Effects of acute inhibition of fatty acid oxidation on latency to seizure and concentrations of β hydroxybutyrate in plasma of rats maintained on calorie restriction and/or the ketogenic diet

The present study was designed to evaluate the effects of acute inhibition of fatty acid oxidation on plasma levels of P 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 P 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 KID. 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 KID. (C) 2002 Elsevier Science B.V. All rights reserved.