stress; Pentylenetetrazole; Rats; Seizures; Superoxide Dismutase; Tacrolimus; Time-to-Treatment

Epilepsy is one of the most common neurological diseases. The underlying pathophysiological mechanisms in epilepsy are still unknown. Oxidative stress is believed to be one of the factors involved in the pathogenesis of epileptogenesis. In various pathophysiological conditions, reactive nitrogen species (RNS) such as nitrogen and peroxynitrite are produced and these RNSs can bind to free nucleosides and nucleotides or to nucleosides and nucleotides existing in the DNA/RNA structure. 8-Nitroguanine (8-NG) is a typical DNA nucleobase product of nitrosative damage generated by RNS. It has been proposed that F2-isoprostanes, in particular 8-iso-Prostaglandin F2α (8-isoPGF2α), are specific, reliable and non-invasive biomarkers of lipid peroxidation in vivo. In the present study, we compared the levels of lipid oxidative stress biomarker 8-isoPGF2α and nitrosative stress DNA biomarker 8-NG in patients with epilepsy undergoing antiepileptic drug (AEDs) treatment and with those in healthy participants.. The present study comprised 90 patients aged between 17 and 53 who were admitted to the Neurology Clinic of Cumhuriyet University and diagnosed with epilepsy. The patients were assigned into the intervention (n = 45) and control (n = 45) groups. Of the participants in the intervention group, 37.7% (n = 17) were treated with levetiracetam (LEV), 33.3% (n = 15) with valproic acid (VA) and 29% (n = 13) with carbamazepine. Serum 8-iso-PGF2α and 8-NG levels of the participants in the intervention and control groups were determined by ELISA.. There was no significant difference between the medication (LEV, VA, Carbamazepine) used by the participants and their 8-iso-PGF2α and 8-NG levels (p > 0.05). However, 8-iso-PGF2α and 8-NG were significantly higher in the participants in the intervention than in the participants in the control group (p < 0.001).. Our study demonstrated that there was an increase in oxidative and nitrosative stres markers in patients with epilepsy. There was no significant difference between the 8-iso-PGF2α and 8-NG levels of the participants taking three different AEDs.

Topics: Adolescent; Adult; Biomarkers; Dinoprost; Epilepsy; Female; Humans; Lipid Peroxidation; Male; Middle Aged; Nitrosative Stress; Oxidative Stress; Young Adult

To determine whether valproic acid (VPA) influences urinary levels of 15-F2t -isoprostane (15-F2t -IsoP), a marker of oxidative stress, in children.. Morning urine samples were collected from children with epilepsy receiving VPA (n = 25), carbamazepine (n = 16), or clobazam (n = 12) for > or = 4 weeks and from age-matched control subjects (n = 39). Urinary 15-F2t -IsoP levels were determined by enzyme-linked immunosorbent assay.. The mean (+/- standard deviation) urine 15-F2t -IsoP levels (nmol/mmol Cr) were: valproic acid (0.36 +/- 0.15); carbamazepine (0.24 +/- 0.10); clobazam (0.23 +/- 0.10); control group (0.20 +/- 0.09). Patients treated with VPA had significantly elevated 15-F2t -IsoP levels when compared with the control, carbamazepine, and clobazam groups (P < .05). Multiple linear regression analysis demonstrated that younger patient age and exposure to second-hand smoke were significant predictors of elevated urine 15-F2t -IsoP levels within the control group (r2 = 0.261, P = .05 and P = .01, respectively). Subjects not exposed to second-hand smoke receiving valproic acid therapy had a significantly elevated mean urine 15-F2t -IsoP level compared to subjects not exposed to second-hand smoke in the carbamazepine, clobazam and control groups (P < .05).. These data demonstrate that treatment of children with VPA is associated with higher urinary levels of 15-F2t -IsoP, a marker of oxidative stress.

Topics: Adolescent; Age Factors; Anticonvulsants; Benzodiazepines; Biomarkers; Canada; Carbamazepine; Case-Control Studies; Child; Child, Preschool; Clobazam; Creatinine; Dinoprost; Enzyme-Linked Immunosorbent Assay; Epilepsy; Female; Humans; Linear Models; Male; Oxidative Stress; Predictive Value of Tests; Tobacco Smoke Pollution; Treatment Outcome; Valproic Acid

Pilocarpine (PILO) administered to rats acutely induces status epilepticus (acute period), which is followed by a transient seizure-free period (silent period), and finally by a chronic phase of spontaneous recurrent seizures (chronic period, SRS) that lasts for the rest of animal's life. Hippocampal neurochemical changes following PILO administration include alteration in monoamines and amino acids content during all phases of this epilepsy model. The present work was delineated to study the content of prostaglandins (PG) levels in hippocampus during the three phases of this model. The levels of PG E2, PG F2 alpha and PG D2 were measured by radioimmunoassay 1 h after PILO, 5 h after PILO, during the silent period, and interictally into the chronic period. The results show, in hippocampus of rats, increase of PG F2 alpha and PG D2 during status epilepticus, increase of PG D2 during the silent period and increase of PG E2 and PG D2 during the chronic phase, when compared with control group. These changes match previously reported alteration in monoamines and amino acid levels, showing that altered neurotransmission is accompanied by changes in second messengers and enzyme activity related to PG production during all phases of the epilepsy model.

Topics: Animals; Dinoprost; Dinoprostone; Disease Models, Animal; Epilepsy; Hippocampus; Male; Muscarinic Agonists; Pilocarpine; Prostaglandin D2; Rats; Rats, Wistar; Recurrence; Status Epilepticus

In gerbils pentylenetetrazole- or handling-induced seizures were accompanied by cerebral formation of small amounts of cysteinyl-leukotrienes (LT) but large amounts of prostaglandin (PG) F2 alpha. By contrast, in rats injected with pentylenetetrazole or bicuculline very large amounts of PGF2 alpha but no cysteinyl-LT could be detected in the brain tissues. The data indicate that at least in rats the extensive neuronal activity during tonic-clonic convulsions is not necessarily sufficient for the activation of the 5-lipoxygenase pathway. Apparently important species differences do exist.

Topics: Animals; Bicuculline; Brain; Dinoprost; Epilepsy; Gerbillinae; Handling, Psychological; Kinetics; Pentylenetetrazole; Seizures; SRS-A

Cerebrospinal fluid prostaglandin F2 alpha (CSF PGF2 alpha) levels were measured by radioimmunoassay in children as follows: Febrile convulsions (31 cases), epilepsies (32 cases), meningitides (31 cases) and non-neurological diseases (20 cases), totaling 114 cases. A 4.5-fold increase in CSF PGF2 alpha levels was seen in simple febrile convulsion, and a 2.5-fold increase in those with complex febrile convulsion as compared to those with non-neurological diseases. On the other hand, no increase in CSF PGF2 alpha levels was seen in children with epilepsy. When the body temperature was normal, the mean CSF PGF2 alpha levels showed no relation with age. When the body temperature was between 37.5 degrees C and 40 degrees C, the CSF PGF2 alpha levels in infants were higher than those in older children. The CSF PGF2 alpha levels in children with meningitis were high. The mean CSF PGF2 alpha levels in bacterial meningitis were not statistically (p greater than 0.05) different from those in viral meningitis. The CSF PGF2 alpha levels in meningitis were high on admission and gradually decreased with therapy. The results of our studies indicate that PGF2 alpha of the central nervous system markedly increased in infants and children with febrile convulsions or meningitis but not in those with epilepsy.

Topics: Adolescent; Age Factors; Body Temperature; Child; Child, Preschool; Dinoprost; Epilepsy; Humans; Infant; Infant, Newborn; Meningitis; Prostaglandins F; Seizures, Febrile