Page 13 - AN-1-2

Advanced Neurology Pantothenic acid in kainic acid-induced epilepsy

Stress and free radicals have been reported to excite KA-induced animals are an accepted preclinical model
excitatory receptors, leading to a transition between seizure for studying neurological disorders, such as epilepsy,
phases [27,28] . In this study, KA induced behavioral changes Huntington’s chorea, and Alzheimer’s disease, which
and seizures in all mice. Compared with KA treatment, pre- involve excitotoxicity and inflammation. PA treatment at
treatment with different doses of PA delayed the initiation 30 mg/kg (i.p.) showed no effect on TNF-α levels, whereas
of seizures and improved memory retention. Furthermore, 60 and 90 mg/kg (i.p.) significantly attenuated the increase
i.p. pre-treatment with PA (30, 60, and 90 mg/kg) of brain TNF-α levels (P < 0.001) in the PA + KA groups
protected mice against KA-induced neurodegeneration. In compared with that in the KA-induced group. In the
the KA-treated group, GSH content declined dramatically, previous studies, PA has also been reported to attenuate
indicating the development of oxidative stress. TNF-α levels, inhibit inducible nitric oxide synthase
PA (90 mg/kg) treatment contributed to more (iNOS) expression, and suppress apoptosis through its
[39]
significant effects on MDA and GSH levels than KA anti-inflammatory activity . The latter effect could, at
treatment alone. Elevated MDA content is an indicator of least in part, explain the beneficial effects of PA on diseases
[40]
free radical production. The PA-treated groups (Groups 3, involving inflammation . These effects are mediated by the
inhibition of nuclear factor kappa B (NF-κB) activation .
[27]
4, and 5) showed a greater increase in the GSH content Cyclooxygenase 2 (COX-2), the inducible isoform expressed
than the KA-treated group did. GSH interacts with free at the injury or inflammatory sites and the central nervous
radicals and can shield cells from the effects of singlet system, plays a significant role in neurodegeneration linked
oxygen, hydroxyl radicals, and superoxide. GSH is the to increased excitatory activity .
[28]
most common intracellular thiol and low-molecular-
weight tripeptide present in cells [28,29] . The inhibition of Glutamate, an active N-methyl-D-aspartate (NMDA)
KA-induced reduction of GSH levels by PA suggests that it receptor excitatory neurotransmitter, increases the
improves the endogenous protective potential of the brain expression of COX-2 and results in higher prostaglandin
against KA-induced oxidative stress . synthesis (unpublished observations). This result was
[30]
confirmed in studies by Vanamala et al. who reported
[29]
PA has been hypothesized as an agent for preventing
mitochondrial damage by modulating lipid peroxidation, that PA decreased the levels of iNOS and COX-2 by
. In view of the above
inhibiting NF-κB activation
[20,33]
thereby conferring neuroprotection [31,32] . This indicates findings, it may be fair to conclude that the antiepileptic
that PA helps minimize mitochondrial oxidative stress. activities of PA are mediated by its significant antioxidant
When the threshold value of excitation is crossed after and anti-inflammatory effects.
administration of KA, animals will experience seizures. The
administration of KA activates glutamate receptors to boost In this study, KA administration resulted in seizures
ROS, thus increasing glutaminergic activity. PA has been related to cognitive dysfunction, as shown by the decrease
reported to modulate glutamatergic activity . The extent in the passive avoidance behavior of retentive latency. The
[33]
to which minimizing the work is difficult to predict, but the results were similar to those of the previous studies that
disruptive chain is noticeable, which reduces excitotoxicity demonstrated cognitive damage and epilepsy following KA
and, hence, demonstrates a defensive effect [20,34,35] . administration [38-40] . The disease progression of seizures,
indicated by increased retention latency in the passive
Therefore, it is difficult to rule out the dual effects of avoidance test following 7 consecutive days of treatment,
PA as an antioxidant and an anti-excitotoxic agent. The leads to cognitive deficits. There is uncertainty about the
change in neurological conditions is also correlated with degree of cognitive dysfunction, which is a limitation
the occurrence of inflammation in neuronal cells . associated with all major antiepileptic drugs .
[20]
[36]
especially in the prognosis of epilepsy and SA . Higher
[36]
levels of cells (such as microglia), effects (such as astrocyte The present study has shown the beneficial effect of PA
activation), and production of cytokines (such as TNF-α, on reducing seizures and cognitive impairment induced
IL-1β, IL-6, and related molecules) have been reported by KA. Thus, PA has the potential to be utilized in clinical
in the process of inflammation in clinical and preclinical SE management. Furthermore, this study shows that PA
models of epilepsy [37,38] . These cytokines are actively could prevent cognitive impairment and serve as a useful
involved in immune protection in the central nervous conventional antiepileptic treatment.
system. Compounds such as PA and other vitamins have
rich antioxidant activities that affect the function of 5. Conclusions
microglia. Cytokines such as TNF-α, IL-1, and IL-1β are This pharmacological study demonstrated that PA has
directly involved in stress, over-firing of signals in seizures, major anti-inflammatory, antioxidant, and neuromodulator
and prolongation of disease stage . activities against epilepsy induced by KA in mice.
[37]

Volume 1 Issue 2 (2022) 7 https://doi.org/10.36922/an.v1i2.40