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Advanced Neurology Pantothenic acid in kainic acid-induced epilepsy

KA-induced epilepsy model has been commonly reported and dimethyl sulfoxide (Cat. No. 102952) were purchased
in clinical TLE research . from Sigma Chemical Co. (Sigma, St. Louis, MO, USA).
[5]
The stimulation of an excitatory amino acid receptor has Protease inhibitor cocktail (Cat. No. 78430) was purchased
been reported to cause the production of reactive oxygen from Roche Applied Science (Mannheim, Germany).
species (ROS) . Not only does this pathological loop Enzyme-linked immunosorbent assay kits were obtained
[6]
contribute to the induction of long-lasting seizures, but it from Pierce Biotechnology Inc. (Rockford, IL, USA). All
may also lead to neuronal damage if not treated [7,8] . Status other materials were of the analytical grade.
epilepticus (SE) is an epidemic state where seizures are 2.2. Animals
prolonged and neurological injuries occur in uncontrolled
manner [9,10] . Systemic or intracerebroventricular injection Young Wistar albino mice (3 – 4-weeks-old) of both sexes,
of KA induces SE, which causes nerve cell injury and weighing 20 – 25 g were used in this study. The animals were
damages to various regions of the limbic system . ROS housed in cages with paddy husk bedding that was changed
[11]
appears to be involved in the pathway associated with daily. The mice were kept in a group of six (two males and
the pathogenesis of SE . Several scientific investigations four females) under room temperature (25 ± 1°C) with
[12]
have demonstrated that antioxidants can facilitate the polypropylene cages maintained on a 12-h light-dark cycle.
inhibition of neurotoxicity caused by glutamic agents. The Unrestricted access to water and food was permitted for the
most feasible strategy to determine antioxidant capability mice (standard pallet). All protocols for the experiments
would be to scavenge free radicals using non-enzymatic were approved and implemented according to committee
exogenous antioxidants . guidelines (approval no. CPCSEA/474/2021-08).
[12]
Treatment offered to SE patients includes drugs that 2.3. Experimental design
interfere with inflammatory processes, which alter the KA was administered intraperitoneally (i.p.) to mice at a
expression of interleukin (IL)-1β, tumor necrosis factor dose of 10 mg/kg in a solution maintained at pH 7.2 ± 0.1.
alpha (TNF-α), and IL-6 in in certain brain regions . The Following KA treatment, behavioral changes (grooming,
[13]
results of recent preclinical studies of seizure and primary rearing, and rubbing of the hind paws, urination,
care indicate the potential role of the inflammatory process defecation, moist dog shakes, jaw motions, salivation,
in epilepsy etiopathogenesis [14,15] . Pantothenic acid (PA) is a and head nodding), frequency and delay of seizures,
derivative of β-alanine and is available in the dextrorotatory and survival were monitored in mice and recorded for a
form of calcium salts [16,17] . In humans, deficiency in PA [16]
causes different behavioral symptoms, such as depression, maximum of 4 h . On the last day of the experiment, all
personality changes, frequent infection, fatigue, and sleep mice were euthanized, the blood (serum) was collected,
disturbance, as well as different histological changes in and the tissues were harvested for histological analysis.
tissues leading to cardiac instability, abdominal pain, and The levels of a series of biochemical parameters, such as
muscle weakness [13,18,19] . Studies have also suggested that PA glutathione (GSH), superoxide dismutase (SOD), nitrite,
deficiency causes neurological disturbances . Therefore, catalase, acetylcholine esterase (AChE), MAO-A, and
[20]
the present study was designed to evaluate the effect of PA MAO-B, were determined. The brain TNF-α level was also
on KA-induced SE and the associated neurodegeneration determined to assess the extent of inflammation.
in mice. 2.4. Animal grouping
The anticonvulsant activity of many antioxidant The mice were divided into several groups and treated as
compounds, such as curcumin and vineatrol, has been indicated.
investigated earlier, and we aimed to examine the
anticonvulsant activity of PA using the KA epileptic model. Group 1 serves as the control group and was given 0.9%
Therefore, the purpose of the present study was to evaluate normal saline.
the effect of PA on epileptic status, oxidative stress, and Group 2 serves as the vehicle-treated KA group and was
cognitive impairment in KA-induced mice. In addition, given 10 mg/kg KA i.p. The vehicle (saline 10 mL/kg, i.p.)
we also examined its modulation effects on the release of was administered for 7 consecutive days. KA (10 mg/kg, i.p.)
TNF-α, a proinflammatory cytokine [6,16] . was administered on the 7 day 30 min after the administration
th
of vehicle and animals were observed over a period of 4 h for
2. Materials and methods any change in behavioral parameters, incidence, and latency
2.1. Drugs and chemicals of convulsions.
PA (CAS 79-83-4), KA (CAS 487-79-6), diazepam (CAS Group 3 serves as the positive control group. Diazepam
439-14-5), radioimmuno precipitation assay lysis buffer, (5 mg/kg, i.p.) was administered on the 7 day, followed by
th

Volume 1 Issue 2 (2022) 2 https://doi.org/10.36922/an.v1i2.40