An improved method for toxicological profiling of chemical substances.

Toxicity profiling is an integral part of the drug discovery pipeline. The 3Rs principle-Replacement, Reduction, and Refinement, is considered a golden rule in determining the most appropriate approach for toxicity studies. The acute toxicity study with proper estimate of median lethal dose (LD) is usually an initial procedure for the determination of most suitable test doses for preclinical toxicological and pharmacological profiling.

Mucuna pruriens seed repeals the hypothalamic-pituitary-testicular axis disruption following carbamazepine treatment in male Wistar rats.

This study examined the potential effects of Mucuna pruriens (MP) seed powder on the disruptions of the hypothalamic-pituitary-testicular axis caused by the carbamazepine (CBZ) treatment in male Wistar rats. A total of 35 male Wistar rats were randomized into 5 groups (n=7). The animal in group 1 received normal saline (0.

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.

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.

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.

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.

The impairment of motor coordination following chronic carbamazepine-levetiracetam combination treatment with evidence of corticocerebellar toxicity in male Wistar rats.

This study examined the effects of carbamazepine (CBZ) or levetiracetam (LEV) and sub-therapeutic doses of the combination of the two conventional antiepileptics on some of the markers of motor coordination. Twenty-four male Wistar rats (140 ± 5 g) were randomized into 4 groups (n = 6). Group I rats received physiological saline (0.

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.

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 () 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.

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.

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.

Hypothalamic-pituitary-testicular axis derangement following chronic phenytoin-levetiracetam adjunctive treatment in male Wistar rats.

The effects of phenytoin (PHT), levetiracetam (LEV) or their adjunctive treatment on the hypothalamic-pituitary-testicular axis in male Wistar rats were determined. Twenty-eight male rats (150-180 g) were randomised into four groups (N = 7). Groups I to IV received intraperitoneal treatment of either normal saline (0.

Biochemical, hematological and histopathological evaluation of the toxicity potential of the leaf extract of in rats.

Background And Aim: The many pharmacological potentials of (L.C. Rich) Vahl, especially in managing central nervous system disorders, hypertension, diabetes and infections, have made it a subject of abuse, necessitating the need to ascertain its safety.

Therapeutic Potentials and Cytochrome P450-Mediated Interactions Involving Herbal Products Indicated for Diabetes Mellitus.

Background: There has been an increase in the use of herbal products to complement conventional drugs in the treatment of various diseases especially in developing countries. This may be attributable to the potential cost-effectiveness and ease of accessibility of these products as well as the perception of their safety profiles. However, there are numerous literature reports on herbs altering the pharmacokinetics and pharmacodynamics of other co-administered drugs thereby modulating the therapeutic outcomes.

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.

Caffeine and sleep-deprivation mediated changes in open-field behaviours, stress response and antioxidant status in mice.

Objectives: Effects of daily caffeine consumption on open-field behaviours, serum corticosterone and brain antioxidant levels were investigated after six hours of total sleep-deprivation in prepubertal mice. We tested the hypothesis that daily caffeine consumption may significantly alter behaviour, stress and antioxidative response of prepubertal mice to an acute episode of total sleep-deprivation.

Methods: Prepubertal Swiss mice of both sexes were assigned to two main groups of 120 each (subdivided into 6 groups of 10 each, based on sex), and administered vehicle or graded oral doses of caffeine (10, 20, 40, 80 and 120 mg/kg/day) for 14 days.

Evidence of alterations in brain structure and antioxidant status following 'low-dose' monosodium glutamate ingestion.

Objective: The study investigated the effects of low dose monosodium glutamate (MSG) on the brain, with a view to providing information on its effects on neuronal morphology and antioxidant status in mice.

Methodology: Sixty male mice (20-22 g) were divided into six groups of ten animals each. Vehicle (distilled water), a standard (l-glutamate at 10mg/kg body weight) or MSG (10, 20, 40 and 80mg/kg body weight) were administered orally for 28days.

Foraging enrichment modulates open field response to monosodium glutamate in mice.

Background: Environmental enrichment can enhance expression of species-specific behaviour. While foraging enrichment is encouraged in laboratory animals, its impact on novelty induced behaviour remain largely unknown.

Purpose: Here, we studied behavioural response of mice to acute and subchronic oral monosodium glutamate (MSG) in an open field with /without foraging enrichment.

Caffeine/sleep-deprivation interaction in mice produces complex memory effects.

Background: Sleep deprivation negatively impacts memory, causing deficits in memory processes. Of interest is any agent that can offset such deficits. Mice were given varying doses of caffeine for 14 days and then deprived of sleep for 6 hours by the 'gentle handling' method.

Sedative and anxiolytic effects of the extracts of the leaves of Stachytarpheta cayennensis in mice.

The leaves are used ethnomedicinally in Nigeria and other parts of the world for insomnia and anxiety among other uses. The investigations sought scientific evidence for the ethnomedicinal use of the leaves for the management of insomnia and anxiety as well as the neural mechanisms for the activities. The sedative and anxiolytic effects of the extracts of the leaves of Stachytarpheta cayennensis were examined in this study.

Bronchorelaxant property of 'African potato' (Hypoxis hemerocallidea corm) aqueous extract in vitro.

This study was undertaken to investigate the bronchorelaxant effect of Hypoxis hemerocallidea corm ('African potato') aqueous extract (APE) on spasmogen-provoked contractions of guinea-pig isolated tracheal smooth muscle preparations. APE (25-400 mg/ml) relaxed spasmogen (histamine-, carbachol- and potassium-)-induced contractions of the isolated tracheal muscle preparations in a concentration-dependent manner. The relaxant effects of APE on spasmogen-evoked contractions of the tracheal muscle preparations were not altered by bath-applied propranolol (0.

Hypoglycaemic and hypotensive effects of Momordica charantia Linn (Cucurbitaceae) whole-plant aqueous extract in rats.

Various morphological parts (roots, stems, leaves and fruits) of Momordica charantia Linn (family: Cucurbitaceae) are used traditionally in African folk medicine to manage, control and/or treat a plethora of human ailments, including diabetes mellitus and hypertension. In order to scientifically appraise some of the folkloric, anecdotal and ethnomedical uses of M charantia, the present study was undertaken to investigate the hypoglycaemic and hypotensive effects of M charantia whole-plant aqueous extract (MCE) in rat experimental paradigms. The hypoglycaemic effect of the plant extract was examined in normal and diabetic rats, using streptozotocin (STZ)- induced diabetes mellitus models.