جستجوی مقالات مرتبط با کلیدواژه « pentylenetetrazole » در نشریات گروه « پزشکی »

Valproic acid (VPA) is a well-known antiepileptic drug; however, it has adverse effects on different body organs, particularly as a result of inducing oxidative stress in the liver. Taurine (Tau) is an amino acid prevalent in the brain that possesses anti-tumor, anti-toxic, and antioxidant properties. This study aimed to investigate the potential of the co-treatment of Tau in mitigating the deleterious effects of VPA in pentylenetetrazole (PTZ) epileptic rats.

A total of 42 rats were divided into six groups of seven as follows: control group, PTZ-treated group (single dose, 60 mg/kg intraperitoneally [IP]), VPA-treated group (500 mg/kg IP for 14 days), Tau-treated group (100 mg/kg orally for 28 days), VPA+PTZ group, and Tau+VPA+PTZ group. The liver function, antioxidant status, and lipid profile markers were evaluated spectrophotometrically.

The IP injection of PTZ and VPA elevated aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and gamma-glutamyltransferase levels. These treatments caused negative alterations in protein concentrations, antioxidant status, and lipid profile markers of the rats’ sera. The treatment with Tau+VPA, on the other hand, improved liver function, restored fairly normal total protein and albumin levels, and improved malondialdehyde, glutathione peroxidase, and total antioxidant capacity concentrations. Furthermore, the Tau+VPA treatment significantly controlled total cholesterol, triglycerides, high-density lipoprotein, and low-density lipoprotein levels, compared to the VPA+PTZ treatment.

The treatment with Tau+VPA is highly effective in controlling the unfavorable side effects of VPA in an epileptic rat model.

Epilepsy is a chronic disorder affecting a broad spectrum of individuals. Recently, there has been increased interest in the role of oxidative stress in epilepsy; adjuvant antiepileptic medicines aimed at reducing oxidative stress may serve as a novel therapeutic approach. In the present study, we investigated the effects of zingerone, a phenolic compound, on maximal electroshock (MES) and pentylenetetrazole (PTZ)-induced seizures and oxidant/antioxidant biomarkers in mice.

In the MES model, the first and second groups received saline and phenytoin (25 mg/kg i.p.), respectively. Groups three to five received zingerone (5, 10, and 30 mg/kg). Thirty minutes later, the digital electroconvulsiometer developed seizures. In the PTZ model, the first and second groups received saline, whereas the others received diazepam (3 mg/kg, i.p.) or zingerone (5, 10, and 30 mg/kg). On day five, PTZ (80 mg/kg, i.p.) was administered to all groups. After behavioral experiments, the activity of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT), and the level of thiobarbituric acid reactive substances (TBARS) in the brain tissue of PTZ model mice were measured.

Our findings suggest that zingerone may have anticonvulsant effects by increasing latency and decreasing the duration of clonic convulsion, tonic hindlimb extension, and mortality rate. Additionally, zingerone administration increased SOD and CAT activities and decreased TBARS levels in the brain tissue of PTZ model mice.

This study suggests that zingerone protects against epileptic seizures and alleviates the oxidative stress associated with epilepsy pathogenesis.

Drug-resistant epilepsy is an unmet medical condition that impacts 30% of epileptic patients. Numerous antiseizure drugs have already been developed but they provide only symptomatic relief and do not target the underlying pathogenesis. Preclinical models provide opportunities to gain insights into obscure mechanisms of drug-resistant epilepsy. Current animal models possess lacunae that need rectification and validation to discover novel antiepileptic drugs. The present study aims to validate 3 different doses of phenobarbital at 2 different periods.

Pentylenetetrazole was given at a sub-convulsive dose (30 mg/kg/day/intraperitoneal [IP]) for 28 days to develop kindling in male Wistar rats. Further, kindled rats were divided into the following four groups: Pentylenetetrazole control, pentylenetetrazole and phenobarbital (20 mg/kg), pentylenetetrazole and phenobarbital 40 mg/kg, and pentylenetetrazole and phenobarbital (60 mg/kg). They were assessed on days 14 and 28 post-kindling. Seizure scoring, oxidative stress, phenobarbital plasma levels, and histopathology of hippocampal neurons were analyzed.

The results showed that the combination of pentylenetetrazole and phenobarbital (40 and 60 mg/kg) remarkably decreased seizure score, elucidated higher antioxidant effect, and prevented neuronal injury on day 14, whereas increased seizure score, oxidative stress, and neuronal death was observed with chronic administration of pentylenetetrazole and phenobarbital in kindled rats at day 28. Moreover, phenobarbital levels in blood were significantly increased at day 28 of phenobarbital treatment compared to day 14.

The adapted protocol with phenobarbital 40 mg/kg dose could be of great potential in screening antiseizure drugs in refractory epilepsy.

Oxidative stress has a crucial role in epileptic seizures. Several studies have shown the protective effect of Artemisia absinthium (A. absinthium) against neuronal damage and oxidative stress. In the current research, the effect of A. absinthium on oxidative stress indicators in an animal model of seizure provoked by injecting pentylenetetrazole (PTZ) was estimated in mice. The mice were allocated into the following groups: a control group in which vehicle was administered; PTZ group (a single dose of 100 mg kg-1, ip); and other groups, which daily received 6.25-200 mg kg-1 of the A. absinthium extract during 3 consecutive days before PTZ. The first recorded MCS and minimal clonic seizure and the first generalized tonic-clonic seizure (GTCS) latencies were analyzed. The brain segments, including the cortex and hippocampus of the animals, were then removed and harvested for oxidative stress evaluation. The extract significantly postponed the onsets of the MCS and GTCS when injected before PTZ. The seizure attacks provoked by PTZ also increased MDA in the cortex and hippocampus to levels greater than the control (P<0.001). In addition, the extract had an ameliorative effect on MDA concentration in the cortex and hippocampus (P<0.05-P<0.001). A lower concentration of total thiol was observed in the brain of the PTZ injected mice than the control ones (P<0.01- P<0.001). Pretreatment with the extract corrected the thiol level in the brain tissue (P<0.05- P<0.001). The current research shows that A. absinthium hydro-ethanolic extract has considerable anti-oxidant properties in a PTZ-induced seizure model in mice.

Cognitive deficit is one of the common comorbidity accompanying epilepsy. The present study evaluated the effect of Celastrus paniculatus seed extract on seizure severity and cognitive deficit following the pentylenetetrazole (PTZ)-induced chemical kindling model.

PTZ kindling model was developed by daily administration of the sub-convulsive dose of PTZ 30 mg/kg for four weeks. After four weeks of induction, the following treatment, namely sodium valproic acid (SVA) 200 mg/kg, C. paniculatus 500 mgkg, pergolide 2 mg/kg, C. paniculatus (250 mgkg)+ Pergolide (1 mg/kg), and C. paniculatus (250 mgkg)+ SVA (100 mg/kg) were administered 30 minutes prior to PTZ (30 mg/kg) injection for a period of next 14 days. Neurobehavioral parameters, including superoxide dismutase (SOD), Catalase (CAT), glutathione (GSH), and dopamine levels were assessed and the Morris water maze test (MWM) and Grip strength test (GPS) were performed. Hematoxylin & Eosin (H&E) staining of hippocampal cornu ammonis (CA1), CA2, CA3, dentate gyrus (DG), and frontal cortex was performed.

C. paniculatus (500 mg/kg) alone and in combination ( C. paniculatus (250 mgkg)+ pergolide (1 mg/kg) and C. paniculatus (250 mgkg)+ SVA (100 mg/kg)) significantly (p<0.05) reduced the seizure score, mean latency time, and distance traveled in the MWM. However, no significant effect was seen in GPS. Biochemical analysis showed elevated antioxidant markers, namely GSH, CAT, and SOD, and also elevated dopamine levels. C. paniculatus and its combination also significantly (P<0.05) protected against neuronal loss in the hippocampus and frontal cortex evidenced by H&E staining

C. paniculatus alone and in combination with other agents may have the potential to treat epilepsy and associated cognitive deficits

Edaravone is an anti-stroke medication that may have nitric oxide (NO) modulating properties. This study evaluated the role of NO in the acute and sub-chronic anticonvulsant effects of edaravone in murine models of seizures induced by intraperitoneal (IP) or intravenous (IV) injections of pentylenetetrazole (PTZ) or electroshock (maximal electroshock seizure [MES]). 132 male albino mice were randomly divided into 22 groups (n=6) and given IP injections of vehicle or edaravone either acutely or for eight days (sub-chronically). The seizure was induced by electroshock or PTZ (IP or IV). The following edaravone doses were used: 7.5, 10, 12.5 (acute); 5, 7.5, 10 (sub-chronic) in IP PTZ model; 5, 7.5, 10 in IV PTZ model; and 5, 10 mg/Kg in the MES. To evaluate NO involvement, 216 mice were randomly divided into 36 groups (n=6) and pretreated with vehicle, edaravone, a non-specific nitric oxide synthase (NOS) inhibitor: N(ω)-nitro-L-arginine methyl ester (L-NAME) (5 mg/Kg), a specific nNOS inhibitor: 7-nitroindazole (7-NI) (60 mg/Kg), or a combination of edaravone plus L-NAME or 7-NI, either acutely or for eight days before seizure induction. Doses of edaravone were as follows: in IP PTZ model: 12.5 (acute) and 10 (sub-chronic); in IV PTZ model: 10; and in the MES: 5 mg/Kg. Data were analyzed using the one-way analysis of variance (ANOVA) followed by Tukey’s test (SPSS 18). P≤0.05 was considered statistically significant. In the IP PTZ model, edaravone increased time latencies to seizures (P<0.001), prevented tonic seizures, and death. Edaravone increased the seizure threshold (P<0.001) in the IV PTZ model and shortened the duration of tonic hind-limb extension (THE) in the MES model (P<0.001). In comparison to mice treated with edaravone alone, adding L-NAME or 7-NI reduced seizure time latencies (P<0.001), reduced seizure threshold (P<0.001), and increased THE duration (P<0.001). Edaravone (acute or sub-chronic) could prevent seizures by modulating NO signaling pathways.

The mechanisms behind seizure suppression by deep brain stimulation (DBS) are not fully revealed, and the most optimal stimulus regimens and anatomical targets are yet to be determined. We investigated the modulatory effect of low-frequency DBS (L-DBS) in the ventral tegmental area (VTA) on neuronal activity in downstream and upstream brain areas in chemically kindled mice by assessing c-Fos immunoreactivity.

In this experimental study, 4-6 weeks old BL/6 male mice underwent stereotaxic implantation of a unilateral stimulating electrode in the VTA followed by pentylenetetrazole (PTZ) administration every other day until they showed stage 4 or 5 seizures following 3 consecutive PTZ injections. Animals were divided into control, sham-implanted, kindled, kindled-implanted, L-DBS, and kindled+L-DBS groups. In the L-DBS and kindled+L-DBS groups, four trains of L-DBS were delivered 5 min after the last PTZ injection. 48 hours after the last L-DBS, mice were transcardially perfused, and the brain was processed to evaluate c-Fos expression by immunohistochemistry.

L-DBS in the VTA significantly decreased the c-Fos expressing cell numbers in several brain areas including the hippocampus, entorhinal cortex, VTA, substantia nigra pars compacta, and dorsal raphe nucleus but not in the amygdala and CA3 area of the ventral hippocampus compared to the sham group.

These data suggest that the possible anticonvulsant mechanism of DBS in VTA can be through restoring the seizure-induced cellular hyperactivity to normal.

The plant Bombax costatum (BC) has been used traditionally in Nigeria for the management of various ailments. The chloroform extract of BC bark was investigated for its potential effects against the induced seizures and depression in rats.

Thirty Wistar rats were divided into five groups of six. Group I received normal saline, group II received pentylenetetrazole (PTZ, 35 mg/kg), group III received diazepam (5 mg/kg) plus PTZ at 35 mg/kg, group IV received 250 mg/kg of the BC extract, and group V received 500 mg/kg of the same extract. The above protocol was repeated on alternate days from the first to twenty 5th days. 

Tukey’s post hoc test revealed a statistically significant increase in the seizure scores after using PTZ (3.38±0.29, P<0.0001), in contrast to a decrease in the seizures after treatment with the BC extract (250 mg/kg; 2.72±0.25, P=0.0001). The analysis of variance for forced swimming test showed a significant decrease in immobility time if treatment with the extract (250 mg/kg; 125±5.59; P=0.01). The immobility duration increased with the PTZ treatment (163.8±12.03). The brain’s dopamine and serotonin levels under PTZ effect significantly decreased to 140.2±15.66 and 26.38±1.16, respectively, when the rats were treated with the extract at 500 mg/kg. 

The findings of this study suggest that the BC extract has anticonvulsive and anti-depressive properties, thus it offers neuro-protection against both conditions, induced by PTZ in rats.

Epilepsy as a neurological disorder is characterized by unpredictable and periodic seizures. In the present study, the anticonvulsant effect of different doses of salep hydroalcoholic extract on pentylenetetrazole (PTZ) induced seizures was investigated.

Methods and Materials/Patients: 

The animal model of seizure was established by the intraperitoneal injection of pentylenetetrazole (PTZ- 85 mg/kg). Hydroalcoholic extract of salep was administered to the animals in 3 doses (80, 160, and 320 mg/kg). The parameters of the onset and duration of tonic-clonic seizure, total seizure time, balance (falling), and jumping during seizure mortality rate were measured. The results were analyzed by ANOVA test at a significant level of p≤0.05.

The results of the current study indicated that salep extract increased the delay in the onset of seizure in the PTZ + extract group in comparison with the PTZ group. The duration of tonic-clonic seizure and the number of falling, jumping, and total seizure times were significantly decreased by salep extract compared to the PTZ group. In the seizure + salep extract, the number and percentage of 24-hour mortality among animals decreased with increasing dosage. All changes were dose-dependent and 320 mg/kg showed the most effect.

  Extract of salep can probably have anticonvulsant properties, however, further studies are needed to clarify the exact mechanisms.

Piracetam and octreotide as nootropic and neuroprotective medicines were used in the epileptic rats to evaluate their impacts on the hippocampal expression of BAX and BCL2 genes.
Six experimental groups of adult rats were pretreated for 7 days as follows: two piracetam groups (30 and 100 mg/kg/day), two octreotide groups (50 and 100 mg/kg/day), positive control group (injected with diazepam, 2 mg/kg, single dose before pentylenetetrazole injection) and negative control group (injected with normal saline). Seizures were induced with a single injection of pentylenetetrazole (PTZ, 60 mg/kg) after pretreatments. Signs of resulted seizures were classified according to the Racine scale. The BAX and BCL2 transcripts were measured in the hippocampus by quantitative real-time PCR.
A delayed onset time of the seizures (stage 1 of Racine scale) and shorter time of the tonic-clonic seizures (stage 5 of Racine's scale) were observed in the piracetam and octreotide groups as compared to negative control group (P<0.05). The BAX transcript was higher in the positive control and octreotide (100 mg/kg) groups than other groups (P<0.05). The BCL2 transcript was higher in the positive control, piracetam (100 mg/kg) and octreotide (100 mg/kg) groups than the negative control group (P<0.05). The BAX/BCL2 ratio was lower in the positive control and piracetam (30 and 100 mg/kg) groups than other groups (P<0.05).
BAX/BCl2 ratio as an indicator of progressive apoptosis was attenuated by the piracetam in the hippocampus of epileptic rats while useful effects of the octreotide are independent of BAX/BCl2.

Neuroprotective and antioxidant effects of Ocimum basilicum (O. basilicum) against pentylenetetrazole (PTZ)-induced seizures were investigated. 

Mice were divided as follows: (Group 1) Control, (Group 2) PTZ, (Groups 3-5) 50,100 and 200 mg/kg hydro-ethanolic (HE) extract, and (Groups 6-8) 200 mg/kg ethyl-acetate (EAF), N-hexane (NHF) and water (WF) fractions. Minimal clonic seizures (MCS) and generalized tonic-clonic seizures (GTCS) latencies were measured. Biochemical and histological studies were done.

MCS and GTCS latency in HE groups were longer than the PTZ group (p<0.05 to p<0.001). EAF and NHF prolonged the onset of MCS and GTCS (p<0.001). PTZ increased malondialdehyde (MDA) and dark neuron (DN) production while decreased thiol, catalase (CAT) and superoxide dismutase (SOD) (p<0.05 to p<0.001).  Pre-treatment by HE and all fractions of the plant attenuated MDA and DN while increased thiol, CAT and SOD (p<0.01 to p<0.001).

EAF and NHF had anticonvulsant properties. The extract and fractions protected the brain from PTZ-induced oxidative damages and showed neuroprotective effects.

Epilepsy is a neurological disorder causing brain dysfunctions. Treatment and control of epilepsy have long been a challenge in medical sciences. Despite the variety of current anticonvulsant drugs, research continues to discover new drugs with the highest efficacy and the lowest side effects. In the present study, the anticonvulsant effects of anethole in the seizure induction with pentylenetetrazole (PTZ) were evaluated in a mice model with respect to its possible antioxidant effects. PTZ is known to cause generalized epilepsy in animal models. Accordingly, in this experimental study, 40 mice were divided into 5 groups; the first group received normal saline, the second group received 10 mg/kg diazepam, and the third to fifth groups were given anethole at 31.25, 62.5 and 125 mg/kg, respectively. Injections were conducted intraperitoneally for one week; then seizures were induced by the intravenous injection of 90 mg/kg PTZ. After determination of the duration of seizures in different groups, the mice were finally placed under deep anesthesia and their prefrontal cortex tissue was isolated to measure nitric oxide (NO), antioxidant capacity and malondialdehyde (MDA) concentrations. The results showed that anethole increased the delay in the onset of seizures, decreased the amount of nitrite in the brain, enhanced antioxidant capacity, and reduced MDA content in a dose-dependent manner. Overall, our results indicated the anticonvulsant effects of anethole that could be mediated by inhibiting oxidative stress.

Seizure is due to the abnormal electric activity of neurons in the brain. Because of the side effects of synthetic drugs, plant medicines can be used instead to control seizures. 

This study aimed to investigate the effect of aerobic exercise and α-pinene on pentylenetetrazole-induced seizures in mature male rats.

A total of 40 Wistar male rats (weight: 200-250 g) were divided into five groups: control (receiving normal saline), positive control (receiving 1 mg/kg diazepam as an antiepileptic drug), aerobic exercise (receiving five sessions of exercise per week, each session for 30 min), α-pinene (receiving 200 mg/kg for 4 weeks), and aerobic exercise plus α-pinene. Thirty minutes after the intervention, 85 mg/kg Pentylenetetrazole (PTZ) was intraperitoneally administered to the rats in all experimental groups, and their seizure-related behaviors were observed and recorded.

Combined use of α-pinene and aerobic exercise significantly increased the delay of onset of seizure (P<0.05) and decreased the duration of the tonic-clonic seizure (P<0.001) and the total duration of seizure P<0.001) compared to the control group.

The findings showed that the use of α-pinene together with exercise can have preventive effects against pentylenetetrazole-induced seizures in mature male rats through their antioxidant activity.

The effects of Cinnamomum zeylanicum on oxidative stress imposed by pentylenetetrazole (PTZ) was examined in mice brain tissues. Animals were divided into five groups as follows: 1- control group which received saline; 2- PTZ group (100 mg/kg, ip); and groups 3 to 5 which received (100, 200, and 400 mg/kg) of C. zeylanicum for seven days prior to PTZ injection. The latencies of the first minimal clonic seizure (MCS) and the first generalized tonic-clonic seizure (GTCS) and levels of oxidant and antioxidant biomarkers were measured. Treatment with the two higher doses of the extract significantly increased the MCS and GTCS latencies (p<0.05 to p<0.001). Malondialdehyde (MDA) and nitric oxide (NO) levels were increased, but superoxide dismutase (SOD), catalase (CAT), and thiol were decreased in both cortical and hippocampal tissues of the PTZ group compared to the controls (p<0.001). Pretreatment with the two higher doses of C. zeylanicum significantly led to a significant correction in NO, MDA, SOD and CAT levels in the hippocampus and cortex compared to the PTZ group (p<0.05 to p<0.001). Antioxidant and anticonvulsant effects of C. zeylanicum in PTZ-injected animals may suggest its potential therapeutic effect on nervous diseases such as seizures.

Epilepsy is one of the most common neurological disorders. Though there are several effective drugs for treating epilepsy, most drugs are associated with side effects and drug interactions. Stachys lavandulifolia used in Iranian traditional medicine has proven anti-anxiety and sedative properties. The current study aimed to evaluate the anticonvulsant effect of hydroalcoholic extract of S. lavandulifoliaon the Pentylenetetrazole (PTZ)-induced seizure in male mice and the role of benzodiazepine and opioid receptors. 

This study was conducted on 100 male mice, randomly categorized into 10 groups: Normal Saline (NS), two diazepam groups (0.025 and 0.1 mg/kg), three S. lavandulifolia extract groups (50, 100, and 200 mg/kg), diazepam 0.025 mg/kg+S. lavandulifolia extract 50 mg/kg, and three groups that pretreated with NS, flumazenil, or naloxone, 5 min before injection of 200 mg/kg S. lavandulifolia extract. After 30 min, PTZ (80 mg/kg) was injected into animals, and seizure indices were evaluated. 

The S. lavandulifoliaextract attenuated the PTZ-induced seizures in a dose-dependent manner, and pretreatment with flumazenil reversed this effect. However, pretreatment with naloxone could not reverse this effect because seizure indices in the naloxone pretreated group were lower than that in the normal saline group. The combination of an ineffective dose of diazepam and S. lavandulifoliaextract decreased PTZ-induced seizures. 

The results of our study showed the anticonvulsant properties of hydroalcoholic extract of S. lavandulifolia. These effects might be due to the impact of the components of this extract on the central benzodiazepine system.

This study evaluated the anticonvulsant activity of the add-on Drimia maritima (squill) oxymel, used traditionally in the treatment of convulsion, in animal model.

Albino mice pretreated with squill oxymel in different doses of 50, 100, 200 and 400mg/kg by oral gavage, 15min prior to injection of pentylenetetrazole (PTZ). Animals pretreated with flumazenil to determine the mechanism of anticonvulsant action. The total flavonoid content of squill oxymel was also determined.

Squill oxymel prolonged the onset of seizures and decreased the duration of seizures compared to control group. Diazepam used as a reference drug for its anticonvulsive effects, showed complete inhibition of seizure. This study revealed that squill oxymel has significant anticonvulsant effect in PTZ-induced seizures in mice and these effects may be related to its effect on benzodiazepines’ receptors on GABA complex.

These results confirmed the traditional use of squill oxymel in Iranian traditional medicine for treatment of epilepsy. The clarification of mechanisms involved needs further studies.

Along with industrial development and the increasing social complexity of societies, anxiety is one of the most prevalent psychological disorders. Medicinal plants are considered as an enrichment source of ingredients with biological activity. 

The aim of this study was to evaluate the anxiolytic effect of Anethum Graveolens seed (AGS) and the possible involvement of Gamma-Aminobutyric Acid (GABA)-ergic system in the AGS effect.

In the present experimental study, 64 female Wistar rats were divided into eight groups and received various concentrations of hydroalcoholic extract of AGS. To measure the level of anxiety, an elevated plus maze was used in a way that the animal’s head turned to an open arm. Prior to the injections of AGS extract, the GABA receptor antagonist was used. The results were analyzed by one-way analysis of variance using IBM SPSS v. 16.

Dose-response experiments showed that the AGS extract significantly decreased the anxiety indices compared to the control group (P<0.05). To analyze locomotor activity, our data showed that AGS extract at 0.1, 1, and 10 mg/kg could significantly increase locomotor activity compared to the control group (P<0.001). Pentylenetetrazol (PTZ (+extract significantly decreased the anxiolytic effect of AGS extract (P<0.01). 

Considering the anti-anxiety effects of AGS extract and a reduction in this effect caused by PTZ, part of the anti-anxiety effect of extract might be assumed via its interaction with GABA-ergic receptors. Further experimental trials; however, are required for the establishment of the anti-anxiety impact of AGS.