The present study was designed to evaluate the effects of acute inhibition of
fatty acid oxidation on plasma levels of
beta hydroxybutyrate and latency to PTZ-induced
seizures in ad libitum- (AL), calorie-restricted normal rodent chow- (CR), and calorie-restricted
ketogenic diet (KD)-fed young rats. Young (day 23) Sprague-Dawley rats were fasted for 8 h and then fed their respective diets for 21 days. On day 21 of the diet rats in each group received either saline or the
fatty acid oxidation inhibitor mercaptoacetate (MA; 46 mg/kg intraperitoneally (i.p.). Two hours later, all rats received
pentylenetetrazole (PTZ; 10 mg/kg; i.p.) every 10 min until seizure onset. Results demonstrated that KD-fed rats had the longest (P<0.05) latency to PTZ-induced
seizures. KD-fed rats administered an acute dose of MA had lower (P<0.01) levels of
beta hydroxybutyrate in plasma and shorter latency to PTZ-induced
seizures compared with control KD-fed rats. However, there was not a significant positive correlation (P>0.10) between plasma
beta hydroxybutyrate and latency to seizure, suggesting that
beta hydroxybutyrate may be indirectly involved in the antiseizure effects of the KD.
Fatty acid oxidation inhibition represents an experimental manipulation that may allow for more precise establishment and evaluation of levels of
beta hydroxybutyrate in plasma necessary for antiseizure effects of the KD.