Seizure-induced changes in energy metabolites and effects of N-tert-butyl-alpha-phenylnitrone (PNB) and vitamin E in rats.
Impaired energy metabolism may play a critical role in the neuronal injury caused by kainic acid (KA) induced status epilepticus (SE). Following an acute dose of KA (15 mg/kg, s.c.) rats developed SE within 1 h. Rats were sacrificed 1 or 72 h after the onset of SE using a head focused microwave technique and the brain regions (pyriform cortex, amygdala, and hippocampus) were assayed for energy metabolites: ATP, ADP, AMP, phosphocreatine (PCr) and creatine (Cr) using reversed-phase HPLC (RP-HPLC). Control values were significantly higher in cortex (23-32%) than in other brain regions. Within 1 h, SE caused a marked decline in ATP (44-56%), PCr (49-64%), total adenine nucleotides (TAN, 45-50%) and total creatine compounds (TCC, 32-51%). Within three days, the hippocampus showed the greatest recovery, as the reduced values returned to normal. Pretreatment of rats with an antioxidant (PBN, 200 mg/kg, i.p., 30 min prior to KA; or vitamin E (Vit-E), 100 mg/kg, i.p./day for 3 days), which did not prevent seizure activity, attenuated depletion of high-energy phosphates caused by KA. These findings suggest that the depletion of energy metabolites caused by KA-induced seizures may be linked to oxidative stress mediated toxicity.
Gupta
R C
RC
Murray State University, Hopkinsville, KY 42241, USA.
Milatovic
D
D
Zivin
M
M
Dettbarn
W D
WD
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001921:Brain / Q000378:metabolism; D003497:Cyclic N-Oxides; D004734:Energy Metabolism / Q000187:drug effects*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D007608:Kainic Acid / Q000494:pharmacology; D008297:Male; D009589:Nitrogen Oxides / Q000494:pharmacology*; D010710:Phosphates / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013226:Status Epilepticus / Q000139:chemically induced / Q000378:metabolism*; D014018:Tissue Distribution; D014810:Vitamin E / Q000494:pharmacology*
D000975:Antioxidants; D003497:Cyclic N-Oxides; D018690:Excitatory Amino Acid Agonists; D009589:Nitrogen Oxides; D010710:Phosphates; D014810:Vitamin E; C029217:phenyl-N-tert-butylnitrone; D007608:Kainic Acid