Mucuna pruriens seed protects the hippocampal neurons and abrogates seizure indices in chemically-convulsed mice: Evidence of the Nrf2 expression defense pathway.

The anti-convulsant mechanisms and neuroprotective effects of Mucuna pruriens (MP) seed in male BALB/c mice were evaluated. Ninety mice were kindled with picrotoxin, strychnine, or pilocarpine hydrochloride at the 30th minute of intraperitoneal injection (i.p) of normal saline (0.2 ml), MP (200, 100, 50 mg/kg), diazepam (7.5 mg/kg), or haloperidol (5 mg/kg). The onset of convulsion and percentage mortality was recorded. The histoarchitectural and immunohistochemical profiles of the brains were determined. Data were expressed as mean ± SEM with a one-way analysis of variance (ANOVA), while p < 0.05 was considered significant. There was a significant prolongation of the latency to first seizure across the treatment groups following picrotoxin, and pilocarpine-induced convulsion; a decrease in percentage mortality in the MP (50 mg/kg) treatment group, and an increase in the hippocampal nuclear factor erythroid 2-related factor 2 count, and Neu-N expression in the MP (200 mg/kg, and 100 mg/kg) treated mice. Treatment with MP seed may abolish seizure occurrence and consequential mortality; mechanisms traceable to its GABAergic expression and hippocampal NRF 2 and Neu N expression.

Preliminary assessment of proanthocyanidin isolates of Vitis vinifera seed on the central nervous system of male Albino mice.

This study evaluated the potential neurobehavioral effects of proanthocyanidin-rich-fraction (PRF) obtained from Vitis vinifera seed in male Albino mice. Adult (2½- to 3-month old) male Albino mice were treated with PRF (200, 100, 50 mg/kg) and subjected to diverse behavioral models specially designed for the assessment of central nervous system-acting agents. One-shot intraperitoneal (i.p) injection of PRF (200 and 100 mg/kg) decreased the rectal temperature, exploratory activities (locomotion, rearing, and grooming), anxiety-like responses (% open-arm time, open-arm entries but decreased the total number of enclosed arm times). However, acute i.p administration of PRF decreased the total score of apomorphine-induced stereotyped behaviors, latency to hexobarbitone-induced sleep, and increased the total sleep duration. Moreover, indices of convulsion (tonic flexion, extension, clonic convulsion, stupor, and recovery time) were decreased in the PRF treatment groups, especially the PRF (50 mg/kg)-treated mice. Based on these present findings, it could therefore be inferred that systemic administration of PRF of V. vinifera seed origin induces diverse modification on the behaviors of the treated mice stemming from anxiolytic, anticonvulsant, sedative, and decrease in core temperature.

Proanthocyanidin from Vitis vinifera attenuates memory impairment due to convulsive status epilepticus.

This study investigated the effects of proanthocyanidin-rich fraction (PRF) of Vitis vinifera seed extract on the markers of hippocampal-dependent memory in convulsive status epilepticus (CSE) rat model. One hundred juvenile Wistar rats were randomized into 6 groups. Group 1 (n = 10) received propylene glycol (PG 0.1 ml/100 g) intraperitoneally (i.p), while convulsion was induced in groups 2-6 (n = 18 each) using lithium (127 mg/kg i.p) and pilocarpine hydrochloride (40 mg/kg i.p). The established CSE rats in groups 2-6 received a daily treatment of PG (0.1 ml i.p), PRF (30 mg/kg i.p), PRF (20 mg/kg BW i.p), PRF (10 mg/kg BW i.p) or diazepam (5 mg/kg BW i.p) for seven days. Thereafter, they were kept untreated but with access to feed and water for 21 days. The control and CSE-treated rats were subjected to behavioral tests, while the biochemical and histomorphological evaluations of the hippocampus were done after the sacrifice. The results were presented as mean ±â€¯SEM in graphs or tables. The level of significance was considered when p < 0.05. There was significant decrease in the hippocampal-dependent memory, hippocampal weight and an increased malondialdehyde concentration following CSE. The activities of acetylcholinesterase decreased significantly in the PRF-treated CSE rats. The hippocampal glial cells and granule count increased significantly following CSE, with various neurodegenerative features in the CA1 of the hippocampus. These derangements were attenuated significantly following PRF treatment. Memory impairment following CSE may be attenuated with the administration of PRF from V. vinifera seed in rats.

Anticonvulsant and neuroprotective effects of carbamazepine-levetiracetam adjunctive treatment in convulsive status epilepticus rat model: Inhibition of cholinergic transmission.

This study evaluated the anticonvulsant and neuroprotective effects of carbamazepine (CBZ), levetiracetam (LEV), and CBZ + LEV adjunctive treatment in convulsive status epilepticus (CSE) rat model. Twenty-five male Wistar rats were randomized into five groups (n = 5). Groups I and II received 0.2 ml of normal saline intraperitoneally (i.p), while groups III-V received CBZ (25 mg/kg i.p), LEV (50 mg/kg i.p) or combination of sub-therapeutic doses of CBZ (12.5 mg/kg i.p) and LEV (25 mg/kg i.p). Thirty minutes later, seizure was kindled with pilocarpine hydrochloride (350 mg/kg) in group II-V rats. Seizure indices, markers of excitotoxicity, and astroglioses were determined, while the hippocampal morphometry was also evaluated. The data was analysed using descriptive and inferential statistics, while the results were presented as mean ± SEM in graphs or tables, and the level of significance was taken at p < 0.05. The anticonvulsant treatments delayed the inception of seizure indices (p = 0.0006), while the percentage mortality decreased significantly (p = 0.0001) in all the treatment groups. The hippocampal concentrations of acetylcholine, malondialdehyde, and tissue necrotic factor-alpha decreased significantly (p = 0.0077) in all the treated group relative to the positive control. The reactive astrogliosis in the hippocampus (CA 1) increased significantly (p = 0.0001) compared with the control but abrogated in all the treatment groups relative to the positive control. The anticonvulsant and neuroprotective effects are in this order: LEV < CBZ + CBZ < CBZ. The drug efficacy is attributable to the inhibition of cholinergic transmission.

Assessment of the biomarkers of hepatotoxicity following carbamazepine, levetiracetam, and carbamazepine-levetiracetam adjunctive treatment in male Wistar rats.

OBJECTIVE: This study examined some of the biomarkers of hepatotoxicity following chronic treatment with carbamazepine (CBZ), levetiracetam (LEV), and CBZ + LEV adjunctive treatment in male rats. METHOD: Twenty-four male Wistar rats (140-150 g) were randomized into four groups (n = 6) to receive oral dose of normal saline (0.1 mL), CBZ (25 mg/kg), LEV (50 mg/kg) or sub-therapeutic dose of CBZ (12.5 mg/kg) together with LEV (25 mg/kg) for 28 days. Activities of the liver enzymes and oxidative stress markers were determined while liver histomorphology was also carried out. Data were analyzed using descriptive and inferential statistics. The results were presented as mean ± SEM in graphs or tables, while the level of significance was taken at p < 0.05. RESULTS: The activities of alkaline-phosphatase and malondialdehyde concentrations increased significantly in all the drug treatment groups, while the activities of superoxide dismutase decreased significantly following CBZ, and CBZ + LEV treatment. Alanine-aminotransferase activities increased significantly in the CBZ and CBZ + LEV treated rats compared with control. The liver section of CBZ treated rats showed mild vascular congestion. CONCLUSION: None of these AEDs treatment is devoid of hepatotoxicity. However, the adverse effects in CBZ were greater than LEV, or CBZ + LEV adjunctive treatment.

Graded doses of grape seed methanol extract attenuated ataxic movement, cerebellocortical toxicity, and impairment following chronic carbamazepine treatment in male Wistar rats.

This study investigated the effects of chronic cotreatment of carbamazepine (CBZ) with grape seed methanolic extract (GSME) on the markers of neurotoxicity and motor coordination in male rats. Thirty male Wistar rats were randomized into 5 groups (n = 6) and treated orally with propylene glycol (PG 0.1 ml/day), CBZ (25 mg/kg), CBZ (25 mg/kg) + GSME (200 mg/kg), CBZ (25 mg/kg) + GSME (100 mg/kg), or CBZ (25 mg/kg) + GSME (50 mg/kg) for 28 days. Thereafter, the animals were subjected to motor-coordination tests and, eventually, sacrificed by cervical dislocation. The cranium was opened and the brain excised. The prefrontal cortex (PFC) and cerebellum were homogenized for the biochemical assessment, while representative brain was fixed in 10% neutral-buffered formalin for the histomorphological investigation. The results were presented as mean ±â€¯SEM, analyzed using one-way analysis of variance (ANOVA) and Student-Newman-Keuls post hoc analysis where appropriate, while p < 0.05 was considered statistically significant. Indices of motor coordination were significantly (p = 0.0014) impaired with a significant (p = 0.0001) increase in the concentration of malondialdehyde (MDA) in the PFC and cerebellar tissue. In addition, the activities of glutathione increased (p = 0.0001) significantly in the CBZ + GSME-treated rats. All these anomalies were attenuated in the CBZ + GSME treated rats. Coadministration of GSME with CBZ may ameliorate CBZ-induced neurotoxicity, histoarchitectural disorganization of PFC and cerebellum with resultant effect on fine motor actions.

Graded doses of grape seed methanol extract attenuated hepato-toxicity following chronic carbamazepine treatment in male Wistar rats.

AIM: This study investigated the effects of co-administration of carbamazepine (CBZ) with grape (Vitis vinifera) seed methanolic extract (GSME) on liver toxicity. METHOD: Thirty-five male rats (145-155 g) were randomized into 5 groups (n = 7) and administered with propylene glycol (PG 0.1 mL/day), CBZ (25 mg/kg), CBZ (25 mg/kg) + GSME (200 mg/kg), CBZ (25 mg/kg) + GSME (100 mg/kg), or CBZ (25 mg/kg) + GSME (50 mg/kg) orally for 28 days. Twenty-four hours after the last dose, changes in the body weights were determined. The rats were euthanized by cervical dislocation. The liver was weighed and later homogenized; while the supernatant was analyzed biochemically. The liver tissues were preserved in 10 % neutral-buffered formalin for the histomorphological investigation. RESULT: There was significant (p = 0.0001) decrease in the body weight following carbamazepine treatment. The relative liver weight also decreased significantly (p = 0.0004) across the treatment group compared with control. The activities of the liver enzymes (aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and glutathione activities), including the concentrations of malondialdehyde, increased significantly (p ≤ 0.0004) following carbamazepine treatment. Various morphological alterations were observed, especially in the photomicrograph of the CBZ treated rats. However, these derangements were attenuated significantly in the CBZ - GSME co-treated group. CONCLUSION: This study concludes that GSME treatment may serve as a potential therapeutic agent in carbamazepine-induced hepatotoxicity/ dysfunction.

Carbamazepine adversely altered the pituitary-testicular axis with resultant reproductive dysfunctions than levetiracetam or carbamazepine-levetiracetam adjuvant treatment in male Wistar rat.

This study investigated the on-toward reactions of individual or adjunctive treatment with carbamazepine (CBZ) and levetiracetam (LEV) on the pituitary-testicular axis in male rats. Twenty-four male Wistar rats were randomised into 4 groups (n = 6) and received daily intraperitoneal (i.p) treatment of normal saline (0.1 ml/day); CBZ (25 mg/kg i.p); LEV (50 mg/kg i.p); or combination of CBZ (12.5 mg/kg) and LEV (25 mg/kg) for 4 weeks. The serum concentration of luteinising hormone (LH), follicle-stimulating hormone (FSH), and testosterone was determined. Also, the seminal profile and histomorphological status of the testis were determined. Data were analysed using descriptive and inferential statistics. The control and test groups were compared using Student's t test, analysis of variance (ANOVA), and Student-Newman-Keuls post hoc analysis where appropriate, while the results presented as mean ± SEM in graphs or tables. The level of significance was taken at p < .05. The percentage motility, viability, and concentration of FSH decreased significantly in all the treatment groups, while the testis was presented with various forms of histomorphological aberrations. This study concludes that CBZ, and CBZ + LEV adjunctive treatments alter the pituitary-testicular axis with evidence of hormonal deregulation and alteration in the reproductive functions' indices, while LEV treatment remains the safest.

Chronic administration of gabapentin and a gabapentin-carbamazepine combination reversibly suppress testicular function in male Wistar rats (Rattus norvegicus).

The effect of chronic administration of gabapentin, carbamazepine or a gabapentin-carbamazepine combination on testicular function in male rats was investigated to determine the effect of combining reduced doses of anti-epileptic drugs on the management of seizures, particularly with respect to the testis sequellae of chronic anti-epileptic administration. Male rats were randomized into four groups (n=10). Each group received daily intraperitoneal (i.p.) injections for 28days as follows: Group I, normal saline 0.1mL/day; Group II, gabapentin (GBP) 16mg/kg/day; Group III, carbamazepine (CBZ) 20mg/kg/day; and Group IV, sub-therapeutic doses of both GBP (8mg/kg) and CBZ (10mg/kg)/day. Twenty-four hours after the last treatment, five rats from each group were sacrificed and the remaining rats were allowed to recover for another four weeks. Sperm characteristics, serum testosterone, and histological integrity of the testis was assessed 24h after treatment and after 28days of drug withdrawal. GBP, CBZ, and GBP-CBZ combination significantly reduced the absolute weight of the testis, epididymis, and seminal vesicle (p<0.05). Moreover, epididymal sperm count and morphology were significantly decreased (p<0.05) in GBP, CBZ, and GBP-CBZ groups. Reduction in serum levels of testosterone for all of the treated groups was statistically significant (p<0.05). The cytoarchitecture of the testicular tissue in the testis of CBZ and GBP-CBZ groups showed disorganization. The altered testicular function were almost restored in GBP treated rats. CBZ and GBP-CBZ combination have delayed but reversible antifertility in the rats. Hence, chronic administration of GBP, CBZ, and GBP-CBZ combination reversibly reduced testicular function in male rats.