Neurophysiological Studies on the Effect of Acetone on Pentylenetetrazole-Induced Seizure in Rats

Recent interest in the anticonvulsant effects of acetone has stemmed from studies
related to the ketogenic diet (KD). Despite knowledge of acetone's anticonvulsant
properties, the neurochemical basis for this effect is not well known. The present
study aimed to explore the neurochemical basis underlying the anticonvulsant effect
of acetone in pentylenetetrazol (PTZ) - induced convulsions. This was achieved
through determining the neurochemical changes of acetone in pentylenetetrazol
(PTZ) – treated rats. Male adult rats received either saline, acetone (15 m mol/kg
i.p.), PTZ (60 mg/kg, i.p.), or acetone 3 h before PTZ injection. Result showed that the
maximum concentration of acetone reached about 3 h after acetone administration.
Thus, the animals were administered pentylentetrazole three hours after acetone
treatment. Pentylenetetrazole treated rats exhibited epilepsy, increased brain levels of
excitatory amino acids (glutamate and aspartic acids) and decreased levels of
inhibitory amino acid (γ-aminobutyric acid and glycine). In addition,
pentylenetetrazole treatment decreased total antioxidant activity and reduced
glutathione (GSH) in brain. Acetone pretreatment remarkably decreased seizure
incidence rate and increased seizure latency. Moreover, acetone significantly
minimized the disturbing effect of pentylenetetrazole on the redox status and the
balance between excitatory and inhibitory amino acids. The study indicated that the
epilepsy might be mediated, at least partially, through the disturbance in the redox
status and imbalance between excitatory and inhibitory amino acids in the brain.
Moreover, the study indicated that the antiepileptic effect of acetone might be due to
its antioxidant effect and sustaining the balance between excitatory and inhibitory
amino acids. Moreover, the study might recommend the concurrent intake of
ketogenic diets with the conventional antiepileptic drugs. In addition, synthesizing
new chemical entities yielding acetone during its metabolism in the body might
provide new candidates as antiepileptic drugs.